title: Long term alterations in synaptic physiology, expression of β2 nicotinic receptors and ERK1/2 signaling in the hippocampus of rats with prenatal nicotine exposure.
abstract: Smoking during pregnancy is associated with long lasting, hippocampus dependent, cognitive deficits in children. The current study was performed to investigate the effect of prenatal nicotine exposure on excitatory synaptic physiology and cellular signaling in the hippocampus using a rodent model. Excitatory synaptic physiology was analyzed using electrophysiological methods to detect changes in synaptic plasticity, excitatory synaptic transmission and synaptic currents mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in the hippocampus. Additionally, western blot experiments were performed to quantify alterations in protein expression levels in the hippocampus. Prenatal nicotine exposure resulted in a decrease in long term potentiation (LTP) and an increase in long term depression (LTD). Basal synaptic transmission was also reduced with a concomitant decline in AMPAR mediated synaptic currents at the cellular and single channel levels. Presynaptic pool of vesicles docked close to release sites were also diminished in nicotine exposed rats. Moreover, reduced levels of β2 subunit containing nicotinic receptors and extracellular signal regulated kinase1/2 (ERK1/2) were observed in nicotine exposed rats. These results suggest that long lasting alterations in excitatory synaptic physiology, AMPAR synaptic currents and ERK1/2 signaling may serve as the molecular mechanisms for cognitive deficits associated with prenatal nicotine exposure.
authors.affiliation: Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, United States.
authors.forename: Kodeeswaran
authors.initials: K
authors.lastname: Parameshwaran
authors.forename: Manal A
authors.initials: MA
authors.lastname: Buabeid
authors.forename: Subhrajit
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Uthayathas
authors.forename: Thiruchelvam
authors.initials: T
authors.lastname: Kariharan
authors.forename: Muralikrishnan
authors.initials: M
authors.lastname: Dhanasekaran
authors.forename: Vishnu
authors.initials: V
authors.lastname: Suppiramaniam
mesh_terms: D000818:Animals; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D009538:Nicotine; D018091:Receptors, AMPA; D011978:Receptors, Nicotinic
keywords: AMPA receptors; Glutamate; Nicotinic receptors; Single channel; Synaptic plasticity