Colocalization of tyrosine hydroxylase and Fos in the male Syrian hamster brain following different states of arousal

In an investigation of the role that central tyrosine hydroxylase-(TH) containing neurons play in copulation in the male Syrian hamster, The induction of Fos protein was used as an index of neuronal activation. With a double immunoperoxidase technique, the activation of TH neurons was compared in hamsters from three experimental groups: (1) mated in a new cage; (2) handled controls placed in a new cage, and (3) unhandled controls. Although mating selectively induces Fos production in the medial amygdaloid nucleus (Me), more than half of the TH neurons in Me (a region outside of the classical catecholamine systems) expressed Fos equally in all of the experimental groups. In the paraventricular hypothalamic nucleus (PVN), TH neurons were activated equivalently in mated and handled control animals compared to unhandled controls. TH neurons in the neucleus of the solitary tract (NST) were also activated in handled control animals, and mating further enhanced the level of Fos immunostaining in these neurons above both groups of nonmated animals. Although not quantified, co-localization of Fos and TH was also observed in all experimental groups in the olfactory bulbs and the interfascicular nucleus, and in the horizontal limb of the diagonal band of Broca and the cerebral cortex, regions which contain TH neurons but are not part of the classically described TH cell groups. Few, if any, TH neurons in other catecholaminergic brain regions, such as the substantia nigra and locus coeruleus, produced Fos in any of the experimental groups. These results suggest that TH neurons in the PVN and NST may be activated during different states of arousal, and that nonclassical TH neurons in the amygdala produce high levels of Fos even in unstimulated animals. 1994 John Wiley & Sons, Inc.     

Corticotrophin-releasing factor mediates hypophagia after adrenalectomy, increasing meal-related satiety responses

Adrenalectomy-induced hypophagia is associated with increased satiety-related responses, which involve neuronal activation of the nucleus of the solitary tract (NTS). Besides its effects on the pituitary–adrenal axis, corticotrophin-releasing factor (CRF) has been shown to play an important role in feeding behaviour, as it possesses anorexigenic effects. We evaluated feeding-induced CRF mRNA expression in the paraventricular nucleus (PVN) and the effects of pretreatment with CRF₂ receptor antagonist (Antisauvagine-30, AS30) on food intake and activation of NTS neurons in response to feeding in adrenalectomised (ADX) rats. Compared to the sham group, ADX increased CRF mRNA levels in the PVN of fasted animals, which was further augmented by refeeding. AS30 treatment did not affect food intake in the sham and ADX + corticosterone (B) groups; however, it reversed hypophagia in the ADX group. In vehicle-pretreated animals, refeeding increased the number of Fos and Fos/TH-immunoreactive neurons in the NTS in the sham, ADX and ADX + B groups, with the highest number of neurons in the ADX animals. Similarly to its effect on food intake, pretreatment with AS30 in the ADX group also reversed the increased activation of NTS neurons induced by refeeding while having no effect in the sham and ADX + B animals. The present results show that adrenalectomy induces an increase in CRF mRNA expression in the PVN potentiated by feeding and that CRF₂ receptor antagonist abolishes the anorexigenic effect and the increased activation of NTS induced by feeding in the ADX animals. These data indicate that increased activity of PVN CRF neurons modulates brainstem satiety-related responses, contributing to hypophagia after adrenalectomy.     

Feeding Induced by Pharmacological Blockade of Fatty Acid Metabolism Is Selectively Attenuated by Hindbrain Injections of the Galanin Receptor Antagonist,M40

Galanin has been shown to stimulate feeding when injected intracranially in rats. Lesion and Fos studies have shown that the neural pathway for feeding stimulated by mercaptoacetate (MA) -induced blockade of fatty acid oxidation includes several structures rich in galanin cell bodies or terminals. In the present experiment, we examined the role of hindbrain galanin in feeding stimulated by MA. We found that galanin (1 nmol) stimulates feeding when injected into the nucleus of the solitary tract (NTS), a site that is crucial for MA-induced feeding, or into the fourth ventricle (4V, 1 or 5 nmol) and that NTS or 4V injections of the galanin receptor antagonist, M40 (1.5 or 5 nmol), completely blocked feeding induced by MA (68 mg/kg). The effect of the M40 appeared to be specific for MA-induced feeding, since M40 did not significantly attenuate either feeding induced by the antimetabolic glucose analog, 2-deoxy-D-glucose (2DG, 100 or 200 mg/kg), or deprivation-induced water intake. Results suggest that feeding induced by decreased fatty acid oxidation relies upon galaniner-gic terminals in the hindbrain. Furthermore, results indicate that hindbrain neurons involved in MA-induced feeding differ neurochemically from those important for 2DG-induced feeding.     

A Vagal-NTS Neural Pathway that Stimulates Feeding

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Hypothalamic lipotoxicity and the metabolic syndrome

Ectopic accumulation of lipids in peripheral tissues, such as pancreatic β cells, liver, heart and skeletal muscle, leads to lipotoxicity, a process that contributes substantially to the pathophysiology of insulin resistance, type 2 diabetes, steatotic liver disease and heart failure. Current evidence has demonstrated that hypothalamic sensing of circulating lipids and modulation of hypothalamic endogenous fatty acid and lipid metabolism are two bona fide mechanisms modulating energy homeostasis at the whole body level. Key enzymes, such as AMP-activated protein kinase (AMPK) and fatty acid synthase (FAS), as well as intermediate metabolites, such as malonyl-CoA and long-chain fatty acids-CoA (LCFAs-CoA), play a major role in this neuronal network, integrating peripheral signals with classical neuropeptide-based mechanisms. However, one key question to be addressed is whether impairment of lipid metabolism and accumulation of specific lipid species in the hypothalamus, leading to lipotoxicity, have deleterious effects on hypothalamic neurons. In this review, we summarize what is known about hypothalamic lipid metabolism with focus on the events associated to lipotoxicity, such as endoplasmic reticulum (ER) stress in the hypothalamus. A better understanding of these molecular mechanisms will help to identify new drug targets for the treatment of obesity and metabolic syndrome.