neuropeptide-y and homocysteic-acid

The role of the paraventricular nucleus of the hypothalamus (PVN) in the regulation of energy expenditure and energy substrate utilization was investigated after the injection of the excitatory amino acid D,L-homocysteic acid (DLH) or its vehicle. Male Wistar rats with chronic PVN cannulae were tested for 1 h with no food available in an open-circuit calorimeter. Whereas low (0.5 nmol), excitatory doses of DLH increased energy expenditure, the thermogenic effect became smaller and then vanished as the DLH dose was increased to inhibitory levels (7 and 50 nmol). None of these doses affected motor activity, indicating a primary thermogenic effect. The highest dose (100 nmol) increased energy expenditure, but this appeared to be secondary to increased locomotor activity. The increased locomotor activity produced by the highest dose of DLH constitutes the first demonstration of an activity effect induced by stimulating the PVN. However, this effect likely reflects the activation of neighboring areas. Only the 50 nmol dose of DLH increased respiratory quotient, indicating a shift toward the preferential utilization of carbohydrates as an energy substrate. These data complement our findings with neuropeptide Y and insulin in showing that different doses of the same substance injected into the PVN may produce qualitatively different effects. Furthermore, the present study demonstrates that exciting PVN neurons activates catabolic forces, whereas inhibiting them activates anabolic forces.

Topics: Amino Acids; Animals; Body Temperature; Energy Metabolism; Homocysteine; Insulin; Male; Motor Activity; Neuropeptide Y; Oxygen Consumption; Paraventricular Hypothalamic Nucleus; Rats; Rats, Wistar; Respiratory Mechanics

L-Homocysteic acid (L-HCA) is a sulfated amino acid which is present in mammalian striatum and is a putative excitatory striatal neurotransmitter. In the present study we examined the histologic and neurochemical effects of L-HCA induced striatal lesions to determine how closely changes resemble those of Huntington's disease (HD). Increasing doses of L-HCA injected into the anterior striatum resulted in dose-dependent reductions in both substance P-like immunoreactivity (SP-LI) and gamma-aminobutyric acid (GABA) while there was a relative sparing of both somatostatin-like immunoreactivity (SS-LI) and neuropeptide Y-like immunoreactivity (NPY-LI). Immunocytochemical studies showed a relative sparing of NADPH-diaphorase neurons (which colocalize with SS and NPY) within regions in which there was a significant depletion of enkephalin stained neurons. The lesions were blocked by pretreatment with MK-801, a systemically effective non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors or coinjection of equimolar concentrations of 2-amino-5-phosphonovalerate (APV). These findings are similar to those produced with the NMDA agonist quinolinic acid, and suggest that other endogenous NMDA agonists, such as L-HCA, could be potential excitotoxins in HD.

Topics: 2-Amino-5-phosphonovalerate; Animals; Corpus Striatum; Dibenzocycloheptenes; Dizocilpine Maleate; Dose-Response Relationship, Drug; gamma-Aminobutyric Acid; Homocysteine; Immunohistochemistry; Male; Neuropeptide Y; Rats; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter; Somatostatin; Substance P