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Abnormal dopamine synapses in HIV‐1 infection drive circuit specific neurocognitive impairment
Author(s) -
Gelman Benjamin B,
Soukup Vicki M
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.173.9
Subject(s) - neuroscience , dopamine , dopamine receptor d2 , striatum , prefrontal cortex , dorsolateral prefrontal cortex , dopamine transporter , postsynaptic potential , tyrosine hydroxylase , psychology , biology , medicine , receptor , dopaminergic , cognition
Dopamine synapses in HIV infected autopsy brains from the NNTC were analyzed neurochemically. DAergic markers in striatum of decedents with HIV encephalitis (HIVE) were abnormal. Presynaptic dopamine reuptake transporter (DAT1) increased; tyrosine hydroxylase decreased. Postsynaptic dopamine type 2 (D2R) receptor mRNA and protein were decreased with parallel decreases in downstream events including dynorphin and enkephalin expression. To determine if DAergic tone is dynamically changed in other circuits, synapses were examined in the dorsolateral prefrontal cortex (DLPFC) because they drive executive function and working memory. D2R receptor expression and downstream changes were increased in DLPFC, precisely opposite to striatum. Performance was examined for a test of working memory and executive function that specifically drives DAergic circuits in DLPFC (WCST). Increased D2R expression in DLPFC was strongly linked with poor performance on WCST, and also with HIV loading in cerebrospinal fluid. This is the first clinicopathological autopsy illustration that abnormal behavior associated with HIV infection is linked with DAergic dysfunction, and that the DAergic disturbances are circuit specific.