Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion

Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE), a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound t...

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Bibliographic Details
Published in:PloS one 2016-01, Vol.11 (1), p.e0146540-e0146540
Main Authors: Namjoshi, Dhananjay R, Cheng, Wai Hang, Carr, Michael, Martens, Kris M, Zareyan, Shahab, Wilkinson, Anna, McInnes, Kurt A, Cripton, Peter A, Wellington, Cheryl L
Format: Article
Language:English
Subjects:
Alzheimer's disease
Anabolic Agents - pharmacology
Anabolic steroids
Androgens - pharmacology
Animals
Athletes
Atrophy
Axons - drug effects
Axons - pathology
Behavior
Binding sites
Biomechanics
Body weight
Brain
Brain Concussion - complications
Brain Concussion - pathology
Brain Injuries - complications
Brain Injuries - pathology
Brain Injury, Chronic - complications
Brain Injury, Chronic - pathology
Chronic brain injury
Chronic exposure
Chronic traumatic encephalopathy
Cognitive ability
Collaboration
Complications and side effects
Concussion
Dementia
Disease Models, Animal
Disease Progression
Dosage and administration
Drugs
Encephalopathy
Exposure
Fuel consumption
Head injuries
Health aspects
Immune response
Innate immunity
Laboratories
Localization
Male
Medicine
Methyltestosterone
Methyltestosterone - pharmacology
Mice
Mice, Inbred C57BL
Nandrolone - pharmacology
Neurodegenerative diseases
Neuropathology
Neurosciences
Nortestosterone
Pathogenesis
Pathology
Proteins
Risk factors
Serotonin S1 receptors
Steroid hormones
Steroids
Steroids - pharmacology
Substance use
Substantia alba
Tau protein
Testosterone
Testosterone - analogs & derivatives
Testosterone - pharmacology
Time Factors
Traumatic brain injury
Young adults
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Summary:Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE), a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound tauopathy. However, much remains to be learned about factors other than cumulative exposure that could influence concussion pathogenesis. Approximately 20% of CTE cases report a history of substance use including androgenic-anabolic steroids (AAS). How acute, chronic, or historical AAS use may affect the vulnerability of the brain to concussion is unknown. We therefore tested whether antecedent AAS exposure in young, male C57Bl/6 mice affects acute behavioral and neuropathological responses to mild traumatic brain injury (TBI) induced with the CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) platform. Male C57Bl/6 mice received either vehicle or a cocktail of three AAS (testosterone, nandrolone and 17α-methyltestosterone) from 8-16 weeks of age. At the end of the 7th week of treatment, mice underwent two closed-head TBI or sham procedures spaced 24 h apart using CHIMERA. Post-repetitive TBI (rTBI) behavior was assessed for 7 d followed by tissue collection. AAS treatment induced the expected physiological changes including increased body weight, testicular atrophy, aggression and downregulation of brain 5-HT1B receptor expression. rTBI induced behavioral deficits, widespread axonal injury and white matter microgliosis. While AAS treatment did not worsen post-rTBI behavioral changes, AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0146540