Disruption of neural signaling within the hypothalamic ventromedial nucleus upregulates galanin gene expression in association with hyperphagia: an in situ hybridization analysis.
Hypothalamic neuropeptides play critical roles in the regulation of appetite and body weight. We recently reported that disruption of neural signaling in the ventromedial nucleus (VMN) by microinjection of the neurotoxin, colchicine (COL), produced transient hyperphagia with attendant body weight gain lasting for 4 days. The neural mechanism(s) underlying this temporary shift in energy homeostasis is still unknown. Galanin (GAL) is produced in several hypothalamic nuclei and since microinjection of GAL into these sites stimulates feeding, we tested the hypothesis that galaninergic signaling is upregulated in COL-treated rats. COL (4 microgram in 0.5 microliter saline) or saline alone was microinjected into the VMN of adult male rats and GAL mRNA was evaluated in the basal hypothalamus by ribonuclease protection assay on day 1, day 2 and day 4 after injection. Whereas in saline-treated rats body weight and GAL mRNA remained unaffected, they were significantly increased in COL-injected rats through the period of observation. To identify the specific neuronal subpopulations involved, GAL mRNA levels were analyzed in feeding-related hypothalamic nuclei using semiquantitative in situ hybridization histochemistry on day 4 after microinjection of COL or saline into the VMN. In COL-treated rats, GAL mRNA levels increased dramatically over controls in the supraoptic nucleus, paraventricular nucleus (PVN), dorsomedial nucleus (DMN), arcuate nucleus (ARC) and lateral hypothalamic area (LHA); no significant change was observed in the central nucleus of amygdala. These results indicated that disruption of neurotransmission in the VMN upregulated GAL gene expression in those hypothalamic sites (PVN, DMN, LHA and ARC) that are implicated in regulation of feeding, and since GAL stimulates feeding, this neurochemical rearrangement may contribute to the over-eating in these animals. These results also suggest that, normally, neurons in the VMN may suppress GAL neurotransmission in feeding-regulating hypothalamic neural circuits.
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Department of Neuroscience, University of Florida College of Medicine, University of Florida Brain Institute, PO Box 100244, Gainesville, FL 32610, USA. pu@neocortex.health.ufl.edu
Dube
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Edwards
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Kalra
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Kalra
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D000818:Animals; D003078:Colchicine / Q000494:pharmacology; D005247:Feeding Behavior / Q000502:physiology; D019004:Galanin / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006963:Hyperphagia / Q000503:physiopathology*; D017403:In Situ Hybridization; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000737:chemistry / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014697:Ventromedial Hypothalamic Nucleus / Q000737:chemistry / Q000166:cytology / Q000502:physiology*
D012333:RNA, Messenger; D019004:Galanin; D003078:Colchicine