Long termgoals of this research seek tounderstand the morphological and functional substrates of the uterine innervation, the response of uterine nerves to steroid sex hormones and how these may play a role in such conditions as preterm labor, protracted labor, autonomic dysreflexia and pregnancy-induced hypertension. The current proposal investigates the autonomic and sensory neural substrate for integration of uterine information and relates these substrates to the altered physical & steroid hormone environment of pregnancy and parturition. Distinct subpopulations of autonomic and sensory neurons innervate the uterus. This specificity of neural organization led to the hypothesis: first, that uterine neurons in autonomic and sensory ganglia provide part of the substrate, which involves estrogen-receptive neurons, to integrate uterine information and secondly, that this substrate plays a role in pregnancy, parturition and viscerovisceral 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.
Specific aims will: 1) characterize sympathetic and vagal inputs to the uterus and determine if autonomic and sensory ganglionic uterine-related neurons contain estrogen receptors (ER), 2) determine if the content and distribution of ER or ER-containing, uterine-related autonomic and sensory neurons change with the altering hormonal milieu of pregnancy & parturition, 3) characterize neurotransmitters of ER-containing neurons in autonomic and sensory ganglia, 4) evaluate whether the input activity to autonomic uterine-related neurons increases during pregnancy and parturition and 5) determine whether some uterine-related neurons influence the cervical ripening of parturition through release of transmitters that act in neurogenic inflammation. These studies will utilize retrograde tracing, in situ hybridization histochemistry, immunohistochemistry, nerve transections, parturition-induced activation of ganglionic neurons, and radioligand binding for ER. Health benefits from understanding involvement of neural mechanisms in the uterus include an increased basic understanding of neuroendocrine coordination of gestational events including pregnancy and parturition and the possibility of remediating problems such as preterm labor, protracted labor, autonomic dysreflexia and pregnancy-induced hypertension.
|Ghosh, Chaitali; Storey-Workley, Megan; Usip, Sharon et al. (2007) Glutamate and metabotropic glutamate receptors associated with innervation of the uterine cervix during pregnancy: receptor antagonism inhibits c-Fos expression in rat lumbosacral spinal cord at parturition. J Neurosci Res 85:1318-35|
|Papka, R E; Workley, M; Usip, S et al. (2006) Expression of pituitary adenylate cyclase activating peptide in the uterine cervix, lumbosacral dorsal root ganglia and spinal cord of rats during pregnancy. Peptides 27:743-52|
|Puder, B A; Papka, R E (2005) Activation and circuitry of uterine-cervix-related neurons in the lumbosacral dorsal root ganglia and spinal cord at parturition. J Neurosci Res 82:875-89|
|Berkley, Karen J; Rapkin, Andrea J; Papka, Raymond E (2005) The pains of endometriosis. Science 308:1587-9|
|Mowa, C N; Papka, R E (2004) The role of sensory neurons in cervical ripening: effects of estrogen and neuropeptides. J Histochem Cytochem 52:1249-58|
|Berkley, Karen J; Dmitrieva, Natalia; Curtis, Kathleen S et al. (2004) Innervation of ectopic endometrium in a rat model of endometriosis. Proc Natl Acad Sci U S A 101:11094-8|
|Mowa, C N; Jesmin, S; Sakuma, I et al. (2004) Characterization of vascular endothelial growth factor (VEGF) in the uterine cervix over pregnancy: effects of denervation and implications for cervical ripening. J Histochem Cytochem 52:1665-74|
|Papka, R E; Mowa, C N (2003) Estrogen receptors in the spinal cord, sensory ganglia, and pelvic autonomic ganglia. Int Rev Cytol 231:91-127|
|Mowa, C N; Usip, S; Storey-Workley, M et al. (2003) Substance P in the uterine cervix, dorsal root ganglia and spinal cord during pregnancy and the effect of estrogen on SP synthesis. Peptides 24:761-71|
|Mowa, C N; Usip, S; Collins, J et al. (2003) The effects of pregnancy and estrogen on the expression of calcitonin gene-related peptide (CGRP) in the uterine cervix, dorsal root ganglia and spinal cord. Peptides 24:1163-74|
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