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  • 标题:Unraveling Individual Differences In The HIV-1 Transgenic Rat: Therapeutic Efficacy Of Methylphenidate
  • 本地全文:下载
  • 作者:Kristen A. McLaurin ; Hailong Li ; Rosemarie M. Booze
  • 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.
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