39a Bombay St, Ngaio, Wellington 6035, NZ

+64221998782

©2019 by Dr. Keryn Johnson (THE QUANTUM BIOLOGIST). Proudly created with Wix.com

Life of pie - electrons that is!

Tyrosine absorbance and emission profile emission around 310 nm. Absorption in the UV. Amide bond absorbs at 215nm. UVC is absorbed by all bonds into Sp2 orbital electrons. Human biosynthesis pathway for trace amines and catecholamines.

L-Phenylalanine

L-Tyrosine

L-Dopa

Epinephrine

Phenethylamine

p-Tyramine

Dopamine

Norepinephrine

N-Methylphenethylamine

N-Methyltyramine

p-Octopamine

Synephrine

3-Methoxytyramine

AADC

AADC

AADC

PNMT

PNMT

PNMT

PNMT

AAAH

AAAH

COMT

DBH

DBH

N-methylphenethylamine, an endogenous compound in humans,[4]  is an isomer of amphetamine with the same biomolecular targetTAAR1, a  G protein-coupled receptor which modulates catecholamine neurotransmission.

Transition metals have the ability to share electron density with π-systems through d-orbitals, creating bonds that are highly covalent in character and cannot be modeled as a cation-π interaction. So positively charged acetylcholine and other quaternary substituted amines which are positively charged are able to act as a ligand for the pie electrons in the aromatic ring.

 

Factors influencing the cation–π bond strength. Several criteria influence the strength of the bonding: the nature of the cation, solvation effects, the nature of the π system, and the geometry of the interaction. Nature of the cation

From electrostatics (Coulomb's law), smaller and more positively charged cations lead to larger electrostatic attraction. Since cation- π interactions are predicted by electrostatics, it follows that cations with larger charge density interact more strongly with π systems. The following table shows a series of  Gibbs free energy of binding between benzene and several cations in the gas phase.[2][6]  For a singly charged species, the gas-phase interaction energy correlates with the ionic radius,    (non-spherical ionic radii are approximate).

The pi bond interactions with lithium are the strongest and therefore lithium would have a higher affinity for binding to the aromatic rings of neurotransmitters.

This trend supports the idea that Coulombic forces play a central role in interaction strength since for other types of bonding one would expect the larger and more polarizable ions to have greater binding energies. 

Iron-56: 30 Neutrons and 26 protons, Spin 0+, excess energy -60601.003± 1.354  keV, binding energy 492253.892± 1.356 keV.

binding energy per nucleon of common isotopes; iron-56 labeled at the curve's crest. Iron-55  or  55Fe is a  radioactive isotope of iron with a  nucleus containing 26  protons and 29  neutrons. It decays b  electron capture to manganese-55  and this process has a half-life of 2.737 years. The emitted X-rays can be used as an X-ray source for various scientific analysis methods, such as  X-ray diffraction. Iron-55 is also a source for  Auger electrons, which are produced during the decay. The photo-Fenton reaction of iron-55 allows the rapid production of Mn-55. iron-55 decays via electron capture  to  manganese-55  with a half-life of 2.737 years.[1]  The electrons around the nucleus rapidly adjust themselves to the lowered charge without leaving their shell, and shortly thereafter the vacancy in the K shell left by the nuclear-captured electron is filled by an electron from a higher shell. The difference in energy is released by emitting  Auger electrons  of 5.19 keV, with a probability of about 60%,  K-alpha-1  X-rays  with energy of 5.89875 keV and a probability about 16.2%,  K-alpha-2  X-rays  with energy of 5.88765 keV and a probability of about 8.2%, or  K-beta  X-rays  with nominal energy of 6.49045 keV and a probability about 2.85%. The energies of these X-rays are so similar that they are often specified as mono-energetic radiation with 5.9 keV photon energy. Its probability is about 28%.[2]  The remaining 12% is accounted for by lower-energy Auger electrons and a few photons from other, minor transitions. The K-alpha X-rays emitted by the  manganese-55  after the electron capture have been used as a laboratory source of X-rays in various  X-ray scattering techniques. The advantages of the emitted X-rays are that they are monochromatic and are continuously produced over a years-long period.[3]  No electrical power is needed for this emission, which is ideal for portable X-ray instruments, such as  X-ray fluorescence instruments.[4]  The ExoMars mission of  ESA  is planned to use, in 2018,[5][6]  such an iron-55 source for its combined  X-ray diffraction/X-ray fluorescence spectrometer. 

The 2011 Mars mission  MSL  used a functionally similar spectrometer, but with a traditional, electrically powered X-ray source.[8]

The Auger electrons can be applied in electron capture detectors for gas chromatography. The more widely used  nickel-63  sources provide electrons from beta decay.[3]

K-alpha lines are lenses around the hydroxyl radical 0.097 nm to produce double the eV value around 12470 eV. 

Iron-55 is most effectively produced by irradiation of iron with neutrons. The reaction (54Fe(n,γ)55Fe and  56Fe(n,2n)55Fe) of the two most abundant isotopes  iron-54  and  iron-56  with neutrons yields iron-55. Most of the observed iron-55 is produced in these irradiation reactions, and it is not a primary fission product.[9]  As a result of atmospheric nuclear tests in the 1950s, and until the test ban in 1963, considerable amounts of iron-55 have been released into the biosphere.[10]  People close to the test ranges, for example, Iñupiat(Alaska Natives) and inhabitants of the  Marshall Islands, accumulated significant amounts of radioactive iron. However, the short half-life and the test ban decreased, within several years, the available amount of iron-55 nearly to the pre-nuclear test levels.[10][11]

Where do the neutrons come from? Quantum tunnelling of hydrogen was a proton and an electron combine to produce a neutron. UVA light and photo-Fenton reaction production of neutrons via water splitting and quantum tunneling and the production of hydrides (H-). So UV generates a range of high energy species in water including the hydroxyl radical, hydrogen peroxide and the hydride especially accelerated when photon capture can occur due to phenolics and mineral coordination chemistry via pie bonds. That is why the subconscious mind is using photons of light and is quantum in nature. The temporal and spatial relationships responsible for the high energy species that cannot be seen with the naked eye but are present provides an understanding of the nature of the quantum field inherently present throughout space. 

Of all nuclides, iron-56 has the lowest mass per nucleon. With 8.8  MeV  binding energy per nucleon, iron-56 is one of the most tightly bound nuclei.[1]

Lithium has 1S2, 2S1 Li+ small radi so strong –ve delta G binding on the aromatic ring. So this is the reason for the mood stabilizing effect of lithium because of serotonin and dopamine being the pleasure-based neurotransmitters and 

Li 6/3 and Li 7/3 are both stable forms of the lithium isotope. They do not perform K+ electron capture (capture of a photon despite a strong molecular interaction with Pi electrons.

  Georges, Audi (2003). The NUBASE Evaluation of Nuclear and Decay Properties.  Nuclear Physics A  (Atomic Mass Data Center)  729: 3–128.  Bibcode:2003NuPhA.729....3Adoi:10.1016/j.nuclphysa.2003.11.001.

Jump up^  Esam M. A. Hussein (2003).  Handbook on radiation probing, gauging, imaging and analysis. Springer. p.  26.  ISBN  978-1-4020-1294-5.

Jump up to:a  b  Preuss, Luther E. (1966). Demonstration of X-ray Diffraction by LiF using the Mn Kα X-rays Resulting From  55Fe decay.  Applied Physics Letters  9  (4): 159.  Bibcode:1966ApPhL...9..159Pdoi:10.1063/1.1754691.

Jump up^  Himmelsbach, B. Portable X-ray Survey Meters for  In Situ  Trace element Monitoring of Air Particulates.  Toxic Materials in the Atmosphere, Sampling and Analysis.  ISBN  978-0-8031-0603-1.

Jump up^  The ESA-NASA ExoMars Programme Rover, 2018 . ESA. Retrieved  2010-03-12.

Jump up^  The ExoMars instrument suite. ESA. Retrieved  2010-03-12.

Jump up^  Marinangeli, L.; Hutchinson, I.; Baliva, A.; Stevoli, A.; Ambrosi, R.; Critani, F.; Delhez, R.; Scandelli, L.; Holland, A.; Nelms, N.; Mars-Xrd Team (March 12–16, 2007).  A European XRD/XRF Instrument for the ExoMars Mission. 38th Lunar and Planetary Science Conference. League City, Texas. p.  1322.

Jump up^  Chemistry & Mineralogy (CheMin), NASA

Jump up^  Preston, A. (1970). Concentrations of iron-55 in commercial fish species from the North Atlantic.  Marine Biology  6  (4): 345.doi:10.1007/BF00353667.

Jump up to:a  b  Palmer, H. E.; Beasley, T. M. (1965). Iron-55 in Humans and Their Foods .  Science  149  (3682): 431–2.Bibcode:1965Sci...149..431Pdoi:10.1126/science.149.3682.431PMID  17809410.

Jump up^  Beasley, T. M.; Held, E. E.; Conard, R. M.E. (1965). Iron-55 in Rongelap people, fish and soils.  Health Physics  22  (3): 245–50.doi:10.1097/00004032-197203000-00005PMID  5062744.

In  chemistry,  π-effects or π-interactions  are a type of non-covalent interaction that involves  π systems. Just like in an electrostatic interaction where a region of negative charge interacts with a positive charge, the electron-rich π system can interact with a metal (cationic or neutral), an anion, another molecule and even another π system.[1]  Non-covalent interactions involving π systems are pivotal to biological events such as protein-ligand recognition.[2]

The most common types of π-interactions involve:

Metal-π Interactions: involves interaction of a metal and the face of a π system, the metal can be a cation (known as  cation-π interactions) or neutral

Polar-π interactions: involves interaction of a polar molecule and quadrupole moment a π system.

 

Metal-π interactions

Metal π interactions play a major role in organometallics. Linear and cyclic π systems bond to metals allowing organic complexes to bond to metals.


Ethylene  – π  In the most simple linear π systems, bonding to metals takes place through two interactions.  Electron density is donated directly to the metal like a  sigma bond would be formed. Also, the metal can donate electron density back to the linear π system (ethylene) from the metal’s d orbital to the empty π* orbital of ethylene.[8]

Electron density donated to the alkene π* orbital. Electron density donated to the metal like a Sigma bond


Cyclic systems

The specifics for binding of π cyclic systems are much more complex and depend on the electrons, the  HOMO, and the  LUMO  in each individual case of molecules. Cyclic π systems can bind monohapto or polyhapto depending on the individual situation. This means that  π bonds  can bind individually to the metal or there can be a single bond from the center of a  benzene  or  cyclopentadienyl complex. Of course the bonding modes (η1, η3, η5, etc.) determine the number of donated electrons (1, 3, 5, etc.). The diversity of these cyclic complexes allows for a seemingly endless number of metallic structures.[8]



Catalysis[edit]

The use of organometallic structures led by π – metal bonding plays an enormous role in the catalysis of  organic reactions. The  Stille reaction  is a widely known and important reaction in organic synthesis. π interactions with the Pd catalyst in this reaction are almost necessary in pushing this reaction to completion (alkyl groups transfer is rather slow).[9]  Other widely known reactions based on π – metal  catalysisinteractions are:

Heck reaction

Hiyama coupling

Kumada coupling

Negishi coupling

Petasis reaction

Sonogashira coupling

Suzuki reaction.

π metal interactions can also be involved directly with the function of  ligands  on the  catalyst. Chemistry involving  nickel  catalysis  of  Suzuki reactions  was greatly affected by  pyrazoles  and pyrazolates acting as coplanar ligand. The π interactions tied multiple  pyrazoles  and pyrazolates together around the  nickel  metal to cause reaction results.[10]

Another π metal interaction directly involved with catalysis involves  π stackingFerrocene  is the standard example where the metal (iron) is trapped in between two  cyclopentadienyl  ligands. These interactions are commonly referred to assandwich compounds.[8]



π-effects have an important contribution to biological systems since they provide a significant amount of binding enthalpy. Neurotransmitters produce most of their biological effect by binding to the active site of a protein receptor. Pioneering work of Dennis A. Dougherty is a proof that such kind of binding stabilization is the effect of cation-π interactions of the  acetylcholine  (Ach) neurotransmitter.[17][18]  The structure ofacetylcholine esterase  includes 14 highly conserved aromatic residues. The trimethyl ammonium group of Ach binds to the aromatic residue of  tryptophan  (Trp). The indole site provides a much more intense region of negative electrostatic potential than benzene and phenol residue of Phe and Tyr.  S-Adenosyl methionine  (SAM) can act as a catalyst for the transfer of methyl group from the sulfonium compound to nucleophile. The nucleophile can be any of a broad range structures including nucleic acids, proteins, sugars or C=C bond of lipids or steroids. The van der Waals contact between S-CH3  unit of SAM and the aromatic face of a Trp residue, in favorable alignment for catalysis assisted by cation-π interaction.

A great deal of circumstantial evidence places aromatic residues in the active site of a number of proteins that interact with cations but the presence of cation-π interaction in biological system does not rule out the conventional ion-pair interaction. In fact there is a good evidence for the existence of both type of interaction in model system.



The π system above and below the benzene ring leads to a  quadrupolecharge distribution.



Cation–π interaction between  benzene  and a sodium  cation.

Cation–π interaction  is a  noncovalent  molecular interaction  between the face of an electron-rich  π system  (e.g.  benzeneethyleneacetylene) and an adjacent  cation  (e.g. Li+, Na+). This interaction is an example of noncovalent bonding between a monopole (cation) and a  quadrupole  (π system). Bonding energies are significant, with solution-phase values falling within the same order of magnitude as  hydrogen bonds  and  salt bridges. Similar to these other non-covalent bonds, cation–π interactions play an important role in nature, particularly in  protein structuremolecular recognition  and  enzyme catalysis. The effect has also been observed and put to use in synthetic systems.[1][2]



Diagram of the HOMO and LUMO of a molecule. Each circle represents an electron in an orbital; when light of a high enough frequency is absorbed by an electron in the HOMO, it jumps to the LUMO.



Charge transport in disordered organic semiconductors[edit]

Charge transport in organic semiconductors is dependent on  π-bonding  orbitals and quantum mechanical wave-function overlap. In disordered organic semiconductors, there is limited π-bonding overlapping between molecules and conduction of charge carriers (electrons or holes) is described by  quantum mechanical tunnelling.[13]  Charge transport depends on the ability of the charge carriers to pass from one molecule to another. Because of the quantum mechanical tunnelling nature of the charge transport, and its subsequent dependence on a probability function, this transport process is commonly referred to as hopping transport.[14]  Hopping of charge carriers from molecule to molecule depends upon the energy gap between  HOMO  and  LUMO  levels. Carrier mobility is reliant upon the abundance of similar energy levels for the electrons or holes to move to and hence will experience regions of faster and slower hopping. This can be affected by both the temperature and the electric field across the system.

A theoretical study[15]  has shown that in a low electric field the conductivity of organic semiconductor is proportional to T−1/4  and in a high electric field is proportional to e−(E/aT), where  a  is a constant of the material. Another study shows that the  AC  conductivity of the organic semiconductor  pentacene  is frequency-dependent and provided evidence that this behavior is due to its  polycrystalline  structure and hopping conduction.[16]



Characterization[edit]

Organic semiconductors differ from inorganic counterparts in many ways. These include optical, electronic, chemical and structural properties. In order to design and model the organic semiconductors, such optical properties as absorption and photoluminescence need to be characterized.[9][10]  Optical characterization for this class of materials can be done using UV-visible absorption spectrophotometers and photoluminescence spectrometers. Semiconductor film appearance and morphology can be studied with  atomic force microscopy  (AFM) and  scanning electron microscopy  (SEM). Electronic properties such as ionisation potential can be characterized by probing the electronic band structure with  ultraviolet photoelectron spectroscopy  (UPS).[11]

The charge-carrier transport properties of organic semiconductors are examined by a number of techniques. For example, time-of-flight (TOF) and space charge limited current techniques are used to characterize “bulk” conduction properties of organic films. Organic field effect transistor (OFET) characterization technique is probing “interfacial” properties of semiconductor films and allows to study the charge carrier mobility, transistor threshold voltage and other FET parameters. OFETs development can directly lead to novel device applications such as organic-based flexible circuits, printable radio frequency identification tags (RFID) and active matrix backplanes for displays.[9][12]  Chemical composition and structure of organic semiconductors can be characterized by infrared spectroscopy,  secondary ion mass spectrometry  (SIMS) and  X-ray photoelectron spectroscopy  (XPS).

Nature of the cation-π interaction.

The most studied cation-π interactions involve binding between an  aromatic  π system and an  alkali metal  or  nitrogenous  cation. The optimal interaction geometry places the cation in van der Waals contact with the aromatic ring, centered on top of the π face along the 6-fold axis.[3]  Studies have shown that electrostatics dominate interactions in simple systems, and relative binding energies correlate well with  electrostatic potential energy.[4][5]

The Electrostatic Model developed by  Dougherty  and coworkers describes trends in binding energy based on differences in electrostatic attraction. It was found that interaction energies of cation-π pairs correlate well with electrostatic potential above the π face of arenes: for eleven Na+-aromatic adducts, the variation in binding energy between the different adducts could be completely rationalized by electrostatic differences. Practically, this allows trends to be predicted qualitatively based on visual representations of  electrostatic potential maps  for a series of arenes. It should be noted that electrostatic attraction is not the only component of cation-π bonding. For example, 1,3,5-trifluorobenzene interacts with cations despite having a negligible quadrupole moment. While non-electrostatic forces are present, these components remain similar over a wide variety of arenes, making the electrostatic model a useful tool in predicting relative binding energies. The other “effects” contributing to binding are not well understood.  Polarizationdonor-acceptor  and  charge-transfer  interactions have been implicated; however, energetic trends do not track well with the ability of arenes and cations to take advantage of these effects. For example, if induced dipole was a controlling effect,  aliphatic  compounds such as  cyclohexane  should be good cation-π partners (but are not).[4]

The cation–π interaction is noncovalent and is therefore fundamentally different than bonding between  transition metals  and π systems. Transition metals have the ability to share electron density with π-systems through  d-orbitals, creating bonds that are highly  covalent  in character and cannot be modeled as a cation-π interaction.

In atoms with a single electron (hydrogen-like atoms), the energy of an orbital (and, consequently, of any electrons in the orbital) is determined exclusively by  . The    orbital has the lowest possible energy in the atom. Each successively higher value of    has a higher level of energy, but the difference decreases as    increases. For high  , the level of energy becomes so high that the electron can easily escape from the atom. In single electron atoms, all levels with different    within a given    are (to a good approximation) degenerate, and have the same energy. This approximation is broken to a slight extent by the effect of the magnetic field of the nucleus, and by  quantum electrodynamicseffects. The latter induce tiny binding energy differences especially for  s  electrons that go nearer the nucleus, since these feel a very slightly different nuclear charge, even in one-electron atoms; see  Lamb shift.

In atoms with multiple electrons, the energy of an electron depends not only on the intrinsic properties of its orbital, but also on its interactions with the other electrons. These interactions depend on the detail of its spatial probability distribution, and so the  energy levels  of orbitals depend not only on    but also on  . Higher values of    are associated with higher values of energy; for instance, the 2p state is higher than the 2s state. When  , the increase in energy of the orbital becomes so large as to push the energy of orbital above the energy of the s-orbital in the next higher shell; when    the energy is pushed into the shell two steps higher. The filling of the 3d orbitals does not occur until the 4s orbitals have been filled.

The increase in energy for subshells of increasing angular momentum in larger atoms is due to electron–electron interaction effects, and it is specifically related to the ability of low angular momentum electrons to penetrate more effectively toward the nucleus, where they are subject to less screening from the charge of intervening electrons. Thus, in atoms of higher atomic number, the    of electrons becomes more and more of a determining factor in their energy, and the principal quantum numbers    of electrons becomes less and less important in their energy placement.

The energy sequence of the first 24  subshells (e.g., 1s, 2p, 3d, etc.) is given in the following table. Each cell represents a subshell with    and    given by its row and column indices, respectively. The number in the cell is the subshell's position in the sequence. For a linear listing of the subshells in terms of increasing energies in multielectron atoms, see the section below.

 

The “classic” neurotransmitters are stored in synaptic vesicles,  uniformly sized organelles, 40 – 50 nm in diameter. 

The length relates to the wavelength of soft X-rays from photo-fenton chemistry. The colloid within the neuron can act as a lens. Calcium influx important in signalling. Calcium can do electron capture so could be involved in photo-fenton type chemistry?

Nature Nanotechnology  5, 127 - 132 (2010) 
Published online: 20 December 2009 |  doi:10.1038/nnano.2009.452

Subject Categories:  Nanobiotechnology  |  Nanosensors and other devices  |Photonic structures and devices

Colloidal lenses allow high-temperature single-molecule imaging and improve fluorophore photostability

Jerrod J. Schwartz1,2, Stavros Stavrakis1,2  & Stephen R. Quake1

Abstract

Although single-molecule fluorescence spectroscopy was first demonstrated at near-absolute zero temperatures (1.8  K)1, the field has since advanced to include room-temperature observations2, largely owing to the use of objective lenses with high numerical aperture, brighter fluorophores and more sensitive detectors. This has opened the door for many chemical and biological systems to be studied at native temperatures at the single-molecule level both  in vitro3,  4  and  in vivo5,  6. However, it is difficult to study systems and phenomena at temperatures above 37  °C, because the index-matching fluids used with high-numerical-aperture objective lenses can conduct heat from the sample to the lens, and sustained exposure to high temperatures can cause the lens to fail. Here, we report that TiO2colloids with diameters of 2  µm and a high refractive index can act as lenses that are capable of single-molecule imaging at 70  °C when placed in immediate proximity to an emitting molecule. The optical system is completed by a low-numerical-aperture optic that can have a long working distance and an air interface, which allows the sample to be independently heated. Colloidal lenses were used for parallel imaging of surface-immobilized single fluorophores and for real-time single-molecule measurements of mesophilic and thermophilic enzymes at 70  °C. Fluorophores in close proximity to TiO2  also showed a 40%  increase in photostability due to a reduction of the excited-state lifetime.

 
calcium isotope stability.jpg
 
calcium isotope stability 2.jpg
 

Subconscious minds photo-Fenton biochemistry and atom isotopes role in the timing frequency (Hz) of subconscious mind biochemistry

Connect the dots and draw your own conclusions that are what I have done as well as develop my own smart drugs from food that provide a regenerative energy

IUBMB Life.  2007 Apr-May;59(4-5):280-5.

Calcium, iron and neuronal function.

Hidalgo C1,  Núñez MT.

Author information

Abstract

Calcium and iron play dual roles in neuronal function: they are both essential but when present in excess they cause neuronal damage and may even induce neuronal death. Calcium signals are required for synaptic plasticity, a neuronal process that entails gene expression and which is presumably the cellular counterpart of cognitive brain functions such as learning and memory. Neuronal activity generates cytoplasmic and nuclear calcium signals that in turn stimulate pathways that promote the transcription of genes known to participate in synaptic plasticity. In addition, evidence discussed in this article shows that iron deficiency causes learning and memory impairments that persist following iron repletion, indicating that iron is necessary for normal development of cognitive functions. Recent results from our group indicate that iron is required for long-term potentiation in hippocampal CA1 neurons and that iron stimulates ryanodine receptor-mediated calcium release through ROS produced via the Fenton reaction leading to stimulation of the ERK signaling pathway. These combined results support a coordinated action between iron and calcium in synaptic plasticity and raise the possibility that elevated iron levels may contribute to neuronal degeneration through excessive intracellular calcium increase caused by iron-induced oxidative stress.





Antioxid Redox Signal.  2007 Feb;9(2):245-55.

A role for reactive oxygen/nitrogen species and iron on neuronal synaptic plasticity.

Hidalgo C1,  Carrasco MAMuñoz PNúñez MT.

Author information

Abstract

A great body of experimental evidence collected over many years indicates that calcium has a central role in a variety of neuronal functions. In particular, calcium participates in synaptic plasticity, a neuronal process presumably correlated with cognitive brain functions such as learning and memory. In contrast, only recently, evidence has begun to emerge supporting a physiological role of reactive oxygen (ROS) and nitrogen (RNS) species in synaptic plasticity. This subject will be the central topic of this review. The authors also present recent results showing that, in hippocampal neurons, ROS/RNS, including ROS generated by iron through the Fenton reaction, stimulate ryanodine receptor-mediated calcium release, and how the resulting calcium signals activate the signaling cascades that lead to the transcription of genes known to participate in synaptic plasticity. They discuss the possible participation of ryanodine receptors jointly stimulated by calcium and ROS/RNS in the normal signaling cascades needed for synaptic plasticity, and how too much ROS production may contribute to neurodegeneration via excessive calcium release. In addition, the dual role of iron as a necessary, but potentially toxic, element for normal neuronal function is discussed.



Ageing Res Rev.  2004 Nov;3(4):431-43.

Reactive oxygen species and synaptic plasticity in the aging hippocampus.

Serrano F1,  Klann E.

Author information

Abstract

Aging is associated with a general decline in physiological functions including cognitive functions. Given that the hippocampus is known to be critical for certain forms of learning and memory, it is not surprising that a number of neuronal processes in this brain area appear to be particularly vulnerable to the aging process. Long-term potentiation (LTP), a form of synaptic plasticity that has been proposed as a biological substrate for learning and memory, has been used to examine age-related changes in hippocampal synaptic plasticity. A current hypothesis states that oxidative stress contributes to age-related impairment in learning and memory. This is supported by a correlation between age, memory impairment, and the accumulation of oxidative damage to cellular macromolecules. However, it also has been demonstrated that ROS are necessary components of signal transduction cascades during normal physiological processes. This review discusses the evidence supporting the dual role of reactive oxygen species (ROS) as cellular messenger molecules in normal LTP, as well their role as damaging toxic molecules in the age-related impairment of LTP. In addition, we will discuss parallel analyses of LTP and behavioral tests in mice that overexpress antioxidant enzymes and how the role of antioxidant enzymes and ROS in modulating these processes may vary over the lifespan of an animal.



IUBMB Life.  2005 Apr-May;57(4-5):315-22.

The ryanodine receptors Ca2+ release channels: cellular redox sensors?

Hidalgo C1,  Donoso PCarrasco MA.

Author information

Abstract

The release of Ca2+ from intracellular stores mediated by ryanodine receptors (RyR) Ca2+ release channels is essential for striated muscle contraction and contributes to diverse neuronal functions including synaptic plasticity. Through Ca2+-induced Ca2+-release, RyR can amplify and propagate Ca2+ signals initially generated by Ca2+ entry into cardiac muscle cells or neurons. In contrast, RyR activation in skeletal muscle is under membrane potential control and does not require Ca2+ entry. Non-physiological or endogenous redox molecules can change RyR function via modification of a few RyR cysteine residues. This critical review will address the functional effects of RyR redox modification on Ca2+ release in skeletal muscle and cardiac muscle as well as in the activation of signaling cascades and transcriptional regulators required for synaptic plasticity in neurons. Specifically, the effects of endogenous redox-active agents, which induce S-nitrosylation or S-glutathionylation of particular channel cysteine residues, on the properties of muscle RyRs will be discussed. The effects of endogenous redox RyR modifications on cardiac preconditioning will be analyzed as well. In the hippocampus, sequential activation of ERKs and CREB is a requisite for Ca2+-dependent gene expression associated with long lasting synaptic plasticity. Results showing that reactive oxygen/nitrogen species modify RyR channels from neurons and the RyR-mediated sequential activation of neuronal ERKs and CREB produced by hydrogen peroxide and other stimuli will be also discussed.



IUBMB Life.  2007 Apr-May;59(4-5):280-5.

Calcium, iron and neuronal function.

Hidalgo C1,  Núñez MT.

Author information

Abstract

Calcium and iron play dual roles in neuronal function: they are both essential but when present in excess they cause neuronal damage and may even induce neuronal death. Calcium signals are required for synaptic plasticity, a neuronal process that entails gene expression and which is presumably the cellular counterpart of cognitive brain functions such as learning and memory. Neuronal activity generates cytoplasmic and nuclear calcium signals that in turn stimulate pathways that promote the transcription of genes known to participate in synaptic plasticity. In addition, evidence discussed in this article shows that iron deficiency causes learning and memory impairments that persist following iron repletion, indicating that iron is necessary for normal development of cognitive functions. Recent results from our group indicate that iron is required for long-term potentiation in hippocampal CA1 neurons and that iron stimulates ryanodine receptor-mediated calcium release through ROS produced via the Fenton reaction leading to stimulation of the ERK signaling pathway. These combined results support a coordinated action between iron and calcium in synaptic plasticity and raise the possibility that elevated iron levels may contribute to neuronal degeneration through excessive intracellular calcium increase caused by iron-induced oxidative stress.



Antioxid Redox Signal.  2007 Feb;9(2):245-55.

A role for reactive oxygen/nitrogen species and iron on neuronal synaptic plasticity.

Hidalgo C1,  Carrasco MAMuñoz PNúñez MT.

Author information

Abstract

A great body of experimental evidence collected over many years indicates that calcium has a central role in a variety of neuronal functions. In particular, calcium participates in synaptic plasticity, a neuronal process presumably correlated with cognitive brain functions such as learning and memory. In contrast, only recently, evidence has begun to emerge supporting a physiological role of reactive oxygen (ROS) and nitrogen (RNS) species in synaptic plasticity. This subject will be the central topic of this review. The authors also present recent results showing that, in hippocampal neurons, ROS/RNS, including ROS generated by iron through the Fenton reaction, stimulate ryanodine receptor-mediated calcium release, and how the resulting calcium signals activate the signaling cascades that lead to the transcription of genes known to participate in synaptic plasticity. They discuss the possible participation of ryanodine receptors jointly stimulated by calcium and ROS/RNS in the normal signaling cascades needed for synaptic plasticity, and how too much ROS production may contribute to neurodegeneration via excessive calcium release. In addition, the dual role of iron as a necessary, but potentially toxic, element for normal neuronal function is discussed.



Toxicol Lett.  2015 Apr 16. pii: S0378-4274(15)00137-X. doi: 10.1016/j.toxlet.2015.04.008. [Epub ahead of print]

Endogenous  hydrogen peroxide  in the hypothalamic paraventricular nucleus regulates neurohormonal excitation in high salt-induced hypertension.

Zhang M1,  Qin DN2,  Suo YP3,  Su Q1,  Li HB1,  Miao YW1,  Guo J1,  Feng ZP1,  Qi J1,  Gao HL1,  Mu JJ4,  Zhu GQ5,  Kang YM6.

Author information

Abstract

Reactive oxygen species (ROS) in the  brain  plays an important role in the progression of hypertension and  hydrogen peroxide  (H2O2) is a major component of ROS. The aim of this study is to explore whether endogenous H2O2  changed by polyethylene glycol-catalase (PEG-CAT) and aminotriazole (ATZ) in the hypothalamic paraventricular nucleus (PVN) regulates neurotransmitters, renin-angiotensin system (RAS), and cytokines, and whether subsequently affects the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in high salt-induced hypertension. Male Sprague-Dawley rats received a high-salt diet (HS, 8% NaCl) or a normal-salt diet (NS, 0.3% NaCl) for 10 weeks. Then rats were treated with bilateral PVN microinjection of PEG-CAT (0.2 i.u./50nl), an analog of endogenous catalase, the catalase inhibitor ATZ (10nmol/50nl) or vehicle. High salt-fed rats had significantly increased MAP, RSNA, plasma norepinephrine (NE) and pro-inflammatory cytokines (PICs). In addition, rats with high-salt diet had higher levels of NOX-2, NOX-4 (subunits of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), interleukin-1beta (IL-1β), glutamate and NE, and lower levels of gamma-aminobutyric acid (GABA) and interleukin-10 (IL-10) in the PVN than normal diet rats. Bilateral PVN microinjection of PEG-CAT attenuated the levels of RAS and restored the balance of neurotransmitters and cytokines, while microinjection of ATZ into the PVN augmented those changes occurring in hypertensive rats. Our findings demonstrate that ROS component H2O2  in the PVN regulating MAP and RSNA are partly due to modulate neurotransmitters, renin-angiotensin system, and cytokines within the PVN in salt-induced hypertension.



Exp Physiol.  2011 Dec;96(12):1282-92. doi: 10.1113/expphysiol.2011.059733. Epub 2011 Sep 2.

Endogenous  hydrogen peroxide  in paraventricular nucleus mediates sympathetic activation and enhanced cardiac sympathetic afferent reflex in renovascular hypertensive rats.

Xu Y1,  Gao QGan XBChen LZhang LZhu GQGao XY.

Author information

Abstract

An enhancement of the cardiac sympathetic afferent reflex (CSAR) contributes to sympathetic activation in renovascular hypertension. Angiotensin II in the paraventricular nucleus (PVN) augments the CSAR and increases sympathetic outflow and blood pressure. The present study aimed to determine whether endogenous  hydrogen peroxide  in the PVN mediated the enhanced CSAR, sympathetic activity and the effects of angiotensin II in the PVN in renovascular hypertension induced by the two-kidney, one-clip method (2K1C) in rats. At the end of the fourth week, the rats underwent sino-aortic and vagal denervation under general anaesthesia with urethane and α-chloralose. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. The CSAR was evaluated by the RSNA response to epicardial application of bradykinin. Microinjection of polyethylene glycol-catalase (PEG-CAT), an analogue of endogenous catalase, into the PVN decreased the RSNA and MAP and abolished the CSAR in both sham-operated and 2K1C rats. Microinjection into the PVN of the catalase inhibitor, aminotriazole, increased the RSNA and MAP and enhanced the CSAR. The effects of PEG-CAT or aminotriazole were greater in 2K1C rats than in sham-operated animals. The effects of angiotensin II in the PVN were abolished by pretreatment with PEG-CAT in both sham-operated and 2K1C rats; however, aminotriazole failed to potentiate the effects of angiotensin II. The catalase activity was decreased but the H(2)O(2) levels were increased in the PVN of 2K1C rats. These results indicate that endogenous H(2)O(2) in the PVN not only mediates the enhanced sympathetic activity and CSAR, but also the effects of angiotensin II in the PVN in renovascular hypertensive rats.