Recurrent hypoglycemia alters hypothalamic expression of the regulatory proteins FosB and synaptophysin
Date
2008-08-27Author
Al-Noori, Salwa
Sanders, Nicole M.
Taborsky, Gerald J.
Wilkinson, Charles W.
Zavosh, Aryana
West, Connie
Sanders, Colleen M.
Figlewicz, Dianne P.
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Show full item recordAbstract
A limiting factor to the clinical management of diabetes is iatrogenic hypoglycemia. With multiple hypoglycemic
episodes, the collective neuroendocrine response that restores euglycemia is impaired. In our animal model of
recurrent hypoglycemia (RH), neuroendocrine deficits are accompanied by a decrease in medial hypothalamic
activation. Here we tested the hypothesis that the medial hypothalamus may exhibit unique changes in the
expression of regulatory proteins in response to RH. We report that expression of the immediate early gene FosB is
increased in medial hypothalamic nuclei, anterior hypothalamus, and posterior paraventricular nucleus of the
thalamus (THPVN) of the thalamus following RH. We identified the hypothalamic PVN, a key autonomic output site,
among the regions expressing FosB. To identify the subtype(s) of neuronal populations that express FosB, we
screened candidate neuropeptides of the PVN for coexpression using dual fluorescence immunohistochemistry.
Among the neuropeptides analyzed [including oxytocin, vasopressin, thyrotropin-releasing hormone, and corticotropinreleasing
factor (CRF)], FosB was only identified in CRF-positive neurons. Inhibitory !-aminobutyric acid-positive
processes appear to impinge on these FosB-expressing neurons. Finally, we observed a significant decrease in the
presynaptic marker synaptophysin within the PVN of RH-treated vs. saline-treated rats, suggesting that rapid
alterations of synaptic morphology may occur in association with RH. Collectively, these data suggest that RH stress
triggers cellular changes that support synaptic plasticity, in specific neuroanatomical sites, which may contribute to
the development of hypoglycemia-associated autonomic failure.
Keywords: FosB, recurrent hypoglycemia, paraventricular nucleus, corticotropin-