文章基本信息

标题：Unraveling Individual Differences In The HIV-1 Transgenic Rat: Therapeutic Efficacy Of Methylphenidate
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作者：Kristen A. McLaurin ; Hailong Li ; Rosemarie M. Booze 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：136
DOI：10.1038/s41598-017-18300-2
语种：English
出版社：Springer Nature
摘要：Despite the heterogeneity of HIV-1 associated neurocognitive disorders (HAND), assignment of categorical diagnoses based on the level of impairment (e.g., Frascati criteria) obfuscates the well-acknowledged variability observed within the population of HIV-1+ individuals. The present study sought to elucidate the natural heterogeneity in adult HIV-1 transgenic (Tg) rats using three interrelated aims. First, heterogeneity of the HIV-1 transgene was examined using a pretest-posttest design to assess therapeutic efficacy of oral self-administration (OSA) of methylphenidate (MPH; 2.4 ± 0.2 mg/kg), targeting neurotransmitter alterations in HIV-1, on temporal processing. Approximately 42% of HIV-1 Tg animals displayed an improvement in temporal processing following OSA of MPH. Second, repeated OSA of MPH (22-27 days) altered dendritic spine morphology in layer II-III pyramidal neurons in the medial prefrontal cortex. HIV-1 Tg animals exhibited a population shift towards longer spines with decreased head diameter on lower order branches; a shift associated with temporal processing impairment. Third, in HIV-1 Tg animals, dendritic spine backbone length (µm) was associated with temporal processing impairment; a brain/behavior relationship not observed in control animals. Assessing the therapeutic efficacy of MPH revealed heterogeneity in the neural mechanisms underlying neurocognitive impairments, providing a key target for individualized therapeutic and diagnostic approaches for HAND.