Nitric oxide and cognitive function -
Also, nNOS takes place in acoustic overstimulation condition. Inner hair cells release excess glutamate during continuous stimulation. This glutamate increase calcium influx to afferent dendrites where nNOS produce NO.
Then overproduction of NO due to acoustic overstimulation kills afferent dendrites because of excitotoxicity [ 43 ]. Auditory nerve, lateral wall, vestibule and cochlear neuroepithelium are the areas where NOS activity is the highest in the auditory system.
nNOS is the predominant isoform in the cochlea [ 44 ]. In a gerbil study, researchers examined the role of NO in cochlelar excitotoxicity. Cochlear compound action potentials thresholds were recorded with NOS inhibitor and glutamate exposed conditions. Overstimulation with glutamate caused NO-mediated excitotoxicity in the cochlea.
NOS inhibition should be neuroprotective for cochlea [ 45 ]. To trigger iNOS expression in cochlea, bacterial lipopolysaccharides and tumour necrosis factor α was injected to guinea pigs.
The iNOS expression was higher than eNOS and nNOS during that experiment. This dispersed iNOS is caused by the bacterial lipopolysaccharide-triggered immune response. In another study with immonostaining data, the distribution of NOSs was determined in the auditory system. nNOS was dispersed in the inner and outer hair cells, spiral ganglion cells, cells of the stria vascularis, spiral ligament cells and vessel cells near the modiolus.
eNOS was dispersed in vascular endothelial cells, and in spiral ganglion cells. If there were not immune stimulus there would be no iNOS in cochlea [ 47 ].
NOS enzymes have important duties during pathophysiology of unhealthy brains. Under that heading various diseases, pathologies, malfunctions and disabilities of brains will be evaluated from the point of view of NOSs.
It is very hard to diagnose the neuropsychiatric diseases properly; however, there are globally accepted parameters. Although the criteria for diagnosis is generally evaluated at certain times by prestigious committees and there is still hardships for diagnosis. One of the main goals of the scientists working on neuropsychiatric disorders is to pair a marker molecule with a disease to facilitate the diagnosis.
So far there is not any coupling for any NOSs for any neuropsychiatric disorder as a marker but NOSs have various roles for these diseases. NOS has roles for these abnormalities. In patients with depression it was shown that NO expression altered via eNOS.
Besides NO modulates neuropeptides, such as vasopressin, oxytocin and corticotrophin-releasing factor. According to post-mortem studies on depression patients, NO signalling was impaired in their hypothalami [ 48 ]. Major depression disorder MDD will be one of the dominant causes of disability by the year Also NO levels and NOS expressions are higher in MDD patients.
Besides, with mice studies, it was shown that there is a correlation between NOS mechanism and depression. NOS inhibitors could be researched as a new target for antidepressant strategies [ 4 , 22 ]. In a population study done in Taiwan with MDD patients in which the potential genetic variations with healthy and MDD subjects according to their nNOS polymorphisms was researched.
There is no difference between subjects; the frequencies are similar for controls and MDD patients [ 49 ]. In an autopsy and tissue bank-based study from Holland, there is decrease in nNOS expression in the anterior cingulate cortex of MDD-diagnosed people [ 50 ].
In mice along with stress-induced depression, nNOS expression increases in the hippocampi. Due to excitotoxicity neurogenesis in hippocampi is suppressed. To inhibit nNOS signalling may be a novel approach for depression treatment [ 51 ]. Also, iNOS is involved in stress-triggered depression. NO derived from iNOS and mRNA levels of iNOS increased in cortices of depression model applied mice [ 52 ].
Also in a population study there is no correlation between genetic polymorphisms and MDD. In Japanese population MDD patients were investigated for polymorphisms in their nNOS genes, but found no variation between controls and MDD [ 53 ].
From a Czech Republic population genetic study, there is also no correlation between eNOS and MDD [ 54 ]. A population study from United Kingdom found a correlation between single nucleotide polymorphisms in nNOS gene and psychosocial stress-triggered depression.
The individuals carrying those polymorphisms have a tendency to develop depression if they face financial hardship [ 55 ]. There is a link between vascular problems, depressive behaviours and NO metabolism. When vascular dysfunction emerges after depressive symptoms, the characteristics behind it show lack of bioavailable NO.
However, H 2 O 2 covers up that deficit [ 56 ]. There are studies on ethnopharmacological level to find out if there is a potential drug candidate in botanical material. To investigate NO metabolism is one of the target pathways to detect for antidepressant-like and neuroprotective potential.
Aloysia grattissima has the potential to treat depressive disorders depending on the NO metabolism manipulating properties of its extracts [ 57 ].
Thus, nNOS depending on population genetics studies combined with behaviour is a potential research area [ 58 ]. For anxiety-like and depression-like behaviours, there is a strong evidential pathway, hypothalamic-pituitary-adrenal axis HPA.
Also on the ecotoxicological aspect, the nutrients for newborns and expectant mothers are very important because they fall in the risk group. nNOS knockout mice show abnormal social behaviour, hyperactivity and impaired remote spatial memory [ 60 ].
It is important to demonstrate how nitric oxide synthases are affected in the brain by psychotropic drugs. Orally treated rats with several psychotropics were sacrificed and iNOS gene expressions in the brain were detected. Psychotropics including antidepressants and anxiolytics modulate the gene expression of iNOS in rat brain [ 61 ].
It is a complex and controversial psychological situation: suicide. This behaviour has a strong genetic background. In a study it was shown that a single nucleotide polymorphism of nNOS gene has a correlation between suicides in Japanese population, especially in males [ 62 ].
Schizophrenia is a complex illness including biochemical, anatomical and genetic aspects of its pathology. Alois Alzheimer defined the illness during the early s.
Deficits in short-term memory formation are characteristic for AD. NOSs are very important for creating the new trails between neurons. NOSs take place for activating the presynaptic neurons receptors. However, in the pathology of the AD the harmonization created by NOSs between neurons is blocked by plaques [ 20 — 22 , 64 ].
In the brain of an AD patient, β-amyloid peptide aggregates in senile plaques and the arginine within the astrocytes accumulates. These are the classical neuropathology of the disease. Arginine-metabolizing enzymes like NOSs and their association with amyloid peptides are important.
The correlation of Aβ-peptide fragments with nNOS has been searched with spectrofluorimetry. The interaction of Aβ-peptide with nNOS causes the molecular movement of two critical tryptophan residues in the structure of the enzyme [ 65 ]. Purified nNOS was incubated with Aβ-peptide fragments during 96 hours.
The kinetics of the interaction was introduced; nNOS was the amyloidogenic catalyst and all Aβ-peptide fragments were inhibited nNOS [ 66 ]. Data from cell culture studies, knockout mice studies and behavioural studies showed that eNOS has a crucial role for decelerating the pathology of AD [ 67 ].
James Parkinson described the disease during the s. The disease is diagnosed generally between 50 and 70 years old people.
The mechanism behind PD is still unknown. But the dopamine metabolism decreases significantly in PD; also substantia nigra is one of the potential areas of interest to study the disease. PD is an illness affecting the dopaminergic pathway in the brain. NO inflict the injuries in dopaminergic neurons.
There are several evidences from NOS inhibitor studies about this correlation. However, if a cell goes for the cell death pathway, NO accelerates the process [ 69 ]. Nitration of α-synuclein triggers the protein aggregation, which worsens the pathology.
This mechanism is used to mimic the PD in cell culture [ 70 ]. Scientists are trying to create a thorough model of the disease for in vivo or in vitro , however, so far there is not a completely satisfying model. That is caused by the unknown mechanism behind the illness. To mimic PD a group of researchers castrated the male mice.
According to the iNOS results, the castration of young male mice induces PD pathologies [ 71 ]. Nutrition and false diet should be a cause of the disease. As a strategy to add an antioxidant-rich nutritive to the diet may be beneficial. Rats were supplied with pomegranate juice after a PD model.
The change in the diet by adding pomegranate juice enhanced the iNOS expression in the animal brain [ 72 ]. There are lots of cancer types present in the head and neck area.
But in this section, only cancers originating from cells inside the cranium will be discussed and not the metastatic pathologies. There are lots of studies done with cultured cancer cells from various mammals; however, studies done with tumour samples from human are rare.
Instead of discussing the cell culture studies, it was important to gather the knowledge, which was hard to reach. Most of cancer cell culture studies are done without the healthy control cell lines or experimental models.
But some cancer cell culture studies will be discussed. A biopsy study done with gliomas, and also with meningiomas, showed that all three NOS isoforms were present in the aforementioned tumours.
nNOS was significantly dominant in glial cells of gliomas. However, that NOS dense status becomes sparse in the peritumoral tissues [ 73 ]. NOSs of tumour cells, opposite to the healthy cells, synthesize predominantly superoxide and peroxynitrite, which generate oxidative stress [ 74 ]. Neuroblastoma cell lines are generally used due to their ability to differentiate neuron-like cells.
NOS inhibition in Neuro2a cells blocked that differentiation; it is possible to speculate that nNOS may have important roles for dissolving a neuroblastoma tumour [ 75 ].
These types of cancers are dominant and dangerous when compared to other brain cancers. Similar results were reported also from a similar study. iNOS expression was increased in grade I, II and III astrocytic gliomas. However, in the same study it was shown that the iNOS expression was decreased for grade IV astrocytic gliomas [ 77 ].
In a study with primary astrocytoma biopsy samples prove that eNOS and VEGF work cooperatively in tumour angiogenesis [ 78 ]. Besides, in another study, it was shown that astrocytic tumour vessels have more eNOS expression than normal vessels [ 79 ]. Also, it is known that nNOS expression increases in glioma tumours.
In a study done on rats searched for the immune responses of oily cyst content of human craniopharyngioma. Immunohistochemical studies after injection revealed that eNOS expression increased in a time course manner [ 80 ].
Medulloblastomas are highly malignant brain tumours generally affecting children and adolescents. In a study done with medulloblastoma cells revealed that NOS has important roles in medulloblastoma cell death.
Scientists applied various chemotherapy agents and PDE5 inhibitors to kill cells. Then, they co-treated cells with L-NAME and found out that NOS inhibition accompanying PDE5 inhibitors suppressed cell killing.
A study done in knockout mice exhibited that iNOS has an important role in medulloblastoma formation. Ptch1 heterozygous and iNOS-deficient mice developed medulloblastoma two times higher than Ptch1 heterozygous and iNOS producing mice.
According to studies done with human ptiutary tumour biopsy samples, scientists tried to reveal the roles of NOSs with the disease. In human pituitary adenomas, eNOS expression increased, whereas iNOS and nNOS were stabile [ 83 ]. Another human biopsy study showed that highly invasive adenomas have higher upregulated iNOS, whereas noninvasive adenomas did not have upregulated iNOS.
Also, eNOS had upregulation with haemorrhagic adenomas [ 84 ]. Schwannomas are benign tumours originating from the Schwann cells. It can arise in any peripheral nerve; however, the frequent version arose around the acoustic nerve.
Immunohistochemical study done on human biopsy samples revealed that iNOS has a strong expression for this illness. In conclusion, it is possible to suggest that both clinical and experimental studies are important on the aspect of NOS and brain cancers.
It is very hard to mimic pathologies of some brain cancers both in animals and in vitro. Likewise, collecting clinical samples from patients is very hard. Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3. Edited by Seyed Soheil Saeedi Saravi.
Open access peer-reviewed chapter Role of Nitric Oxide Synthase in Normal Brain Function and Pathophysiology of Neural Diseases Written By Melih Dagdeviren.
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IntechOpen Nitric Oxide Synthase Simple Enzyme-Complex Roles Edited by Seyed Soheil Saeedi Saravi. From the Edited Volume Nitric Oxide Synthase - Simple Enzyme-Complex Roles Edited by Seyed Soheil Saeedi Saravi Book Details Order Print.
Chapter metrics overview 1, Chapter Downloads View Full Metrics. Impact of this chapter. Abstract Nitric oxide synthase has three isoforms; according to their roles and tissues or cells they are involved.
Keywords NOS learning depression brain cancers. dagdeviren ege. Introduction Nitric oxide NO also known as nitrogen oxide or nitrogen monoxide is a small molecule, which is a gaseous secondary messenger in mammalian cells [ 1 ].
Roles of NOSs in learning and memory formation One of the main duties of NOS enzymes in the healthy brain is learning and memory formation.
Roles of NOSs in seeing and retinal function Retinal function is very important for developed organisms, and retinal function has various molecular pathways.
Roles of NOSs in hearing and cochlea Hearing starts at the outer ear and stimuli travels through tympanum and bones and finally arrives at the cochlea, where hair cells and nerve fibres take action.
Roles of NOSs in neuropsychiatric diseases It is very hard to diagnose the neuropsychiatric diseases properly; however, there are globally accepted parameters.
Roles of NOSs in neurodegenerative diseases Alois Alzheimer defined the illness during the early s.
Roles of NOSs in brain cancers There are lots of cancer types present in the head and neck area. References 1. Maines MD. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Paharmacol Toxicol. DOI: Zetterstrom R.
The Nobel Prize-discovery of the role of nitric oxide as a signalling molecule. Acta Paediatr. Fedele E, Raiteri M.
Dagdeviren M, Dogan YH, Kanit L. Effects of restraint stress and nitric oxide synthase inhibition on learning and strategy preference in young adult male rats. Balkan Med J. Forstermann U, Sessa WC. Nitric oxide synthases: regulation and function.
Eur Heart J. Andrew PJ, Mayer B. Enzymatic function of nitric oxide synthases. Cardiovasc Res. Heiss C, Rodriguez-Mateos A, Kelm M. Central Role of eNOS in the maintenance of endothelial homeostasis.
Antioxid Redox Signal. Steinert JR, Chernova T, Forsythe ID. Tau promotes the export of neuronal iron by facilitating the trafficking of APP to the plasma membrane. The study suggested that Alzheimer disease, Parkinson disease and tauopathies that are associated with the iron toxicity due to the loss of soluble tau could in principle be rescued by a pharmacological agent such as clioquinol, an iron chelator Lei et al.
Several studies reported that iron deposition was increased in the substantia nigra according to the severity of the disease in PD patients SN Dexter et al.
The researchers used plasma spectroscopy to detect iron concentration quantitatively in various brain regions Dexter et al.
In PD brain, histology studies showed that iron accumulate in neurons and glia in SN Jellinger et al. Furthermore, there are reports that a dysfunction in the IRP-IRE system that results in iron accumulation gave rise to α-Syn-induced toxicity Li et al.
Similarly, in almost all PD patient brains the Lewy bodies contained aggregated α-Syn Wakabayashi et al. The reason for iron accumulation in SN is unclear. Several hypotheses proposed include increased brain-blood-barrier BBB permeability Faucheux et al. Cellular iron accumulation in PD brain may be caused by elevated influx or decreased efflux.
Inflammation could contribute to iron accumulation by either increasing DMT1 uptake activity or TfR transport activity. In a mouse model, DMT1 activity was increased to mediate the iron uptake Salazar et al. NO is a gaseous signaling molecule that initially was thought as a dilator in blood vessels, with guanylyl cyclase as the major effector.
NO binds to the heme group of guanylyl cyclase and activates it in the presence of iron. High cGMP level are associated with release of neurotransmitters including glutamate, acetylcholine and glycine.
NO participates in tumor and bacteria immunity and in the central nervous system, it acts as a retrograde neurotransmitter. In the nervous system, NO has both physiological and pathological functions.
For example, NO contributes to long-term potentiation LTP and long-term depression LTD , and thus it plays a role in learning and memory Schuman and Madison, ; Shibuki and Okada, ; Lev-Ram et al. NO enhances CREB expression to mediate the response to brain-derived neurotrophic factor Riccio et al.
The synaptic NMDARs mediate neuroprotection, while the extrasynaptic NMDARs mediate neurodegeneration Talantova et al. NO also binds to other iron-containing proteins, such as mitochondrial aconitase. The interaction between mitochondrial aconitase and superoxidase are the major cause to mitochondrial damage Vasquez-Vivar et al.
Most of the cytotoxicity of NO is attributed to the production of peroxynitrite Pacher et al. Peroxynitrite is produced from the diffusion-controlled reaction between NO and superoxide in vivo Squadrito and Pryor, Peroxynitrite is a strong oxidant and it interacts with electron-rich groups, including Fe—S cluster.
Peroxynitrite is an important intermediator for protein nitration and oxidation, lipid peroxidation, mitochondria dysfunction, and finally causes apoptosis and necrosis Radi, NO is produced by NOS through the conversion of L-arginine to citrulline.
Three distinct NOS isoforms have been identified in the brain Forstermann et al. Neuronal NOS nNOS is expressed in neurons, while endothelial eNOS is expressed in brain endothelial cells. Inducible NOS iNOS is expressed in glia cells upon brain injury or inflammation. Inducible NOS produces a large amount of NO upon stimulation by proinflammatory cytokines over a long period of time Green et al.
In human immune response, NO is produced by phagocytes such as monocytes, macrophages, and neutrophils. In phagocytes, interferon-gamma IFN-γ or tumor necrosis factor TNF activates iNOS Green et al. On the other hand, transforming growth factor-beta TGF-β , interleukin-4 IL-4 or IL weakly inhibits iNOS.
As such, phagocytes contribute to inflammatory and immune responses via NO Green et al. In an immune response, NO is secreted as free radicals that is toxic to intracellular pathogens.
The modes of action are via DNA damage Wink et al. The molecular effects of NO depend on two kinds of reactions: S-nitrosylation of thiols and the nitrosylation of some metalloenzymes. Guanylate cyclase, a NO activated heme-containing enzyme, is an essential component of the relaxing function of NO on smooth muscles Derbyshire and Marletta, In addition to neuro-inflammatory stimuli, induction of iNOS expression in astrocytes, macrophages, and microglia by Aβ oligomers or by toxins such as 1-methylphenyl-1,2,3,6-tetrahydropyridine MPTP have been reported to increase NO levels in the degenerating brain Liberatore et al.
However, in the Tg APP AD mouse model, ablation of iNOS exacerbated spatial learning and memory and tau pathology, providing evidence that NO may have a neuroprotective role Wilcock et al.
NO targeted proteins have been partially characterized. NO can interact with Fe—S cluster containing protein and influence their enzyme activity. Cytosolic iron concentrations sensed by IRPs could post-transcriptionally adjust the expression of iron metabolizing genes to optimize the availability of labile iron.
IRPs bind to iron-responsive elements IRE , which are specific non-coding mRNA sequences, to control iron metabolism. IREs are of 30 nucleotide in length found along RNA motifs, and they contain the CAGUGN sequence the classic IRE motif that form a stem-loop structure Molokanova et al.
IRP1 and IRP2 are examples of two RNA-binding proteins that interact with IRE to modulate the translation of either the ferritin or Fpn mRNA, and they also control the stability of TfR and DMT1 mRNAs.
The binding of IRPs and IREs is regulated by free iron concentration. Therefore, IRPs can act as either a translation enhancer or inhibitor Pantopoulos, ; Piccinelli and Samuelsson, The decreased expression of ferritin and Fpn reduces free iron binding and export, leading to an increased in availability of labile iron for use by the cell.
Examples of transcripts that contain IREs include those that encode the ferritin subunits L and H, TfR, Fpn, DMT1, mitochondrial aconitase, succinate dehydrogenase, erythroid aminolevulinic acid synthetase, amyloid precursor protein and a-synuclein.
These downstream genes suggest that iron has close regulation of iron metabolism, redox and neurodegeneration via the IRP-IRE system. NO could regulate IRP-IRE binding, which in turn regulates many iron metabolism-related proteins Figure 2. Similarly, NO can regulate ferritin, Fpn and TfR via regulating the interaction of IRP-IRE binding, and hence regulate iron metabolism Figure 3.
Another report also showed that NO can enhance iron deposition in the brain via decreasing APP expression Ayton et al. The authors reported obvious decrease in expression of APP in substantia nigra of PD brain. APP KO mice have iron-dependent dopaminergic neuron loss, while APP overexpressing mice have protection effect in MPTP mouse model, as APP facilitates iron efflux.
NO decreases APP expression via the IRP-IRE system and this may explain how NO leads to dopaminergic neuron loss in PD. Figure 2. Schematic chart showing how NO regulate iron homeostasis. NO regulates IRP-IRE binding through redox reaction with Fe—S cluster in IRP, hence regulates the transcription of iron-metabolism-related proteins, and elevates intracellular iron level.
NO also directly S-nitrosylates DMT1, which enhances DMT1 transporter function. In addition, NO S-nitrosylates Dexras 1 and enhances the binding of Das1-PAP7-DMT1 complex and finally enhances iron uptake.
Figure 3. The regulation of NO on iron homeostasis in the brain during neuroinflammation. Large amount of NO was produced by microglia and astrocytes upon activation of iNOS during neuroinflammation.
NO enhanced the translation of TfR and DMT1 and decreased the translation of Fpn, hence increased iron accumulation in neurons.
The iron accumulation leads to oxidative stress and finally caused neurodegeneration. NO also regulates iron metabolism-related proteins in other ways, such as S-nitrosylation Figure 2.
Recently, we have shown that NO directly modulated DMT1 and enhanced its function via S-nitrosylation. This is unexpected as S-nitrosylation of proteins important in PD such as Parkin and XIAP resulted in compromised functions. Besides, many S-nitrosylated proteins have been identified in the past decade, and of note, those that have been functionally characterized have a loss-of-function Nakamura et al.
The potential therapeutic use of iron chelators gained much attention in recent years Ward et al. The strategy to target iron deposition is either to chelate iron directly or to regulate iron homeostasis, including NO-regulated iron absorption.
The candidate compounds should be BBB-permeant and easily penetrate cell membrane, chelate free iron and minimize the side effect to normal iron metabolism. Several iron chelators were used to deplete excessive iron and yielded promising clinical outcome.
The syndrome was improved and the iron content in SN significantly decreased as monitored by MRI Devos et al. Deferiprone seems quite promising so far, and is waiting to be tested in further clinical trial in larger population.
Furthermore, in several in vivo PD models, iron chelators, including deferasirox, deferrioxamine, VAR and D, have been used to significantly attenuate DA neuronal loss Ghosh et al.
Desferrioxamine has been shown to decelerate AD progression Rogers and Lahiri, However, as DFO is unstable with poor BBB permeability Bandyopadhyay et al. As clioquinol has side effects associated with myelopathies Zhang et al.
However, in another Phase II trial announced by the Australian company Prana Biotechnoloy in , PTB2 failed to improve brain amyloid deposition, neuronal function, brain atrophy and cognition in a one-year course treatment.
Besides direct chelation of iron, potent nontoxic IRE inhibitors with excellent BBB penetrating capacity were also thought to have high therapeutic significance in neurodegenerative diseases.
The IRE inhibitors that down-regulate translation of APP and α-Syn and prevent protein aggregation can support survival of neurons. To date, a few promising drug candidates of IRE inhibitors have been characterized and are being tested in various clinical trials for AD and PD patients Zhou and Tan, Posiphen is a natural product that has been shown to inhibit translation of both APP and a-synuclein proteins.
Furthermore, it is nontoxic and potent Rogers et al. The inhibitory effect has been validated by various experiments done in vitro and in vivo Lahiri et al.
The compound is still waiting for further clinical trials to test the efficacy for AD and PD Bandyopadhyay et al. Another compound JTR, screened from a ,compound library, was identified to have a more potent effect on APP translation than posiphen. Another case for targeting iron homeostasis is inhibiting DMT1 function.
To inhibit NO-mediated DMT1 functional increase, we used the NOS inhibitor L-name to reduce NO-mediated iron deposition in LPS-evoked mouse inflammatory model. L-NAME significantly ameliorated SN dopaminergic neuron loss and LPS-induced behavior deficit Liu et al.
Iron homeostasis is elaborately regulated in the human brain, and iron accumulation is closely associated with neurodegenerative diseases. NO regulates iron deposition at several levels. So far, therapeutic targeting of iron deposition has yielded some promising results, and further clinical trials in larger populations are still needed.
There are still some questions that remained unresolved. For example, how iron is transported through brain capillary epithelial cells and more specifically, how S-nitrosylation of DMT1 enhanced its transporter activity. A real-time, quantitative and in vivo detection technique will be extremely valuable for the field.
CL and MCL drafted the manuscript. TWS critically edited the manuscript. All authors approved the final version of the manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Aisen, P. Chemistry and biology of eukaryotic iron metabolism. Cell Biol. doi: CrossRef Full Text Google Scholar.
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Castellani, R. Acta Neuropathol. Cheah, J. III, Papadopoulos, V. NMDA receptor-nitric oxide transmission mediates neuronal iron homeostasis via the GTPase Dexras1.
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Schmidt, F. Hofmann, and J. Stasch Berlin: Springer , 17— Devos, D. Redox Signal. Dexter, D. Neural Transm. Increased nigral iron content in postmortem Parkinsonian brain.
Lancet 2, — Supporting NO also improves vascular function and endothelial function, which may also provide protective benefits against the effects of COVID since the SARS-CoV-2 virus attacks endothelial function and this becomes a major cause of mortality.
Overall, NO has a vital and positive effect on general health, mental health, the aging process, and even helps to repair skin damage. A lack of adequate NO production increases the risk of depression and the presence of NO positively affects our mood.
Depression is linked to increased expression of two enzymes that make nitric oxide; neuronal nitric oxide synthase and inducible nitric oxide synthase. A variant of the gene that makes these synthases increases depression susceptibility Aprehart-Treichel, Decreased NO production reduces blood flow to the brain and increases inflammation and oxidative stress which contributes to cognitive decline.
Nitric Oxide helps reduce anxiety and depression in part because it reduces inflammation and oxidative stress. It also restores circulation and supports healthy blood pressure, which is often elevated in people under stress and with chronic PTSD , thus becoming another risk factor for vascular dementia.
Nitric oxide function diminishes as we age and leads to what is called functional aging. Among the causes of diminished nitric oxide production are the SAD diet , Standard American Diet made up of refined flours and sugars and hydrogenated fats, sedentism, stress, medications like antibiotics, antidepressants , birth control pills, NSAIDs, PPIs, and exposure to pollution, toxins, and heavy metals.
By improving these lifestyle factors along with supplementation and foods that enrich nitric oxide, we can reverse and slow depletion. In my clinical practice and teaching institute , I focus on treating mental health, cognitive performance, help people taper psychotropic medications, and prevent diabetes and dementia.
Want to learn more? Aprehart-Treichel, J. Nitric Oxide Gene Variant May Affect Depression Risk. Psychiatric News. Role for Nitrite-Derived NO Hypertension, AHA Journals, 56 2 , Science of Nitric Oxide.
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Nitgic December 11, Protein-rich foods Though essential for mental Herbal medicine for urinary tract infections, Nitric Oxide is often a forgotten piece of the puzzle. Nitric Cognihive NO is an essential metabolic and vascular regulator that ajd naturally made in the body. Energy-boosting weight loss supplements is cogjitive unconventional neurotransmitter and intracellular messenger in the brain that increases blood flow and decreases blood pressure Kapil, V. et al. Supporting NO also improves vascular function and endothelial function, which may also provide protective benefits against the effects of COVID since the SARS-CoV-2 virus attacks endothelial function and this becomes a major cause of mortality. Overall, NO has a vital and positive effect on general health, mental health, the aging process, and even helps to repair skin damage. Do you Garcinia cambogia side effects go into a room at home and forget what ans Nitric oxide and cognitive function Nitriv When you Nitric oxide and cognitive function to Nitic you were doing earlier, do you Nitrif what you wanted in the other room? That is short-term memory loss. It is quite common as people grow older. However, if you or a loved one forget faces, places, names and even events that happened recently, that is a more serious memory loss that can only get worse. Some types of memory loss are linked to injury and they heal slowly.
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