title: Nicotine attenuates the effect of HIV-1 proteins on the neural circuits of working and contextual memories.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV)-1-associated neurocognitive disorders (HAND) are characterized by synaptic damage and neuronal loss in the brain. Excessive glutamatergic transmission and loss of cholinergic neurons are the major indicators of HAND. Nicotine acts as a cholinergic channel modulator, and its cognitive-enhancing effect in neurodegenerative and cognitive disorders has been documented. However, it is unclear whether nicotine has any positive effect on memory and synaptic plasticity formation in HAND.
  
  
  METHODS
  We investigated the effects of nicotine on synaptic plasticity and hippocampus-prefrontal cortex (PFC)-amygdala-dependent memory formation in the HIV-1 transgenic (Tg) and F344 control rats.
  
  
  RESULTS
  Chronic nicotine treatment (0.4 mg/kg nicotine, base, subcutaneously) significantly attenuated the cognitive deficits in the HIV-1Tg rats in both the spatial and contextual fear memories but impaired the contextual learning memory in the F344 rats. To determine the role of nicotine in the synaptic dysfunction caused by HIV-1 proteins, we analyzed the expression of key representative genes related to synaptic plasticity in the hippocampus, PFC, and amygdala of the HIV-1Tg and F344 rats using a custom-designed qRT-PCR array. The HIV-1 proteins significantly altered the glutamate receptor-mediated intracellular calcium cascade and its downstream signaling cascade in a brain region-specific manner. Further, chronic nicotine treatment reversed the effect of HIV-1 proteins on the expression of genes involved in synaptic plasticity in the three brain regions. The effects of nicotine differed significantly in the HIV-1Tg and F344 rats.
  
  
  CONCLUSIONS
  Our findings indicate that nicotine can attenuate the effect of HIV viral proteins on cognitive function and produce a brain region- and strain-specific effect on the intracellular signaling cascades involved in synaptic plasticity and memory formation.
authors.affiliation: Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, 450 Ray C Hunt Drive, Suite G-170, Charlottesville, VA, 22903, USA.
authors.forename: Tanseli
authors.initials: T
authors.lastname: Nesil
authors.affiliation: Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, 450 Ray C Hunt Drive, Suite G-170, Charlottesville, VA, 22903, USA.
authors.forename: Junran
authors.initials: J
authors.lastname: Cao
authors.affiliation: Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, NJ, USA.
authors.forename: Zhongli
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Institute of NeuroImmune Pharmacology, Seton Hall University, South Orange, NJ, USA.|Department of Biological Sciences, Seton Hall University, South Orange, NJ, USA.
authors.forename: Sulie L
authors.initials: SL
authors.lastname: Chang
authors.affiliation: Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, 450 Ray C Hunt Drive, Suite G-170, Charlottesville, VA, 22903, USA. ml2km@virginia.edu.
authors.forename: Ming D
authors.initials: MD
authors.lastname: Li
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D015497:HIV-1 / Q000378:metabolism*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D008954:Models, Biological; D009434:Neural Pathways / Q000187:drug effects* / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics; D009538:Nicotine / Q000494:pharmacology*; D009928:Organ Specificity / Q000187:drug effects; D011916:Rats, Inbred F344; D055647:Rats, Transgenic; D015398:Signal Transduction / Q000187:drug effects; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D014764:Viral Proteins; D009538:Nicotine