Quantitative autoradiographic characterization of GABA(B) receptors in mammalian central nervous system.
dc.contributor.author | Chu, Dorothy Chin-Mei | |
dc.contributor.advisor | Young, Anne B. | |
dc.contributor.advisor | Penney, John B. | |
dc.date.accessioned | 2016-08-30T16:46:58Z | |
dc.date.available | 2016-08-30T16:46:58Z | |
dc.date.issued | 1989 | |
dc.identifier.uri | http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:8920511 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/128313 | |
dc.description.abstract | The inhibitory effects of the amino acid neurotransmitter $\gamma$-aminobutyric acid (GABA) within the nervous system appear to be mediated through two distinct classes of receptors: GABA$\sb{\rm A}$ and GABA$\sb{\rm B}$ receptors. A quantitative autoradiographic method with $\sp3$H-GABA was developed to examine the hypotheses that GABA$\sb{\rm A}$ and GABA$\sb{\rm B}$ sites have distinct anatomical distributions, pharmacologic properties, and synaptic localizations within the rodent nervous system. The method was also applied to a comparative study of these receptors in postmortem human brain from individuals afflicted with Alzheimer's disease and those without neurologic disease. The results indicated that GABA$\sb{\rm B}$ receptors occur in fewer numbers and have a lower affinity for GABA than GABA$\sb{\rm A}$ receptors in both rodent and human brain. Within rodent brain, the distribution of these two receptor populations were clearly distinct. GABA$\sb{\rm B}$ receptors were enriched in the medial habenula, interpeduncular nucleus, cerebellar molecular layer and olfactory glomerular layer. After selective lesions of postsynaptic neurons of the corticostriatal and perforant pathway, both GABA$\sb{\rm B}$ and GABA$\sb{\rm A}$ receptors were significantly decreased in number. Lesions of the presynaptic limbs of the perforant but not the corticostriatal pathway resulted in upregulation of both GABA receptors in the area of innervation. GABA$\sb{\rm B}$ receptors were also upregulated in CA3 dendritic regions after destruction of dentate granule neurons. These findings were consistent with a postsynaptic localization of GABA$\sb{\rm B}$ receptors and were suggestive of feed-forward inhibitory circuits in the perforant and mossy fiber pathways. Numbers of GABA$\sb{\rm B}$ receptors were reduced by as much as 70% in hippocampus and frontal cortex in persons with Alzheimer's disease as compared to controls. The distribution of GABA receptor losses paralleled the distinct pattern of nerve cell atrophy associated with this neurodegenerative disorder. | |
dc.format.extent | 271 p. | |
dc.language | English | |
dc.language.iso | EN | |
dc.subject | Autoradiographic | |
dc.subject | Central | |
dc.subject | Characterization | |
dc.subject | Gaba(b) | |
dc.subject | Mammalian | |
dc.subject | Nervous | |
dc.subject | Quantitative | |
dc.subject | Receptors | |
dc.subject | System | |
dc.title | Quantitative autoradiographic characterization of GABA(B) receptors in mammalian central nervous system. | |
dc.type | Thesis | |
dc.description.thesisdegreename | PhD | en_US |
dc.description.thesisdegreediscipline | Biological Sciences | |
dc.description.thesisdegreediscipline | Neurosciences | |
dc.description.thesisdegreegrantor | University of Michigan, Horace H. Rackham School of Graduate Studies | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/128313/2/8920511.pdf | |
dc.owningcollname | Dissertations and Theses (Ph.D. and Master's) |
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