Medicine and Health Sciences Commons^™

The Association Between Fgf21 And Diabetic Erectile Dysfunction: Evidence From Clinical And Animal Studies, Song Yang, Yichun Zhang, Xiaohui Lyu, Yuanyuan Gu, Guodong Zhang, Pengcheng Liu, Yulu Zheng, Zheng Guo, Yanbo Zhang, Haifeng Hou

Research outputs 2022 to 2026

Erectile dysfunction (ED), a complication of diabetes mellitus (DM), affects 50–75% of men with diabetes. Fibroblast growth factor 21 (FGF21) is a liver-derived metabolic regulator which plays a role in insulin-independent glucose uptake in adipocytes. We designed a clinical study and an animal experiment to investigate the relationship between FGF21 and DM-induced ED. The clinical study enrolled 93 participants aged > 18 years (61 patients with type 2 DM and 32 healthy controls) from Taian City Central Hospital (TCCH) in Shandong Province, China, amongst whom the association between serum FGF21 and diabetic ED was analyzed. To further validate this association, we …

Pituitary Adenylate Cyclase-Activating Polypeptide Receptor Activation In The Hypothalamus Recruits Unique Signaling Pathways Involved In Energy Homeostasis, Brian Maunze, Katherine Wood Bruckner, Nikhil Nilesh Desai, Christopher Chen, Fanghong Chen, David Baker, Sujean Choi

Biomedical Sciences Faculty Research and Publications

Pituitary adenylate cyclase activating polypeptide (PACAP) exerts pleiotropic effects on ventromedial nuclei (VMN) of the hypothalamus and its control of feeding and energy expenditure through the type I PAC1 receptor (PAC1R). However, the endogenous role of PAC1Rs in the VMN and the downstream signaling responsible for PACAP’s effects on energy balance are unknown. Numerous studies have revealed that PAC1Rs are coupled to both Gαs/adenylyl cyclase/protein kinase A (Gαs/AC/PKA) and Gαq/phospholipase C/protein kinase C (Gαq/PLC/PKC), while also undergoing trafficking following stimulation. To determine the endogenous role of PAC1Rs and downstream signaling that may explain PACAP’s pleiotropic effects, we used RNA interference …

Antibodies Against Lysophosphatidic Acid Protect Against Blast-Induced Ocular Injuries, Peethambaran Arun, Franco Rossetti, James C. Demar, Ying Wang, Andrew B. Batuure, Donna M. Wilder, Irene D. Gist, Andrew J. Morris, Roger A. Sabbadini, Joseph B. Long

Internal Medicine Faculty Publications

Exposure to blast overpressure waves is implicated as the major cause of ocular injuries and resultant visual dysfunction in veterans involved in recent combat operations. No effective therapeutic strategies have been developed so far for blast-induced ocular dysfunction. Lysophosphatidic acid (LPA) is a bioactive phospholipid generated by activated platelets, astrocytes, choroidal plexus cells, and microglia and is reported to play major roles in stimulating inflammatory processes. The levels of LPA in the cerebrospinal fluid have been reported to increase acutely in patients with traumatic brain injury (TBI) as well as in a controlled cortical impact (CCI) TBI model in mice. …

The Regression Of Endometriosis With Glycosylated Flavonoids Isolated From Melilotus Officinalis (L.) Pall. In An Endometriosis Rat Model, Mert Ilhan, Zulfiqar Ali, Ikhlas A. Khan, Hakkı Taştan, Esra Küpeli Akkol

Faculty and Student Publications

© 2020 Objective: Melilotus officinalis (L.) Pall. is commonly used for treating bronchitis, painful menstruation, hemorrhoids, kidney stones, ulcers of the eyes, earache, and hardening and swelling of uterus. The European Medicines Agency reported the use of M. officinalis orally against stomach ache, gastric ulcer, and disorders of the liver and uterus in folk medicine. The present study aimed to appraise the activity of M. (L.) Pall. aerial parts in endometriosis rat model. Materials and methods: The endometriosis rat model was used to evaluate the potential activity of M. officinalis aerial parts based on its folkloric usage. The aerial parts …

Nanoparticle Brain Delivery: A Guide To Verification Methods, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Many reports conclude nanoparticle (NP) brain entry based on bulk brain analysis. Bulk brain includes blood, cerebrospinal fluid and blood vessels within the brain contributing to the blood-brain and blood-cerebrospinal fluid barriers. Considering the brain as neurons, glia and their extracellular space (brain parenchyma), most studies did not show brain parenchymal NP entry. Blood-brain and blood-cerebrospinal fluid barriers anatomy and function are reviewed. Methods demonstrating brain parenchymal NP entry are presented. Results demonstrating bulk brain versus brain parenchymal entry are classified. Studies are reviewed, critiqued and classified to illustrate results demonstrating bulk brain versus parenchymal entry. Brain, blood and peripheral …

A Review Of Rat Lungworm Infection And Recent Data On Its Definitive Hosts In Hawaii, Chris Niebuhr, Susan I. Jarvi, Shane R. Siers

USDA Wildlife Services: Staff Publications

Rat lungworm (Angiostrongylus cantonensis) is a zoonotic nematode that causes rat lungworm disease (angiostrongyliasis), a potentially debilitating form of meningitis, in humans worldwide. The definitive hosts for rat lungworm are primarily members of the genus Rattus, with gastropods as intermediate hosts. This parasite has emerged as an important public health concern in the United States, especially in Hawaii, where the number of human cases has increased in the last decade. Here we discuss the current knowledge of the rat lungworm, including information on the life cycle and host species, as well as updates on known infection levels. Three species of …

Crf Mediates Stress-Induced Pathophysiological High-Frequency Oscillations In Traumatic Brain Injury, Chakravarthi Narla, Paul S. Jung, Francisco Bautista Cruz, Michelle Everest, Julio Martinez-Trujillo, Michael O. Poulter

Physiology and Pharmacology Publications

Copyright © 2019 Narla et al. It is not known why there is increased risk to have seizures with increased anxiety and stress after traumatic brain injury (TBI). Stressors cause the release of corticotropin-releasing factor (CRF) both from the hypothalamic pituitary adrenal (HPA) axis and from CNS neurons located in the central amygdala and GABAergic interneurons. We have previously shown that CRF signaling is plastic, becoming excitatory instead of inhibitory after the kindling model of epilepsy. Here, using Sprague Dawley rats we have found that CRF signaling increased excitability after TBI. Following TBI, CRF type 1 receptor (CRFR1)-mediated activity caused …

Ephrin-B3 Controls Excitatory Synapse Density Through Cell-Cell Competition For Ephbs., Nathan T. Henderson, Sylvain J. Le Marchand, Martin Hruska, Simon Hippenmeyer, Liqun Luo, Matthew B. Dalva

Department of Neuroscience Faculty Papers

Cortical networks are characterized by sparse connectivity, with synapses found at only a subset of axo-dendritic contacts. Yet within these networks, neurons can exhibit high connection probabilities, suggesting that cell-intrinsic factors, not proximity, determine connectivity. Here, we identify ephrin-B3 (eB3) as a factor that determines synapse density by mediating a cell-cell competition that requires ephrin-B-EphB signaling. In a microisland culture system designed to isolate cell-cell competition, we find that eB3 determines winning and losing neurons in a contest for synapses. In a Mosaic Analysis with Double Markers (MADM) genetic mouse model system in vivo the relative levels of eB3 control …

Chemical Profile And In Vivo Toxicity Evaluation Of Unripe Citrus Aurantifolia Essential Oil, Christian K. Adokoh, Du-Bois Asante, Desmond O. Acheampong, Yohei Kotsuchibashi, Francis A. Armah, Ignatius H. Sirikyi, Keisuke Kimura, Edward Gmakame, Sey Abdul-Rauf

Research outputs 2014 to 2021

Citrus aurantifolia (Christm.) Swingle (syn. C. MEDICA var. ACIDA Brandis) (family: Rutaceae) essential oil is one of the cheapest oils found in local markets. Although, it is generally accepted as non-toxic to vital organs and cells, majority of people are cynical about it usage. Herein, the present study reports the chemical composition and in vivo oral toxicity study of unripe C. aurantifolia essential oil found in Ghana. The toxicity of C. aurantifolia essential oil extract was investigated via oral administration using two methods: The acute toxicity single dose study (SDS) and the repeated dose method. The oil exhibited no acute …

Validation And Optimisation Of A Touchscreen Progressive Ratio Test Of Motivation In Male Rats, Jonathan M. Hailwood, Christopher J. Heath, Trevor W. Robbins, Lisa M. Saksida, Timothy J. Bussey

Brain and Mind Institute Researchers' Publications

© 2018, The Author(s). Rationale: Across species, effort-related motivation can be assessed by testing behaviour under a progressive ratio (PR) schedule of reinforcement. However, to date, PR tasks for rodents have been available using traditional operant response systems only. Objectives: Touchscreen operant response systems allow the assessment of behaviour in laboratory rodents, using tasks that share high face validity with the computerised assessments used in humans. Here, we sought to optimise a rat touchscreen variant of PR and validate it by assessing the effects of a number of manipulations known to affect PR performance in non-touchscreen paradigms. Methods: Separate groups …

Map7 Regulates Axon Morphogenesis By Recruiting Kinesin-1 To Microtubules And Modulating Organelle Transport., Stephen R. Tymanskyj, Benjamin Yang, Kristen J. Verhey, Le Ma

Department of Neuroscience Faculty Papers

Neuronal cell morphogenesis depends on proper regulation of microtubule-based transport, but the underlying mechanisms are not well understood. Here, we report our study of MAP7, a unique microtubule-associated protein that interacts with both microtubules and the motor protein kinesin-1. Structure-function analysis in rat embryonic sensory neurons shows that the kinesin-1 interacting domain in MAP7 is required for axon and branch growth but not for branch formation. Also, two unique microtubule binding sites are found in MAP7 that have distinct dissociation kinetics and are both required for branch formation. Furthermore, MAP7 recruits kinesin-1 dynamically to microtubules, leading to alterations in organelle …

Mediodorsal Thalamic Neurons Mirror The Activity Of Medial Prefrontal Neurons Responding To Movement And Reinforcement During A Dynamic Dnmtp Task, Rikki L.A. Miller Phd, Miranda J. Francoeur, Brett M. Gibson, Robert G. Mair

Faculty Publications

The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making. We recorded MD neurons in rats performing a dynamic delayed nonmatching to position (dDNMTP) task and compared results to a previous study of mPFC with the same task (Onos et al., 2016). Criterion event-related responses were observed for 22% …

Subcutaneous Neurotophin 4 Infusion Using Osmotic Pumps Or Direct Muscular Injection Enhances Aging Rat Laryngeal Muscles, Richard D. Andreatta, Joseph C. Stemple, Tanya S. Seward, Colleen A. Mcmullen

Physical Therapy Faculty Publications

Laryngeal dysfunction in the elderly is a major cause of disability, from voice disorders to dysphagia and loss of airway protective reflexes. Few, if any, therapies exist that target age-related laryngeal muscle dysfunction. Neurotrophins are involved in muscle innervation and differentiation of neuromuscular junctions (NMJs). It is thought that neurotrophins enhance neuromuscular transmission by increasing neurotransmitter release. The neuromuscular junctions (NMJs) become smaller and less abundant in aging rat laryngeal muscles, with evidence of functional denervation. We explored the effects of NTF4 for future clinical use as a therapeutic to improve function in aging human laryngeal muscles. Here, we provide …

Bk Channels Mediate Synaptic Plasticity Underlying Habituation In Rats, Tariq Zaman, Cleusa De Oliveira, Mahabba Smoka, Chakravarthi Narla, Michael O. Poulter, Susanne Schmid

Anatomy and Cell Biology Publications

Habituation is a basic form of implicit learning and represents a sensory filter that is disrupted in autism, schizophrenia, and several other mental disorders. Despite extensive research in the past decades on habituation of startle and other escape responses, the underlying neural mechanisms are still not fully understood. There is evidence from previous studies indicating that BK channels might play a critical role in habituation. We here used a wide array of approaches to test this hypothesis. We show that BK channel activation and subsequent phosphorylation of these channels are essential for synaptic depression presumably underlying startle habituation in rats, …

Loss Of Displaced Starburst Amacrine Cells In A Rat Glaucoma Model, C A. Cooley-Themm, Q Ameel, David M. Linn, Cindy L. Linn

Peer Reviewed Articles

Acetylcholine (ACh) release by starburst amacrine cells (SACs) has been implicated in the production of retinal waves during early retinal development. Inhibitory gamma-aminobutyric acid (GABA) release by SACs is known to be involved in directional selectivity in the mature retina. However, the role of SAC release of ACh in the adult developed mammalian retina is not entirely understood. Some evidence suggests a neuroprotective effect on retinal ganglion cells (RGCs) acting through alpha7 nicotinic acetylcholine receptors (nAChRs) present in RGCs. If ACh released by SACs is neuroprotective to RGCs, it would follow that this cholinergic transmission might be compromised in glaucoma …

Improved Social Interaction, Recognition And Working Memory With Cannabidiol Treatment In A Prenatal Infection (Poly I:C) Rat Model, Ashleigh L. Osborne, Nadia Solowij, Ilijana Babic, Xu-Feng Huang, Katrina Weston-Green

Illawarra Health and Medical Research Institute

Neuropsychiatric disorders such as schizophrenia are associated with cognitive impairment, including learning, memory and attention deficits. Antipsychotic drugs are limited in their efficacy to improve cognition; therefore, new therapeutic agents are required. Cannabidiol (CBD), the non-intoxicating component of cannabis, has anti-inflammatory, neuroprotective and antipsychotic-like properties; however, its ability to improve the cognitive deficits of schizophrenia remains unclear. Using a prenatal infection model, we examined the effect of chronic CBD treatment on cognition and social interaction. Time-mated pregnant Sprague-Dawley rats (n=16) were administered polyinosinic-polycytidilic acid (poly I:C) (POLY; 4 mg/kg) or saline (CONT) at gestation day 15. Male offspring …

Intravenous Prenatal Nicotine Exposure Alters Meth-Induced Hyperactivity, Conditioned Hyperactivity, And Bdnf In Adult Rat Offspring, Ryan T. Lacy, Russell. W. Brown, Amanda J. Morgan, Charles F. Mactutus, Steven B. Harrod

ETSU Faculty Works

In the USA, approximately 15% of women smoke tobacco cigarettes during pregnancy. In utero tobacco smoke exposure produces somatic growth deficits like intrauterine growth restriction and low birth we

Rat Behavioral Discrimination Of Temporal Cues In Species-Specific Vocalization, Kevin Mathews Tharakan

Honors Scholar Theses

Current behavioral and neurophysiologic studies propose that many animals can detect and discriminate the invariant statistics found in natural vocalization (Geffen et. al., 2011; Rodriguez et al., 2010). However, according to current research the neuronal mechanisms underlying the sound discrimination process is still unclear. While numerous auditory statistics have been manipulated, none has varied the temporal and tonal frequency cues independently in their synthetic call sequences, thus it is still uncertain whether rats rely on temporal cues in the sound envelope for communication.

The aim of this research is to determine whether or not rats rely on temporal cues in …

A Model Of Blood Pressure, Heart Rate, And Vaso-Vagal Responses Produced By Vestibulo-Sympathetic Activation, Theodore Raphan, Bernard Cohen, Yongqing Xiang, Sergei B. Yakushin

Publications and Research

Blood Pressure (BP), comprised of recurrent systoles and diastoles, is controlled by central mechanisms to maintain blood flow. Periodic behavior of BP was modeled to study how peak amplitudes and frequencies of the systoles are modulated by vestibular activation. The model was implemented as a relaxation oscillator, driven by a central signal related to Desired BP. Relaxation oscillations were maintained by a second order system comprising two integrators and a threshold element in the feedback loop. The output signal related to BP was generated as a nonlinear function of the derivative of the first state variable, which is a summation …

Motor And Hippocampal Dependent Spatial Learning And Reference Memory Assessment In A Transgenic Rat Model Of Alzheimer's Disease With Stroke, Jennifer L. Au, Nina Weishaupt, Hayley J. Nell, Shawn N. Whitehead, David F. Cechetto

Anatomy and Cell Biology Publications

Alzheimer's disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk factor for AD, stroke has also been implicated as a risk factor and an exacerbating factor. The co-morbidity of stroke and AD results in worsened stroke-related motor control and AD-related cognitive deficits when compared to each condition alone. To model the combined condition of stroke and AD, a novel transgenic rat model of AD, with a mutated form of amyloid precursor protein (a key protein involved in the development of AD) incorporated into its DNA, is given a small …

Organization Of The Zone Of Transition Between The Pretectum And The Thalamus, With Emphasis On The Pretectothalamic Lamina, Emmanuel Marquez-Legorreta, Jose De Anchieta C. Horta-Junior, Albert S. Berrebi, Enrique Saldana

Faculty & Staff Scholarship

The zone of transition between the pretectum, derived from prosomere 1, and the thalamus, derived from prosomere 2, is structurally complex and its understanding has been hampered by cytoarchitectural and terminological confusion. Herein, using a battery of complementary morphological approaches, including cytoarchitecture, myeloarchitecture and the expression of molecular markers, we pinpoint the features or combination of features that best characterize each nucleus of the pretectothalamic transitional zone of the rat. Our results reveal useful morphological criteria to identify and delineate, with unprecedented precision, several [mostly auditory] nuclei of the posterior group of the thalamus, namely the pretectothalamic lamina (PTL; formerly …

Predicting Human Drug Toxicity And Safety Via Animal Tests: Can Any One Species Predict Drug Toxicity In Any Other, And Do Monkeys Help?, Jarrod Bailey, Michelle Thew, Michael Balls

Laboratory Experiments Collection

Animals are still widely used in drug development and safety tests, despite evidence for their lack of predictive value. In this regard, we recently showed, by producing Likelihood Ratios (LRs) for an extensive data set of over 3,000 drugs with both animal and human data, that the absence of toxicity in animals provides little or virtually no evidential weight that adverse drug reactions will also be absent in humans. While our analyses suggest that the presence of toxicity in one species may sometimes add evidential weight for risk of toxicity in another, the LRs are extremely inconsistent, varying substantially for …

A Non-Invasive Method To Evaluate Gastrointestinal Transit Behaviour In Rat, Geoffrey M. Bove

Biomedical Sciences Faculty Publications

Introduction: Many factors alter gastrointestinal transit. Animal models are useful for preclinical studies of gastrointestinal transit, but terminal methods do not allow later study, and stressful assessment methods will likely alter the transit of the animal. To overcome these factors, we developed a new method to assay rat total gastrointestinal transit.

Methods: Standard plastic cages with their bottoms cut off were placed on wire mesh floors. Custom apparatuses were built to contain fecal pellets as they fell through the floors. Webcams connected to a computer running a security program were placed to image the pellets at regular intervals. Custom food …

Nicotine Receptors Mediating Sensorimotor Gating And Its Enhancement By Systemic Nicotine, Farena Pinnock, Daniel Bosch, Tyler Brown, Nadine Simons, John R. Yeomans, Cleusa Deoliveira, Susanne Schmid

Anatomy and Cell Biology Publications

Prepulse inhibition (PPI) of startle occurs when intensity stimuli precede stronger startle-inducing stimuli by 10–1000 ms. PPI deficits are found in individuals with schizophrenia and other psychiatric disorders, and they correlate with other cognitive impairments. Animal research and clinical studies have demonstrated that both PPI and cognitive function can be enhanced by nicotine. PPI has been shown to be mediated, at least in part, by mesopontine cholinergic neurons that project to pontine startle neurons and activate muscarinic and potentially nicotine receptors (nAChRs). The subtypes and anatomical location of nAChRs involved in mediating and modulating PPI remain unresolved. We tested the …

A New Obesity Model Reveals The Hypophagic Properties Of Pacap Involve The Regulation Of Homeostatic Feeding In The Ventromedial Hypothalamic Nucleus And Hedonic Feeding In The Nucleus Accumbens, Matthew M. Hurley, Brian Maunze, Jon M. Resch, Mogen M. Frenkel, M. J. Reilley, Megan E. Block, David A. Baker, Sujean Choi

Biomedical Sciences Faculty Research and Publications

Binge eating in humans is a complex disorder that often involves discrete, compulsive feeding sessions of highly palatable foods even in the absence of a deprivation state or hunger. Binging can be effectively modeled in rodents by providing subjects with limited access to a palatable food source (Western Diet; WD) as an adjunct to ad lib access to normal chow (Standard Chow; SC). Although this design recapitulates several fundamental characteristics observed in binge eating disorder, the binge eating observed in this paradigm is likely a product of both hedonic and homeostatic drives with the need to balance energy stores still …

Saccharomyces Boulardii And Bismuth Subsalicylate As Low-Cost Interventions To Reduce The Duration And Severity Of Cholera, Johnathan Sheele, Jessica Cartowski, Angela Dart, Arjun Poddar, Shikha Gupta, Ajay Gupta

Computer Science Faculty Publications

We conducted a randomised single-blinded clinical trial of 100 cholera patients in Port-au-Prince, Haiti to determine if the probiotic Saccharomyces cerevisiae var. boulardii and the anti-diarrhoeal drug bismuth subsalicylate (BS) were able to reduce the duration and severity of cholera. Subjects received either: S. boulardii 250 mg, S. boulardii 250 mg capsule plus BS 524 mg tablet, BS 524 mg, or two placebo capsules every 6 hours alongside standard treatment for cholera. The length of hospitalisation plus the number and volume of emesis, stool and urine were recorded every 6 hours until the study subject was discharged (n=83), left against …

An Analysis Of The Use Of Animal Models In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls

Experimentation Collection

Animal use continues to be central to preclinical drug development, in spite of a lack of its demonstrable validity. The current nadir of new drug approvals and the drying-up of pipelines may be a direct consequence of this. To estimate the evidential weight given by animal data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive data set of 2,366 drugs, for which both animal and human data are available, including tissue-level effects and MedDRA Level 1–4 biomedical observations. This was done for three preclinical species (rat, mouse …

Heme Consumption Reduces Hepatic Triglyceride And Fatty Acid Accumulation In A Rat Model Of Nafld Fed Westernized Diet, Soon Yew Tang, Irwin Kee M. Cheah, Pei Ern Ng, Aina Hoi, Andrew M. Jenner

Illawarra Health and Medical Research Institute

Studies have identified that serum-free hemoglobin subunits correlate positively with the severity of nonalcoholic fatty liver disease (NAFLD). However, the role of hemoglobin in the development of NAFLD remains unclear. In the present study, a rat model of NAFLD was developed, using a westernized diet high in saturated fat and refined sugar. Since a "westernized" diet is also high in red meat, we tested the effect of hemoglobin as a dietary source of heme in our model. Sprague-Dawley rats were fed ad libitum for 4 weeks either control diet (7% fat), westernized diet (WD, 18% fat + 1% cholesterol), hemoglobin …

Interleukin-1 Receptor Antagonist Modulates Inflammation And Scarring After Ligament Injury, Connie S. Chamberlain, Ellen M. Leiferman, Kayt E. Frisch, Sarah E. Duenwald-Kuehl, Stacey L. Brickson, William L. Murphy, Georffrey S. Baer, Ray Vanderby

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

Ligaments have limited regenerative potential and as a consequence, repair is protracted and results in a mechanically inferior tissue more scar-like than native ligament. We previously reported that a single injection of interleukin-1 receptor antagonist (IL-1Ra) delivered at the time of injury, decreased the number of M2 macrophage-associated inflammatory cytokines. Based on these results, we hypothesized that IL-1Ra administered after injury and closer to peak inflammation (as would occur clinically), would more effectively decrease inflammation and thereby improve healing. Since IL-1Ra has a short half-life, we also investigated the effect of multiple injections. The objective of this study was to …

Oral Branched-Chain Amino Acid Supplements That Reduce Brain Serotonin During Exercise In Rats Also Lower Brain Catecholamines, Sujean Choi, Briana Disilvio, Madelyn H. Fernstrom, John D. Fernstrom

Biomedical Sciences Faculty Research and Publications

Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both …