scholarly journals Effects of Sleep Deprivation on the Tryptophan Metabolism

2020 ◽  
Vol 13 ◽  
pp. 117864692097090
Author(s):  
Abid Bhat ◽  
Ananda Staats Pires ◽  
Vanessa Tan ◽  
Saravana Babu Chidambaram ◽  
Gilles J Guillemin
Keyword(s):  
Sleep Deprivation ◽  
Kynurenic Acid ◽  
Second Messengers ◽  
Sleep Time ◽  
Kynurenine Pathway ◽  
Tryptophan Metabolism ◽  
Cellular Functions ◽  
Intracellular Second Messengers ◽  
The Impact ◽  
The Brain

Sleep has a regulatory role in maintaining metabolic homeostasis and cellular functions. Inadequate sleep time and sleep disorders have become more prevalent in the modern lifestyle. Fragmentation of sleep pattern alters critical intracellular second messengers and neurotransmitters which have key functions in brain development and behavioral functions. Tryptophan metabolism has also been found to get altered in SD and it is linked to various neurodegenerative diseases. The kynurenine pathway is a major regulator of the immune response. Adequate sleep alleviates neuroinflammation and facilitates the cellular clearance of metabolic toxins produced within the brain, while sleep deprivation activates the enzymatic degradation of tryptophan via the kynurenine pathway, which results in an increased accumulation of neurotoxic metabolites. SD causes increased production and accumulation of kynurenic acid in various regions of the brain. Higher levels of kynurenic acid have been found to trigger apoptosis, leads to cognitive decline, and inhibit neurogenesis. This review aims to link the impact of sleep deprivation on tryptophan metabolism and associated complication in the brain.

scholarly journals Effect of Sleep Deprivation on the Hippocampus of Adult and Senile Male Albino Rat: A Histological and Histochemical Study

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
S S I Elkilany ◽  
M M A Zakaria ◽  
R F Tash ◽  
A Y Mostafa ◽  
S W Abdelmalik ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Dentate Gyrus ◽  
Therapeutic Strategy ◽  
Control Group ◽  
Albino Rats ◽  
Free Access ◽  
Waste Products ◽  
Glymphatic System ◽  
The Impact ◽  
The Brain

Abstract Background The importance of sleep and the impact of its deprivation on development of brain pathology became a recent subject of interest in medicine. The restorative effect of sleep on the brain and the harmful effects of insomnia have been recently revealed through the discovery of the glymphatic system and its association with sleep. Aim of work Specific objectives are: To detect histological and apoptotic changes in the neurons and dendrites of the cornu Amonis and the dentate gyrus in sleep deprived rats in comparison to rats with undisturbed sleep pattern (control). To detect deposition of neurotoxic metabolites in comu Amonis and dentate gyrus in sleep deprived rats in comparison to controls. Methods Twenty four adult male Albino rats were used in the present experiment. randomly categorized into four equal groups; Group A1 served as the control group, Group .A2 one day sleep deprivation, Group A3 three days sleep deprivation and Group A4 seven days sleep deprivation. They were deprived of sleep using grid over water method where the animals placed over a grid suspended above tank filled with water with free access to food (rat chew) and water. Hippocampai specimens were collected, processed for paraffin blocks and examined by light microscopy. Results there were neurodegenerative signs appeared from day one sleep deprivation, increased by day three and prevailed by day seven. It was confirmed by apoptotic changes detected by caspase 3 immunohistochemical staining. Furthermore, deposition of beta amyloid appeared in rats deprived of sleep and confirmed by congo red stain. Conclusion Adequate sleep is essential for integrity of the newly discovered glymphatic system responsible for clearance of the brain from waste products including the area most involved in learning and memory function; the hippocampus. Correction of SD could be a viable therapeutic strategy to prevent the onset or slow the progression of AD. Recommendations Further characterization of the glymphatic system in humans are required, it may lead to new therapies and methods of prevention of neurodegenerative diseases. Correction of SD could be a viable therapeutic strategy to prevent the onset or slow the progression of AD.

scholarly journals Generation and characterization of a lysosomally targeted, genetically encoded Ca2+-sensor

2012 ◽  
Vol 449 (2) ◽  
pp. 449-457 ◽  
Author(s):  
Hannah V. McCue ◽  
Joanna D. Wardyn ◽  
Robert D. Burgoyne ◽  
Lee P. Haynes
Keyword(s):  
Second Messengers ◽  
Eukaryotic Cell ◽  
Endocytic Pathway ◽  
Cell Physiology ◽  
Simple Method ◽  
Late Endosomes ◽  
Intracellular Organelles ◽  
Intracellular Second Messengers ◽  
The Impact

Distinct spatiotemporal Ca2+ signalling events regulate fundamental aspects of eukaryotic cell physiology. Complex Ca2+ signals can be driven by release of Ca2+ from intracellular organelles that sequester Ca2+ such as the ER (endoplasmic reticulum) or through the opening of Ca2+-permeable channels in the plasma membrane and influx of extracellular Ca2+. Late endocytic pathway compartments including late-endosomes and lysosomes have recently been observed to sequester Ca2+ to levels comparable with those found within the ER lumen. These organelles harbour ligand-gated Ca2+-release channels and evidence indicates that they can operate as Ca2+-signalling platforms. Lysosomes sequester Ca2+ to a greater extent than any other endocytic compartment, and signalling from this organelle has been postulated to provide ‘trigger’ release events that can subsequently elicit more extensive Ca2+ signals from stores including the ER. In order to investigate lysosomal-specific Ca2+ signalling a simple method for measuring lysosomal Ca2+ release is essential. In the present study we describe the generation and characterization of a genetically encoded, lysosomally targeted, cameleon sensor which is capable of registering specific Ca2+ release in response to extracellular agonists and intracellular second messengers. This probe represents a novel tool that will permit detailed investigations examining the impact of lysosomal Ca2+ handling on cellular physiology.

scholarly journals Changes in the immune system in depression and dementia: causal or coincidental effects?

2006 ◽  
Vol 8 (2) ◽  
pp. 163-174 ◽  
Keyword(s):  
Neurotrophic Factors ◽  
Kynurenic Acid ◽  
Neuronal Damage ◽  
Later Life ◽  
Epidemiological Studies ◽  
Kynurenine Pathway ◽  
Pathological Changes ◽  
Induced Apoptosis ◽  
Inflammatory Changes ◽  
The Brain

Epidemiological studies show that there is a correlation between chronic depression and the likelihood of dementia in later life. There is evidence that inflammatory changes in the brain are pathological features of both depression and dementia. This suggests that an increase in inflammation-induced apoptosis, together with a reduction in the synthesis of neurotrophic factors caused by a rise in brain glucocorticoids, may play a role in the pathology of these disorders. A reduction in the neuroprotective components of the kynurenine pathway such as kynurenic acid, and an increase in the neurodegenerative components, 3-hydroxykynurenine and quinolinic acid, contribute to the pathological changes. Such changes are postulated to cause neuronal damage, and thereby predispose chronically depressed patients to dementia.

scholarly journals Kynurenines increase MRS metabolites in basal ganglia and decrease resting-state connectivity in frontostriatal reward circuitry in depression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiangchuan Chen ◽  
Diana J. Beltran ◽  
Valeriya D. Tsygankova ◽  
Bobbi J. Woolwine ◽  
Trusharth Patel ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Functional Connectivity ◽  
Resting State ◽  
Kynurenine Pathway ◽  
Self Report ◽  
Resonance Spectroscopy ◽  
Neural Function ◽  
Brain Chemistry ◽  
The Impact ◽  
The Brain

AbstractInflammation is associated with the development of anhedonia in major depression (MD), but the pathway by which inflammatory molecules gain access to the brain and lead to anhedonia is not clear. Molecules of the kynurenine pathway (KP), which is activated by inflammation, readily influx into the brain and generate end products that alter brain chemistry, disrupt circuit functioning, and result in the expression of inflammatory behaviors such as anhedonia. We examined the impact of plasma and CSF KP metabolites on brain chemistry and neural function using multimodal neuroimaging in 49 depressed subjects. We measured markers of glial dysfunction and distress including glutamate (Glu) and myo-inositol in the left basal ganglia using magnetic resonance spectroscopy (MRS); metrics of local activity coherence (regional homogeneity, ReHo) and functional connectivity from resting-state functional MRI measures; and anhedonia from the Inventory for Depressive Symptoms-Self Report Version (IDS-SR). Plasma kynurenine/tryptophan (KYN/TRP) ratio and cerebrospinal fluid (CSF) 3-hydroxykynurenine (3HK) were associated with increases in left basal ganglia myo-inositol. Plasma kynurenic acid (KYNA) and KYNA/QA were associated with decreases and quinolinic acid (QA) with increases in left basal ganglia Glu. Plasma and CSF KP were associated with decreases in ReHo in the basal ganglia and dorsomedial prefrontal regions (DMPFC) and impaired functional connectivity between these two regions. DMPFC-basal ganglia mediated the effect of plasma and CSF KP on anhedonia. These findings highlight the pathological impact of KP system dysregulation in mediating inflammatory behaviors such as anhedonia.

Role of Tryptophan-kynurenine Pathway in Depression: Psychopathological Aspect

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
A.-M. Myint
Keyword(s):  
Kynurenic Acid ◽  
Excitatory Amino Acid ◽  
Kynurenine Pathway ◽  
Response To Treatment ◽  
Excitatory Amino Acid Receptors ◽  
Amino Acid Receptors ◽  
Tryptophan Catabolism ◽  
Ifn Γ ◽  
The Brain

It was reported that cytokines such as IFN-γ reduce the synthesis of 5-HT by stimulating the activity of indoleamine 2,3 dioxygenase (IDO) enzyme which degrades tryptophan to kynurenine. Kynurenine is further metabolized to kynurenic acid (KYNA), 3-hydroxykynurenine (3OHK) and quinolinic acid (QA) by kynurenine aminotransferase (KAT), kynurenine 3-monooxygenase (KMO) and kynureninase. Both KMO and kynureninase are also shown to be activated by IFNγ. The 3OHK is neurotoxic apoptotic while QA is the excitotoxic N-methyl-D-aspartate (NMDA) receptor agonist. Conversely KYNA is an antagonist of all three ionotropic excitatory amino acid receptors and considered neuroprotective. In the brain, tryptophan catabolism occurs in the astrocytes and. The astrocytes are shown to produce mainly KYNA whereas microglia and macrophages produced mainly 3OHK and QA. The astrocytes have been demonstrated to metabolise the QA produced by the neighbouring microglia.Tryptophan breakdown has been found to be increased but KYNA, the neuroprotective metabolite is decreased in both blood and cerebrospinal fluid of the patients with major depression compared to healthy controls. Moreover, the ratio between KYNA and 3OHK showed significant correlation with response to treatment. These findings lead to the hypothesis an imbalance neuroprotection-neurodegener-ation in terms of kynurenine metabolites and their immunological and biochemical interactions in the brain might further induce the apoptosis of the neuroprotective astrocytes and the vulnerability to stress is thereby enhanced.

Kynurenic acid in brain function and dysfunction

2020 ◽  
pp. 323-332
Author(s):  
Robert Schwarcz ◽  
Sophie Erhardt
Keyword(s):  
Kynurenic Acid ◽  
Kynurenine Pathway ◽  
Psychotic Symptoms ◽  
Gabaergic Neurotransmission ◽  
Novel Approach ◽  
Healthy Control ◽  
Amino Acid Tryptophan ◽  
Persons With Schizophrenia ◽  
And Function ◽  
The Brain

The essential amino acid tryptophan is degraded primarily by the kynurenine pathway, a cascade of enzymatic steps leading to the generation of several neuroactive compounds. Of those, kynurenic acid (KYNA), an antagonist at N-methyl-D-aspartate (NMDA) and alpha7-nicotinic receptors, has gained much attention in schizophrenia research. The concentrations of both KYNA and its precursor, kynurenine, have been repeatedly found significantly elevated both in the postmortem cerebral cortex and in the cerebrospinal fluid of schizophrenia persons as compared to healthy control subjects. Studies in experimental animals have demonstrated that KYNA tightly controls dopaminergic, cholinergic, glutamatergic, and GABAergic neurotransmission, and elevated brain levels appear related to psychotic symptoms and cognitive impairments. The kyurenine pathway is highly inducible by immune activation, and studies have shown that the pro-inflammatory cytokines interleukin (IL)-1β‎ and IL-6 are elevated in schizophrenia and stimulate the production of KYNA. Another mechanism that may account for the abnormally high central kynurenine and KYNA levels seen in schizophrenia might be the observed reduced expression and activity of the enzyme kynurenine 3-monooxygenase (KMO), shunting the synthesis of kynurenine toward KYNA. In line with these studies and concepts, preclinical results suggest that inhibition of kynurenine aminotransferase (KAT) II, by reducing the synthesis and function of KYNA in the brain, offers a novel approach to ameliorate psychosis and to improve cognitive performance in persons with schizophrenia.

scholarly journals Effects of Tranilast on the Urinary Excretion of Kynurenic and Quinolinic Acid under Conditions of L Tryptophan Loading

2013 ◽  
Vol 6 ◽  
pp. IJTR.S12797 ◽  
Author(s):  
Rowland R. Noakes
Keyword(s):  
Urinary Excretion ◽  
Quinolinic Acid ◽  
Kynurenic Acid ◽  
Competitive Inhibitor ◽  
Kynurenine Pathway ◽  
Tryptophan Metabolism ◽  
Autoimmune Response ◽  
Current Therapy ◽  
Indoleamine 2 ◽  
Hydroxyanthranilic Acid

The pathogenesis of morphea and other cutaneous sclerosing disorders remain poorly understood. Although they are considered to be autoimmune disorders, abnormal tryptophan metabolism may be involved. Current therapy is directed to supressing the autoimmune response. Demonstration of a therapeutic response to manipulation of the kynurenine pathway would both support a role for abnormal tryptophan metabolism and offer additional targets for therapy. Tranilast is a 3-hydroxyanthranilic acid derivative known to target the kynurenine pathway. The aim of this study was to see if tranilast lowered the urinary excretion of the kynurenine metabolites kynurenic and quinolinic acid under condition of L tryptophan loading in a volunteer. Mean baseline value for kynurenic acid and quinolinic acid were 1.1 and 2.1 mmol/mol creatinine, respectively. This rose to 5.6 and 3.8 mmol/mol creatinine respectively under conditions of L tryptophan loading 2 grams daily. Adding 1 g of tranilast daily lowered the values to 2.0 and 2.9 mmol/mol creatinine, respectively. These data suggest that tranilast acts as a competitive inhibitor of either indoleamine 2, 3-dioxygenase (IDO), tryptophan 2, 3 di-oxygenase (TDO) or both. As it involved only 1 subject, the results may not be representative of the larger population and must be considered preliminary.

scholarly journals Intervensi Inklusif Sukan Terhadap Murid Gangguan Kecelaruan Tumpuan dan Hiperaktif (ADHD)

2020 ◽  
Vol 35 (2) ◽  
pp. 131-143
Author(s):  
Mohd Arshad Yahya ◽  
Mohd Firdaus Abdullah
Keyword(s):  
Sleep Time ◽  
Hyperactivity Disorder ◽  
Sport Activities ◽  
Long Time ◽  
Special Education Program ◽  
The Subject ◽  
The Individual ◽  
The Mind ◽  
The Impact ◽  
The Brain

Attention deficit/hyperactivity disorder (ADHD) is a form of disruption to the brain often experienced by growing children. ADHD children are often labelled as naughty by some. There are several forms of treatment that can be taken against this disorder such as the use of medication. However, the use of medicine will side effect such as loss appetite, disrupting sleep time and anxiety. This study was conducted by observing and recording anecdotes as a means of collecting data. The subject was an ADHD student who had undergone academic inclusiveness and also a special need athlete. The purpose of the study was to explore the effects of sports inclusive intervention on the negative, physical behaviour and social of the student. The findings of the study show that sports inclusion interventions can reduce the negative behaviour of ADHD students and can be an alternative to medication treatment. The effect of this intervention is more harmonious with no side effects and impact for a long time. Sports activities also have goals such as the Individual Teaching Plan concept. In Malaysia, sports intervention is quite new in the Integrated Special Education Program. The impact of this study is expected to open the mind of all parties to make sure that sport activities for special needs students is conducted for the purpose of treatment. The cooperation of all parties including parents is important in this alternative treatment.

scholarly journals Effects of Sleep Deprivation on the Brain Electrical Activity in Mice

2021 ◽  
Vol 11 (3) ◽  
pp. 1182
Author(s):  
Alexey N. Pavlov ◽  
Alexander I. Dubrovskii ◽  
Olga N. Pavlova ◽  
Oxana V. Semyachkina-Glushkovskaya
Keyword(s):  
Sleep Deprivation ◽  
Electrical Activity ◽  
Fluctuation Analysis ◽  
Brain Health ◽  
Short Term ◽  
Scaling Exponents ◽  
Sleep Deficit ◽  
The Impact ◽  
Detrended Fluctuation ◽  
The Brain

Sleep plays a crucial role in maintaining brain health. Insufficient sleep leads to an enhanced permeability of the blood–brain barrier and the development of diseases of small cerebral vessels. In this study, we discuss the possibility of detecting changes in the electrical activity of the brain associated with sleep deficit, using an extended detrended fluctuation analysis (EDFA). We apply this approach to electroencephalograms (EEG) in mice to identify signs of changes that can be caused by short-term sleep deprivation (SD). Although the SD effect is usually subject-dependent, analysis of a group of animals shows the appearance of a pronounced decrease in EDFA scaling exponents, describing power-law correlations and the impact of nonstationarity as a fairly typical response. Using EDFA, we revealed an SD effect in 9 out of 10 mice (Mann–Whitney test, p<0.05) that outperforms the DFA results (7 out of 10 mice). This tool may be a promising method for quantifying SD-induced pathological changes in the brain.

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