Sex-specific effects of chronic neonatal nicotine exposure on hippocampal development and long-term repercussions for hippocampal function : a dissertation /
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| Format: | Thesis Book |
| Language: | English |
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[College Station, Tex.] :
[Texas A&M University System Health Science Center],
[2012]
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| Abstract: | ABSTRACT: Prenatal exposure to nicotine via maternal smoking has been linked to behavioral and cognitive difficulties later in life, suggesting that developmental nicotine exposure may result in long-lasting functional deficits. Our lab has developed a chronic neonatal nicotine (CNN) treatment model that uses gastric intubation to administer 6 mg/kg/day of nicotine in milk formula or milk formula only (Control) to rat pups from postnatal day (P)1-P7. We tested whether neonatal nicotine exposure affects hippocampal development and results in long-lasting changes in hippocampal function. Initially, we recorded extracellular field potentials in hippocampal slices from young adult (P60-90) male and female rats. We found that CNN treatment resulted in an increase in baseline excitation in males, and larger responses to the GABA[subscript A]R antagonist bicuculline in both male and female rats. These results suggest that CNN treatment produces long-lasting changes that alter the excitation/inhibition ratio within the hippocampus, with males being affected to a greater extent. To determine possible causes, mRNA expression of key proteins involved in the development of the GABAergic and glutamatergic systems were examined by in situ hybridization in Control- and CNN-treated pups at P5 and P8. We found that CNN treatment results in an increase in the mRNA expression of BDNF and the K[superscript +]/Cl[superscript -] co-transporter KCC2 in P5 male but not female hippocampus, suggesting that maturation of the GABAergic system may be altered. Because males appeared to be more sensitive to our CNN treatment, we used patch-clamp recordings from CA1 pyramidal cells from hippocampal slices to more closely examine inhibitory and excitatory synaptic transmission in the 60-90 day old male rats. CNN treatment resulted in increased frequency of spontaneous postsynaptic currents and miniature inhibitory postsynaptic currents (mIPSCs) compared to control males. Acute nicotine increased the frequency of mIPSCs over a greater range of concentrations in Control- versus CNN-treated rats. CNN treatment also resulted in larger AMPA receptor-mediated evoked excitatory postsynaptic currents, and an abscence of nicotine-induced reductions in paired-pulse ratios. Together, our data suggest that neonatal nicotine exposure alters hippocampal development in sex-dependent manner, resulting in long-lasting changes to synaptic transmission, and potentially contributing to behavioral and cognitive difficulties. |
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| Item Description: | Vita. "Major Subject: Neuroscience". "Submitted to the Office of Research and Graduate Studies of The Texas A&M University System Health Science Center in conjunction with The Texas A&M Institute for Neuroscience in partial fulfillment of the requirements for the degree of Doctor of Philosophy December 2012." Approved as to style and content by: Ursula H. Winzer-Serhan, William H. Griffith, Gerald D. Frye, Mendell J. Rimer, Louise C. Abbott |
| Physical Description: | xii, 178 leaves : illustrations (some color) ; 28 cm. |
| Bibliography: | Includes bibliographical references. |