This research seeks new information about the regenerative and sprouting capabilities of central and peripheral peptidergic pathways, and about the microenvironments in which these responses occur. Two autonomic models will be used; the central amygdaloid nucleus (CNA) and the superior cervical ganglion (SCG). The CNA studies will exploit its rich content of peptidergic terminals, as well as its fortuitous arrangement of two principal inputs which provide a means for deafferentation experiments. Lesioning a major input (and output) pathway of the CNA revealed increased, and maintained, somatostatin (SS) immunoreactivity; whereas the neurotensin (NT) immunoreactivity was initially reduced but later restored. Computer-assisted image analysis will be used to study light microscopic preparations a) in the normal b) after lesion-induced degeneration and c) during reorganization evoked by the lesions. This leads to an ultrastructural immunocytochemical evaluation of the events associated with hypothesized SS and NT sprouting, including the possibility that some changes in peptidergic elements (e.g. in profiles of axon terminals) may be due to lesion-induced release from transneuronal regulation. Radio-immunoassays will be used to confirm and quantify changed SS and NT levels after various post-lesion intervals. In subsequent experiments, a retrograde fluorescent tracer (SITS) combined with an immunohistochemical method will be used to identify origins of peptidergic pathways to the CNA, and therefore the possible extrinsic sources for the sprouts. In a companion study, research with the SCG is aimed at providing an understanding of its synaptic reorganization following a preganglionic freeze lesion. At the ultrastructural level, chemically identifiable synapses between various components will be classified and quantified. In addition, the regenerative capabilities of enkephalin-positive and enkephalin-negative axons will be evaluated. It is hoped that this work will take us along the road toward identifying the factors involved in synaptic mobility of peptidergic neurons. It is hypothesized that neuropeptides are involved in production of some disorders accompanied by a decline in neural reserve. This reaches the threshold of clinical deficit in some dementias, 60% to 70% of dementia being due to Alzheimer's disease, which affects 5% to 10% of people over 65 years of age and 30% of people over 80 years.
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