TY - JOUR
T1 - Unraveling Individual Differences in the HIV-1 Transgenic Rat
T2 - Therapeutic Efficacy of Methylphenidate
AU - McLaurin, Kristen A.
AU - Li, Hailong
AU - Booze, Rosemarie M.
AU - Fairchild, Amanda J.
AU - Mactutus, Charles F.
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41598-017-18300-2
DO - 10.1038/s41598-017-18300-2
M3 - Article
C2 - 29317696
AN - SCOPUS:85040465002
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 136
ER -
