title: Synaptic dysfunction in human immunodeficiency virus type-1-positive subjects: inflammation or impaired neuronal plasticity?
abstract: Many people infected with the human immunodeficiency virus type-1 (HIV) exhibit mild or severe neurological problems, termed HIV-associated neurocognitive disorder (HAND), even when receiving antiretroviral therapy. Thus, novel adjunctive therapies must be developed to overcome the neurotoxic effect of HIV. New therapies require a better understanding of the molecular and cellular mechanisms of HIV-induced neurotoxicity and the risk factors that, besides inflammation and T-cell depletion and drugs of abuse, render the central nervous system (CNS) a target of HIV-induced neurotoxicity. HIV appears to impair neuronal plasticity, which refers to the innate ability of the CNS respond to injury and promote recovery of function. The availability of brain-derived neurotrophic factor (BDNF), a potent neurotrophic factor that is present in abundance in the adult brain, is essential for neuronal plasticity. BDNF acts through a receptor system composed of Trk and p75NTR. Here, we present experimental evidence that some of the clinical features of HIV-mediated neurological impairment could result from altered BDNF/TrkB/p75NTR regulation and function.
authors.affiliation: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: V
authors.initials: V
authors.lastname: Avdoshina
authors.forename: A
authors.initials: A
authors.lastname: Bachis
authors.forename: I
authors.initials: I
authors.lastname: Mocchetti
mesh_terms: D015526:AIDS Dementia Complex / Q000503:physiopathology; D001370:Axonal Transport; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D019317:Evidence-Based Medicine; D015967:Gene Expression Regulation, Viral; D006679:HIV Seropositivity / Q000150:complications / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007249:Inflammation / Q000150:complications; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity; D020813:Receptor, trkB / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D012307:Risk Factors; D012720:Severity of Illness Index; D013569:Synapses; D009435:Synaptic Transmission
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D020813:Receptor, trkB