Neurotransmitters, neuropeptides and binding sites in the rat mediobasal hypothalamus: effects of monosodium glutamate (MSG) lesions

Abstract

Indirect immunofluorescence histochemistry and receptor autoradiography were used to study the localization of transmitter-/peptide-containing neurons and peptide binding sites in the mediobasal hypothalamus in normal rats and in rats treated neonatally with repeated doses of the neurotoxin monosodium-glutamate (MSG). In the arcuate nucleus, the results showed a virtually complete loss of cell bodies containing immunoreactivity for growth hormone-releasing factor (GRF), galanin (GAL), dynorphin (DYN), enkephalin (ENK), corticotropin-like intermediate peptide (CLIP), neuropeptide Y (NPY), and neuropeptide K (NPK). Tyrosine hydroxylase(TH)-glutamic acid decarboxylase(GAD)-, neurotensin(NT)- and somatostatin(SOM)-immunoreactive (IR) cells were, however, always detected in the ventrally dislocated, dorsomedial division of the arcuate nucleus. In the median eminence, marked decreases in numbers of GAD-, NT-, GAL-, GRF-, DYN-, and ENK-IR fibers were observed. The numbers of TH-, SOM- and NPY-IR fibers were in contrast not or only affected to a very small extent, as revealed with the immunofluorescence technique. Biochemical analysis showed a tendency for MSG to reduce dopamine levels in the median eminence of female rats, whereas no effect was observed in male rats. Autoradiographic studies showed high to moderate NT binding sites, including strong binding over presumably dorsomedial dopamine cells. In MSG-treated rats, there was a marked reduction in GAL binding in the ventromedial nucleus. The findings implicate that most neurons in the ventrolateral and ventromedial arcuate nucleus are sensitive to the toxic effects of MSG, whereas a subpopulation of cells in the dorsomedial division of the arcuate nucleus, including dopamine neurons, are not susceptible to MSG-neurotoxicity. The results indicate, moreover that the very dense TH-IR fiber network in the median eminence predominantly arises from the dorsomedial TH-IR arcuate cells, whereas the GAD-, NT-, GAL-, GRF- and DYN-IR fibers in the median eminence to a large extent arise from the ventrolateral arcuate nucleus. Some ENK- and NPK-positive cells in the arcuate nucleus seem to project to the lateral palisade zone of the median eminence, but most of the ENK-IR fibers in the median eminence, located in the medial palisade zone, seem to primarily originate from an area(s) located outside the arcuate nucleus, presumably the paraventricular nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Regulation of Neurotransmission in the Arcuate Nucleus of the Rat by Different Neuropeptide Y Receptors

“…Not only is the arcuate nucleus the source of much of the NPY containing innervation of the PVN, but these neurons also send collaterals back into the arcuate, thereby contributing significantly to the NPY innervation of the arcuate itself (Meister et al, 1989). Regulation of the activity of these neurons may be an important way of regulating food intake.…”

“…It is believed that NPY-containing neurons, which project from the arcuate nucleus to the paraventricular nucleus and also send collaterals back into the arcuate, may normally play an important role in the control of feeding behavior and in neuroendocrine regulation (Meister et al, 1989;Erickson et al, 1996a,b;Kalra and Kalra, 1996;Miller and Bell, 1996). These neurons may participate in a negative feedback "lipostat" arrangement whereby they are inhibited by leptin, a cytokine secreted from adipose tissue that inhibits food intake (Stephens et al, 1995;Erickson et al, 1996a,b;Glaum et al, 1996;Miller and Bell, 1996).…”

The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice

“…If so, AGRP staining could be used to map the terminal projections of arcuate NPY neurons. To further ascertain the arcuate origin of AGRPimmunoreactive (ir) terminals, we also analyzed mice treated neonatally with monosodium glutamate (MSG), which induces necrosis of arcuate neurons (18), including the NPY cells (11,19). In addition, we studied AGRP in the mutant anorexia (anx͞anx) mouse, where abnormalities in arcuate NPY histochemistry have been demonstrated (9).…”

“…In genetic models of feeding disorders, arcuate NPY overexpression has been linked to hyperphagia and obesity (8), and NPY deficiency has been linked to hypophagia and anorexia (9). However, surprisingly little information is available on the arcuate NPY projections, and targets for these neurons so far have been demonstrated only in a limited number of hypothalamic nuclei (10)(11)(12). Recently, Hahn et al (13) and we (14) have reported that many NPY neurons in the rodent arcuate coexpress agouti gene-related protein (AGRP) (15), an endogenous antagonist of the anorexigenic melanocortin peptides, e.g., ␣-melanocytestimulating hormone (␣MSH) (16,17).…”

Effects of hindbrain melanin-concentrating hormone and neuropeptide Y administration on licking for water, saccharin, and sucrose solutions.

“…36, 68). For example, hypothalamic NPY systems are not essential for the mediation of exogenous NPY-induced feeding, as NPY-related lesions of the ARC, paraventricular nucleus, or basal hypothalamus fail to prevent either hyperphagic responses to ICV NPY (2,17,52,54) or the attainment of normal levels of food intake, body weight, and adiposity in adulthood (13,38).…”