The long-term goal of this research is to understand spinal cord and other CNS mechanisms for integration of uterine information and how these play a role in such pathologic conditions as autonomic dysreflexia and pregnancy-induced hypertension. The current proposal is designed to reveal spinal cord mechanisms for integration of uterine information and how these mechanisms relate to the altered physical and steroid hormone environment of pregnancy and parturition and the changing steroid hormone environment of the estrous cycle. Distinct subpopulations of spinal neurons innervate different pelvic organs (e.g., bladder versus colon). This specificity of neural organization led to the hypothesis: uterine-related neurons in the lumbosacral spinal cord provide the central mechanisms to integrate uterine information, these mechanisms involve estrogen-receptive neurons and process uterine information important in pregnancy and parturition and neuroendocrine reflexes. A specific role for estrogen in these pathways is hypothesized because estrogen modulates neurochemical systems in the CNS and influences sensitivity of primary afferent nerves. Consequently, the proposed studies are designed to address five specific aims: 1) determine if there are uterine-related neurons in the lumbosacral spinal cord, brainstem and hypothalamus and determine if these neurons have a special topography, 2) determine if there are estrogen receptor(ER)-containing neurons in the lumbosacral cord and brainstem, if uterine-related neurons contain ER, and if these neurons are altered with the changing hormonal milieu during pregnancy and parturition and during the estrous cycle, 3) identify neurotransmitters of intrinsic and descending projection inputs to uterine-related neurons and determine if their patterns are altered with the changing hormonal milieu during pregnancy and parturition and during the estrous cycle, 4) evaluate neurotransmitters of primary afferent input to uterine-related neurons and determine if their patterns are altered with the changing hormonal milieu during pregnancy and parturition and during the estrous cycle, and 5) determine if uterine-related lumbosacral spinal neurons respond to stimulation of uterine afferents, if some of these project to the hypothalamus and contain ERs. These studies will utilize transneuronal tract-tracing combined with immunohistochemistry, mechanical stimulus- induced activation of uterine-related spinal neurons and retrograde tracing. Animals used in these studies include pregnant and parturient rats, cycling rats and hormonally-manipulated rats. Health benefits will be derived from the results of this proposal. This information will increase our understanding of involvement of neural mechanisms in human pregnancy and parturition, hormonal influences on these central mechanisms and how the central mechanisms and pathways relate to neural- endocrine coordination of gestational events and such problems as preterm labor, pathologic conditions such as autonomic dysreflexia associated with spinal cord injury and pregnancy-induced hypertension.
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