Behavioural brain research
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Thalamic dysfunction has been implicated in overall chronic neurological dysfunction after traumatic brain injury (TBI), however little is known about the underlying histopathology. In experimental diffuse TBI (dTBI), we hypothesize that persisting histopathological changes in the ventral posteromedial (VPM) nucleus of the thalamus is indicative of progressive circuit reorganization. Since circuit reorganization in the VPM impacts the whisker sensory system, the histopathology could explain the development of hypersensitivity to whisker stimulation by 28days post-injury; similar to light and sound hypersensitivity in human TBI survivors. ⋯ These data indicate that dTBI results in persisting thalamic histopathology out to a chronic time point. While these changes can be indicative of either adaptive (recovery) or maladaptive (neurological dysfunction) circuit reorganization, they also provide a potential mechanism by which maladaptive circuit reorganization could contribute to the development of chronic neurological dysfunction. Understanding the processes that mediate circuit reorganization is critical to the development of future therapies for TBI patients.
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The postconcussion syndrome following mild traumatic brain injuries (mTBI) has been regarded as a mostly benign syndrome that typically resolves in the immediate months following injury. However, in some individuals, symptoms become chronic and persistent. This has been a striking feature of the mostly blast-related mTBIs that have been seen in veterans returning from the recent conflicts in Iraq and Afghanistan. ⋯ Fewer animal studies have addressed the chronic effects of lower level blast exposures that are more comparable to those involved in human mTBI or subclinical blast. Here we describe a rat model of repetitive low-level blast exposure that induces a variety of anxiety and PTSD-related behavioral traits including exaggerated fear responses that were present when animals were tested between 28 and 35 weeks after the last blast exposure. These animals provide a model to study the chronic and persistent behavioral effects of blast including the relationship of PTSD to mTBI in dual diagnosis veterans.
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We previously identified a novel molecule, SHATI/NAT8L, as having an inhibitory effect on methamphetamine dependence. We generated Shati/Nat8l knockout (KO) mice and found that they showed neurochemical changes and behavioral abnormalities related to attention deficit/hyperactivity disorder (AD/HD). In this study, we assessed validities of the Shati/Nat8l KO mice as a new animal model for AD/HD through a behavioral pharmacology approach. ⋯ As the result, almost all behavioral deficits were improved by the treatment of both ATX and MPH. Our findings suggest that Shati/Nat8l KO mice have an impaired neural system similar to AD/HD pathophysiology. Shati/Nat8l KO mice might serve as a novel and a useful animal model for the pathophysiology of AD/HD.
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Clinical and pre-clinical studies indicate that exercise is beneficial to many aspects of brain function especially during aging. The present study investigated the effects of a treadmill running protocol in young (3month-old) and aged (22month-old) male Wistar rats, on: I) cognitive function, as assessed by spatial reference memory in the Morris water maze; II) oxidative stress parameters and the expression of neurotrophic factors BDNF, NT-3, IGF-1 and VEGF in the hippocampus. ⋯ Results demonstrate that the moderate treadmill running exercise: I) prevented age-related deficits in reference memory in the Morris water maze; II) prevented the age-related increase of reactive oxygen species levels and lipid peroxidation in the hippocampus; III) caused an increase of BDNF, NT-3 and IGF-1 expression in the hippocampus of aged rats. Taken together, results suggest that both exercise molecular effects, namely the reduction of oxidative stress and the increase of neurotrophic factors expression in the hippocampus, might be related to its positive effect on memory performance in aged rats.
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Glutamatergic system has an important role in cocaine-seeking behavior. Studies have reported that chronic exposure to cocaine induces downregulation of glutamate transporter-1 (GLT-1) and cystine/glutamate exchanger (xCT) in the central reward brain regions. Ceftriaxone, a β-lactam antibiotic, restored GLT-1 expression and consequently reduced cue-induced reinstatement of cocaine-seeking behavior. ⋯ Importantly, AMP/SUL treatment normalized GLT-1 and xCT expression in the NAc core and shell; however, the drug normalized mGluR1 expression in the NAc core only. Additionally, AMP/SUL increased the expression of GLT-1 and xCT in the dmPFC as compared to the water naïve group. These findings demonstrated that glial glutamate transporters and mGluR1 in the mesocorticolimbic area could be potential therapeutic targets for the attenuation of reinstatement to cocaine-seeking behavior.