scholarly journals Potential Role of Neuroactive Tryptophan Metabolites in Central Fatigue: Establishment of the Fatigue Circuit

2020 ◽  
Vol 13 ◽  
pp. 117864692093627
Author(s):  
Masatoshi Yamashita
Keyword(s):  
Social Life ◽  
Potential Role ◽  
Memory Function ◽  
Dynamic Change ◽  
Central Fatigue ◽  
Brain Regions ◽  
Kynurenine Pathway ◽  
Treadmill Running ◽  
Brain Functions ◽  
Tryptophan Metabolites

Central fatigue leads to reduced ability to perform mental tasks, disrupted social life, and impaired brain functions from childhood to old age. Regarding the neurochemical mechanism, neuroactive tryptophan metabolites are thought to play key roles in central fatigue. Previous studies have supported the “tryptophan-serotonin enhancement hypothesis” in which tryptophan uptake into extensive brain regions enhances serotonin production in the rat model of exercise-induced fatigue. However, serotonin was transiently released after 30 minutes of treadmill running to exhaustion, but this did not reflect the duration of fatigue. In addition, as the vast majority of tryptophan is metabolized along the kynurenine pathway, possible involvement of the tryptophan-kynurenine pathway in the mechanism of central fatigue induction has been pointed out. More recently, our study demonstrated that uptake of tryptophan and kynurenine derived from the peripheral circulation into the brain enhances kynurenic acid production in rat brain in sleep deprivation–induced central fatigue, but without change in serotonin activity. In particular, dynamic change in glial-neuronal interactive processes within the hypothalamus-hippocampal circuit causes central fatigue. Furthermore, increased tryptophan-kynurenine pathway activity in this circuit causes reduced memory function. This indicates a major potential role for the endogenous tryptophan-kynurenine pathway in central fatigue, which supports the “tryptophan-kynurenine enhancement hypothesis.” Here, we review research on the basic neuronal mechanism underlying central fatigue induced by neuroactive tryptophan metabolites. Notably, these basic findings could contribute to our understanding of latent mental problems associated with central fatigue.

scholarly journals Exploitation of the IDO Pathway in the Therapy of Rheumatoid Arthritis

2013 ◽  
Vol 6s1 ◽  
pp. IJTR.S11737 ◽  
Author(s):  
Richard O. Williams
Keyword(s):  
Rheumatoid Arthritis ◽  
Anthranilic Acid ◽  
Kynurenine Pathway ◽  
Gene Encoding ◽  
Rate Limiting Step ◽  
Tryptophan Metabolites ◽  
Synthetic Derivative ◽  
Rate Limiting ◽  
Kinetics Of ◽  
Draining Lymph Nodes

Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting step along the kynurenine pathway and is thought to play a key role in immune homeostasis through depletion of tryptophan and accumulation of kynurenines. In this review we summarize recent research into the possibility of harnessing the IDO pathway for the therapy of rheumatoid arthritis. Inhibition of IDO activity, or knockout of the gene encoding IDO, was shown to cause an increase in the severity of collagen-induced arthritis, an animal model of rheumatoid arthritis. The increased severity of disease was associated with elevated numbers of pathogenic Th1 and Th17 cells in the joints and draining lymph nodes. In another study, analysis of the kinetics of expression of downstream kynurenine pathway enzymes during the course of arthritis revealed a potential role for tryptophan metabolites in resolution of arthritis. Furthermore, the therapeutic administration of L-kynurenine or [3,4-dimethoxycinnamonyl]-anthranilic acid (a synthetic derivative of 3-hydroxy-anthranilic acid) significantly reduced both clinical and histological progression of experimental arthritis. These findings raise the possibility of exploiting the IDO pathway for the therapy of autoimmune disease.

Abstract P730: MCA Stroke Chronically Disrupts Hippocampal Activity and Cortico-Hippocampal Communication

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Zachary Ip ◽  
Gratianne Rabiller ◽  
Jiwei He ◽  
Shivalika Chavan ◽  
Yasuo Nishijima ◽  
...  
Keyword(s):  
Structural Integrity ◽  
Memory Function ◽  
Brain Regions ◽  
Male Rats ◽  
Brain State ◽  
Signal Power ◽  
Hippocampal Function ◽  
Electrode Arrays ◽  
Mca Occlusion ◽  
Hippocampal Activity

Introduction: Cognition and memory deficits are common sequelae following middle cerebral artery (MCA) stroke, one of the most common strokes in humans. However MCA stroke does not compromise the structural integrity of the hippocampus, which is highly involved in memory function, because the MCA does not supply blood flow to the hippocampus. We previously reported on the acute effect of MCA stroke, where we observed increased hippocampal activity and cortico-hippocampal communication. Here we investigate chronic changes to local oscillations and cortico-hippocampal communication following MCA occlusion in rats two weeks and one month following stroke. Hypothesis: Cortical stroke affects remote brain regions, disrupting hippocampal function and cortico-hippocampal communication. Methods: We subjected male rats (n=28) to distal MCA occlusion compared to controls (n=19). We recorded local field potentials simultaneously from cortex and hippocampus two weeks and one month following stroke using 16-site linear electrode arrays under urethane anesthesia. We analyzed signal power, brain state, CFC, and sharp wave SPW-Rs to assess hippocampal function and cortico-hippocampal communication. Results: Our results show disruptions to local oscillations; lowered delta (1-3 Hz) signal power in the cortex and hippocampus, increased signal power in gamma (30-60 Hz) and high gamma (60-200 Hz) in cortex and hippocampus. Theta/delta brain state is disrupted, and SPW-Rs increase in power at two weeks, before returning to baseline levels at one month. Communication is also disrupted; Theta-gamma coupling, a measure of information being communicated between regions, breaks down after stroke. Conclusions: These results suggest that chronic stroke causes significant changes to hippocampal function, which can be characterized by these electrophysiological biomarkers, establishing putative targets for targeted stimulation therapies.

Until Death Do Us Part and They Upload Us Into Clones: An Analysis of Film Narratives About Mind Uploading and the Myth of Immortality

2021 ◽  
Vol 16 (2) ◽  
pp. 529-548
Author(s):  
Anja Zlatović ◽  
Keyword(s):  
Science Fiction ◽  
Social Life ◽  
Modern Society ◽  
Eternal Life ◽  
Fear Of Death ◽  
Brain Functions ◽  
Technological Advances ◽  
Visual Science ◽  
The Mind ◽  
Tv Show

The fear of death and the myth of immortality are themes long present in various narratives, whether literary or visual. Science fiction as a genre offers us many venues for new explorations of this idea. Mind uploading is one of them. This fictional technique, related to cloning, is performed when the mind and consciousness of a person are transferred to another biological body or machine with the help of technology. In this way, a person continues their social life through their brain functions. This paper looks at four separate recent screen narratives – the movies Self/less, Transcendence, and Replicas, and the episode “Be Right Back” of the TV show Black Mirror. With the help of Tzvetan Todorov’s structural analysis, we find clauses that are present in all of the plots and see what ideas and topics they share. The paper also uses the idea of anthropological reading of science fiction and therefore uses scientific research to analyze these themes. By looking at anthropological findings of immortality, mortality, death in modern society, and digital techniques, we see how the analyzed narratives portray a unique mixture of fear of and longing for all the mentioned processes and ideas. Finally, this paper shows how science fiction could possibly reflect reality – both through presenting thoughts of society and inspiring future technological advances and ideas (in this case, the quest for immortality). While humans are still far from achieving eternal life, the mentioned screen narratives portray the growing stream of ideas that deal with mind uploading in the age of the internet and social media.

scholarly journals Genetic and Neuroimaging Approaches to Understanding Post-Traumatic Stress Disorder

2020 ◽  
Vol 21 (12) ◽  
pp. 4503
Author(s):  
Sabah Nisar ◽  
Ajaz A. Bhat ◽  
Sheema Hashem ◽  
Najeeb Syed ◽  
Santosh K. Yadav ◽  
...  
Keyword(s):  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Memory Function ◽  
Deep Understanding ◽  
Brain Regions ◽  
Post Traumatic Stress ◽  
Brain Areas ◽  
Social Burden ◽  
Post Traumatic

Post-traumatic stress disorder (PTSD) is a highly disabling condition, increasingly recognized as both a disorder of mental health and social burden, but also as an anxiety disorder characterized by fear, stress, and negative alterations in mood. PTSD is associated with structural, metabolic, and molecular changes in several brain regions and the neural circuitry. Brain areas implicated in the traumatic stress response include the amygdala, hippocampus, and prefrontal cortex, which play an essential role in memory function. Abnormalities in these brain areas are hypothesized to underlie symptoms of PTSD and other stress-related psychiatric disorders. Conventional methods of studying PTSD have proven to be insufficient for diagnosis, measurement of treatment efficacy, and monitoring disease progression, and currently, there is no diagnostic biomarker available for PTSD. A deep understanding of cutting-edge neuroimaging genetic approaches is necessary for the development of novel therapeutics and biomarkers to better diagnose and treat the disorder. A current goal is to understand the gene pathways that are associated with PTSD, and how those genes act on the fear/stress circuitry to mediate risk vs. resilience for PTSD. This review article explains the rationale and practical utility of neuroimaging genetics in PTSD and how the resulting information can aid the diagnosis and clinical management of patients with PTSD.

scholarly journals Sex in the brain: hormones and sex differences

2016 ◽  
Vol 18 (4) ◽  
pp. 373-383 ◽  
Keyword(s):  
Sex Differences ◽  
Sex Hormones ◽  
Genetic Factors ◽  
Motor Coordination ◽  
Brain Regions ◽  
New Era ◽  
Brain Functions ◽  
Opioid Sensitivity ◽  
Males And Females ◽  
The Brain

Contrary to popular belief, sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Many neural and behavioral functions are affected by estrogens, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences, and responses to sex hormones in brain regions and upon functions not previously regarded as subject to such differences, indicate that we are entering a new era in our ability to understand and appreciate the diversity of gender-related behaviors and brain functions.

scholarly journals Establishment of a Highly Sensitive Analytical Method For Measurement of Monoamine Neurotransmitters Using Mass Spectrometry

2021 ◽  
Author(s):  
Anri Hirai ◽  
Ryo Yamazaki ◽  
Atsushi Kobayashi ◽  
Takashi Kimura ◽  
Kei Nomiyama ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Body Weight ◽  
Analytical Method ◽  
Brain Regions ◽  
Liquid Chromatography Mass Spectrometry ◽  
Monoamine Neurotransmitters ◽  
Chemical Substances ◽  
Brain Functions ◽  
Spontaneous Movements ◽  
Highly Sensitive

Abstract Monoamine neurotransmitters (MAs), including dopamine (DA) and serotonin (5-HT), regulate brain functions such as behavior, memory, and learning. Neonicotinoids are pesticides that are being used more frequently. Neonicotinoid exposure has been observed to produce neurological symptoms, such as altered spontaneous movements and anxiety-like behaviors, which are suspected to be caused by altered MA levels. However, current neurotoxicity tests are not sufficiently sensitive to make these determinations. In this study, we performed some behavior tests and developed a sensitive and accurate analytical method using liquid chromatography-mass spectrometry (LC-MS/MS) to clarify the effects of neonicotinoid administration on MAs in the brain.We orally administered the neonicotinoid imidacloprid (0, 10, and 50 mg/kg body weight) to C57BL/6NCrSlc mice. In behavior tests, the decrease of activity was observed. The LC-MS/MS quantification of MAs in various brain regions by tetrafluoroborate salt of 2,4-diphenyl-pyranylium (DPP) derivatization, which was newly developed in this study, showed a decrease in some MA levels in the olfactory bulb and the striatum.Thus, in this study, we developed a new method for the sensitive detection of MAs by LC/MS using DPP derivatization. In addition, we showed that this sensitive MA quantification is effective in clarifying the neurotoxicity caused by chemical substances.

scholarly journals Acute stress enhances adult rat hippocampal neurogenesis and activation of newborn neurons via secreted astrocytic FGF2

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Elizabeth D Kirby ◽  
Sandra E Muroy ◽  
Wayne G Sun ◽  
David Covarrubias ◽  
Megan J Leong ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Acute Stress ◽  
Memory Function ◽  
Brain Regions ◽  
Hippocampal Neurogenesis ◽  
Mammalian Brain ◽  
Stress Hormone ◽  
Adult Rat ◽  
Neural Stem Progenitor Cells ◽  
Newborn Neurons

Stress is a potent modulator of the mammalian brain. The highly conserved stress hormone response influences many brain regions, particularly the hippocampus, a region important for memory function. The effect of acute stress on the unique population of adult neural stem/progenitor cells (NPCs) that resides in the adult hippocampus is unclear. We found that acute stress increased hippocampal cell proliferation and astrocytic fibroblast growth factor 2 (FGF2) expression. The effect of acute stress occurred independent of basolateral amygdala neural input and was mimicked by treating isolated NPCs with conditioned media from corticosterone-treated primary astrocytes. Neutralization of FGF2 revealed that astrocyte-secreted FGF2 mediated stress-hormone-induced NPC proliferation. 2 weeks, but not 2 days, after acute stress, rats also showed enhanced fear extinction memory coincident with enhanced activation of newborn neurons. Our findings suggest a beneficial role for brief stress on the hippocampus and improve understanding of the adaptive capacity of the brain.

scholarly journals STAB: a spatio-temporal cell atlas of the human brain

2020 ◽  
Vol 49 (D1) ◽  
pp. D1029-D1037
Author(s):  
Liting Song ◽  
Shaojun Pan ◽  
Zichao Zhang ◽  
Longhao Jia ◽  
Wei-Hua Chen ◽  
...  
Keyword(s):  
Human Brain ◽  
Single Cell ◽  
Temporal Dynamics ◽  
Cell Types ◽  
Brain Regions ◽  
Molecular Characteristics ◽  
Great Effort ◽  
Brain Functions ◽  
Spatio Temporal ◽  
The Brain

Abstract The human brain is the most complex organ consisting of billions of neuronal and non-neuronal cells that are organized into distinct anatomical and functional regions. Elucidating the cellular and transcriptome architecture underlying the brain is crucial for understanding brain functions and brain disorders. Thanks to the single-cell RNA sequencing technologies, it is becoming possible to dissect the cellular compositions of the brain. Although great effort has been made to explore the transcriptome architecture of the human brain, a comprehensive database with dynamic cellular compositions and molecular characteristics of the human brain during the lifespan is still not available. Here, we present STAB (a Spatio-Temporal cell Atlas of the human Brain), a database consists of single-cell transcriptomes across multiple brain regions and developmental periods. Right now, STAB contains single-cell gene expression profiling of 42 cell subtypes across 20 brain regions and 11 developmental periods. With STAB, the landscape of cell types and their regional heterogeneity and temporal dynamics across the human brain can be clearly seen, which can help to understand both the development of the normal human brain and the etiology of neuropsychiatric disorders. STAB is available at http://stab.comp-sysbio.org.

scholarly journals Maternal Dietary Docosahexaenoic Acid Alters Lipid Peroxidation Products and (n-3)/(n-6) Fatty Acid Balance in Offspring Mice

Metabolites ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 40 ◽  
Author(s):  
Bo Yang ◽  
Runting Li ◽  
Taeseon Woo ◽  
Jimmy Browning ◽  
Hailong Song ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Docosahexaenoic Acid ◽  
Maternal Diet ◽  
Brain Regions ◽  
Diet Group ◽  
Mammalian Brain ◽  
Enzymatic Reactions ◽  
Functional Changes ◽  
Lipid Peroxidation Products ◽  
Brain Functions

The abundance of docosahexaenoic acid (DHA) in the mammalian brain has generated substantial interest in the search for its roles in regulating brain functions. Our recent study with a gene/stress mouse model provided evidence to support the ability for the maternal supplement of DHA to alleviate autism-associated behavior in the offspring. DHA and arachidonic acid (ARA) are substrates of enzymatic and non-enzymatic reactions, and lipid peroxidation results in the production of 4-hydroxyhexenal (4-HHE) and 4-hydroxynonenal (4-HNE), respectively. In this study, we examine whether a maternal DHA-supplemented diet alters fatty acids (FAs), as well as lipid peroxidation products in the pup brain, heart and plasma by a targeted metabolite approach. Pups in the maternal DHA-supplemented diet group showed an increase in DHA and a concomitant decrease in ARA in all brain regions examined. However, significant increases in 4-HHE, and not 4-HNE, were found mainly in the cerebral cortex and hippocampus. Analysis of heart and plasma showed large increases in DHA and 4-HHE, but a significant decrease in 4-HNE levels only in plasma. Taken together, the DHA-supplemented maternal diet alters the (n-3)/(n-6) FA ratio, and increases 4-HHE levels in pup brain, heart and plasma. These effects may contribute to the beneficial effects of DHA on neurodevelopment, as well as functional changes in other body organs.

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