My past research experience has principally been study of the basic morphology of immunocytochemically defined systems, including determination of neurotransmitter content, of primary afferent neurons. Current and future research focuses are alterations of neurotransmitter/neuropeptide content and synaptic rearrangements induced by clinically relevant states. The proposed study is designed to test inducible alterations of putative neurotransmitter content in primary afferent neurons and in particular, in gene-related, peptide (CGRP) afferents which have been implicated in """"""""pain"""""""" transmission. Two physiological conditions have recently been shown in this laboratory to induce alterations in CGRP content in the primary afferent neuron terminals in laminae I and II of the rat spinal cord: (1) a dietary regimen altering serum calcium levels and (2) the spontaneously hypertensive rat which is a model autonomic dysfunction. In the dietary model, low dietary calcium induces a reduction of CGRP in laminae I and II in young rats while high calcium in the diet increases levels of stainable CGRP in the dorsal horn of both young and adult rats. In the hypertensive model, stainable CGRP levels in the dorsal horn are also lower than controls. The present studies will determine if dietary calcium status modulates the neuronal expression of CGRP in spinal cord and brainstem regions involved in autonomic regulation. Are these changes specific for CGRP or is the neuronal content of other peptides altered? Are these changes specific for levels of the spinal cord involved in autonomic regulation or are changes seen at other spinal cord levels and/or the brainstem? Is alteration of CGRP content by dietary calcium a more general phenomenon seen in all CGRP neurons? To characterize the morphological changes seen following dietary calcium alterations, examination of neuronal endings at the electron microscopic level will determine if there are ultrastructural changes indicative of increased CGRP metabolism or storage. Are changes in CGRP content reflected in a dorsal root assay as a relative increase in the percentage of axons stained? To determine if dietary calcium specifically modulates regulation of the expression of CGRP in primary afferent neurons, mRNA levels will be compared to normals in the dietary calcium model and the alteration in CGRP content has important implications in sensory perception which may in turn alter autonomic responses. Increased dietary calcium has been shown to lower blood pressure in spontaneously hypertensive rats, indicating that increased knowledge of the mechanisms under study could have direct clinical applications.
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