Monosodium glutamate-induced arcuate nucleus damage affects both natural torpor and 2DG-induced torpor-like hypothermia in Siberian hamsters

Abstract

Pelz KM, Routman D, Driscoll JR, Kriegsfeld LJ, Dark J. Monosodium glutamate-induced arcuate nucleus damage affects both natural torpor and 2DG-induced torpor-like hypothermia in Siberian hamsters. Am J Physiol Regul Integr Comp Physiol 294: R255-R265, 2008. First published March 1, 2007 doi:10.1152/ajpregu.00387.2007.-Siberian hamsters (Phodopus sungorus) have the ability to express daily torpor and decrease their body temperature to ϳ15°C, providing a significant savings in energy expenditure. Daily torpor in hamsters is cued by winterlike photoperiods and occurs coincident with the annual nadirs in body fat reserves and chronic leptin concentrations. To better understand the neural mechanisms underlying torpor, Siberian hamster pups were postnatally treated with saline or MSG to ablate arcuate nucleus neurons that likely possess leptin receptors. Body temperature was studied telemetrically in cold-acclimated (10°C) male and female hamsters moved to a winterlike photoperiod (10:14-h light-dark cycle) (experiments 1 and 2) or that remained in a summerlike photoperiod (14:10-h light-dark cycle) (experiment 3). In experiment 1, even though other photoperiodic responses persisted, MSG-induced arcuate nucleus ablations prevented the photoperioddependent torpor observed in saline-treated Siberian hamsters. MSGtreated hamsters tended to possess greater fat reserves. To determine whether reductions in body fat would increase frequency of photoperiod-induced torpor after MSG treatment, hamsters underwent 2 wk of food restriction (70% of ad libitum) in experiment 2. Although food restriction did increase the frequency of torpor in both MSG-and saline-treated hamsters, it failed to normalize the proportion of MSGtreated hamsters undergoing photoperiod-dependent torpor. In experiment 3, postnatal MSG treatments reduced the proportion of hamsters entering 2DG-induced torpor-like hypothermia by ϳ50% compared with saline-treated hamsters (38 vs. 72%). In those MSG-treated hamsters that did become hypothermic, their minimum temperature during hypothermia was significantly greater than comparable salinetreated hamsters. We conclude that 1) arcuate nucleus mechanisms mediate photoperiod-induced torpor, 2) food-restriction-induced torpor may also be reduced by MSG treatments, and 3) arcuate nucleus neurons make an important, albeit partial, contribution to 2DG-induced torpor-like hypothermia. thermoregulation; leptin; neuropeptide Y; body mass; fat SIBERIAN HAMSTERS UNDERGO numerous physiological and behavioral changes when experiencing a winterlike photoperiod with a short photophase (SP) and low ambient temperatures (T a ), including bouts of shallow, daily torpor (e.g., Ref. 23). Daily torpor is a form of reversible hypothermia that occurs during the rest/sleep phase of the circadian cycle, coincident with the time of the circadian minimum in body temperature (T b ). In fact, it is accepted that this represents an exaggeration of the usual 1-3°C sleep-dependent decrease in T b (13, 52). During daily torpor, however, T b may ...

Regulation of Peripheral Metabolism by Substrate Partitioning in the Brain

“…Increased peripheral glucose metabolism from VMH stimulation does not entail increased glucose transporters, in contrast to insulin-induced glucose uptake [38]. Associated with increased glucose metabolism, VMH stimulation also increases BAT temperature [39], likely reflecting hypothalamic mediation of hypothermia induced by 2DG [40]. Infusion of leptin specifically into the VMH also induces peripheral glucose metabolism [41] through enhancement of sympathetic nervous activity [42].…”

The regulation of food intake in mammalian hibernators: a review

“…In photoperiodic hibernators (hamsters), there is evidence that the ARC is involved in mediating torpor, and that changes in nutrients within the ARC may be involved in the response (Pelz et al 2008). Using monosodium glutamate (MSG) to induce ARC neuronal damage, Pelz et al (2008) showed that MSG-treated animals did not enter torpor as frequently as controls under a short photoperiod.…”

“…Using monosodium glutamate (MSG) to induce ARC neuronal damage, Pelz et al (2008) showed that MSG-treated animals did not enter torpor as frequently as controls under a short photoperiod. Furthermore, food restriction-induced torpor was also reduced in MSG-treated animals.…”

Neural Signaling Metabolites May Modulate Energy Use in Hibernation

“…26 Ablation of the arcuate nucleus abolishes torpor in Siberian hamsters and fasting-induced torpor in mice. 27 Ghrelin, a gut appetite hormone and neuropeptide activates NPY neurons in the arcuate nucleus and deepens torpor in mice. 28 These studies support the hypothesis that NPY Y1 receptor sites activated by NPY within the arcuate nucleus induce a torpor-like state through modulation of thermoregulation.…”

“…28 These studies support the hypothesis that NPY Y1 receptor sites activated by NPY within the arcuate nucleus induce a torpor-like state through modulation of thermoregulation. 26, 27, 29 The efficacious orexigenic effect of NPY, however, is difficult to reconcile within the context of hibernation because onset of hibernation is preceded by a hypophagic period. 30 Indeed, TRH is the only member of the group of neuropeptides, well-known to regulate food intake that is upregulated in the hypothalamus during pre-hibernation satiety 30 .…”