Expression of nicotinic acetylcholine receptors and the effects of neonatal nicotinic exposure on GABAergic interneurons in rat hippocampus : a dissertation /
| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
[College Station, Tex.] :
[Texas A&M University System Health Science Center],
[2009]
|
| Subjects: |
| Abstract: | ABSTRACT: Nicotine, the major psychoactive ingredient in tobacco, activates neuronal nicotinic acetylcoline receptors (nAChRs). These, pentameric cation channels, are also expressed in the developing brain including the hippocampus, a structure involved in cognitive functions. GABAergic interneurons a very diverse neuronal population, are widely distributed in adult and developing hippocampus, forming synapses onto excitory and inhibitory neurons, thereby regulating synaptic and circuitry activity. Functional studies have shown activation of nAChRs on interneurons and nicotine-stimulated GABA release in adult and postnatal hippocampus. Therefore, we first examined the anatomical expression of nAChR subunits in GABAergic interneurons using double in situ hybridization to identify possible nAChR subtypes. The results revealed that [alpha]7 and [beta]2 subunits are predominantly expressed in interneurons, wheras other [alpha] subunits exhibited limited expression. This suggests that the major subtype in the [alpha]7 homomeric receptor, but hereomeric nAChRs could be expressed in spatially restricted neuronal populations. A population of GABAegic pioneer neurons is found in the neonatal hippocampus, which decreases in number postnatally. Activation of nAChRs by nicotine has been shown to reduce cell death. Thus, chronic neonatal nicotine (CNN) exposure could increase numbers of mature interneurons by interfering with apooptosis of pioneer neurons. Therefore, we determined the numbers of GABAergic interneurons in adult males exposed to CNN, using a variety of different approaches and neuronal markers for GABAergic interneurons, and the effect was more pronounced in subgroups of GABAergic neurons particularly in CA1/3 stratum oriens such as basket-/chandelier- and O-LM (oriens-lacunosum moleculare) neurons. Finally, the expression of growth factors was studied as a possible mechanism for the anti-apoptotic effects of CNN. The results showed that CNN exposure increased the expression of growth factor mRNAs for BDNF, FGF-2, NT-3, and IGF-1, but not NGF in the developing hippocampus. Taken together, nAChR subunits are expressed in hippocampus in adults and during development. CNN exposure appears to reduce developmentally regulated cell death of pioneer GAD67 interneurons, possibly by upregulation of growth factor expression. This results in increased numbers of interneurons, which could elevate GABAergic inhibitory tone and could contribute to altered hippocampal function. These findings could possibly explain the long-term consequences on cognitive function in the offspring of mothers who smoked during pregnancy. |
|---|---|
| Item Description: | Vita. "Major Subject: Medical Sciences". "Submitted to the Office of Research and Graduate Studies of The Texas A&M University System Health Science Center in partial fulfillment for the requirements for the degree of Doctor of Philosophy May 2009." Approved as to style and content by: Ursula H. Winzer-Serhan, Gerald D. Frye, Louise C. Abbott, William H. Griffith. |
| Physical Description: | xvi, 162 leaves : illustrations ; 28 cm. |
| Bibliography: | Includes bibliographical references (leaves 140-159). |