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

Kimberly M. Pelz, David Routman, Joseph R. Driscoll, Lance J. Kriegsfeld, John Dark
2008 American Journal of Physiology. Regulatory Integrative and Comparative Physiology  
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. 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
more » ... ves 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 2DGinduced 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 decrease by as much as ϳ20°C for 5-8 h (27, 43). Siberian hamsters expressing torpor typically do so 2-3 times a week (43). Expression of daily torpor generates a significant savings in energy expenditure, thus decreasing energy intake requirements in winter (21, 41). Although most photoperiodic responses (e.g., reduced food intake and reproductive regression) are initiated within several weeks of the onset of a winterlike photoperiod, torpor is not initiated for ϳ12 wk (e.g., Ref. 23). This time coincides with the nadir in body mass (4, 6, 42) and minimal white adipose tissue reserves (5). Reduced fat reserves appear necessary for photoperiod-dependent daily torpor because high leptin concentrations suppress torpor expression (19, 20, 22) . Only Siberian hamsters with markedly reduced serum leptin concentrations (Ͻ2.6 ng/ml) enter torpor, suggesting that chronically low leptin concentrations are a permissive factor for torpor onset (19) . Reduced leptin concentrations are required for the exaggerated circadian decrease in T b during daily torpor, and ob/ob mice, which are leptin deficient, undergo a significantly greater decrease in circadian T b min than do lean mice. Even though food restriction decreases T b min in both lean and ob/ob mice, it is reduced to a greater degree in ob/ob mice (28). Exogenous leptin treatment, on the other hand, prevents food restriction from decreasing T b min in lean mice (14). Suckling-age rat pups undergo similar decreases in light/rest phase T b and metabolic rate. This decrease is due to a temporary shutdown of sympathetic mediated nonshivering thermogenesis in brown adipose tissue (BAT) (33, 38) and, as in adult animals, is blocked by leptin treatments (48). Repeated postnatal monosodium glutamate (MSG) treatments produce a specific pattern of neural degeneration primarily focused in the hypothalamic arcuate nucleus (ARC) (e.g., Refs. 7 and 26), especially targeting ARC neuropeptide Y and proopiomelanocortin neurons, which both colocalize leptin receptors but have opposing effects on metabolism (9, 26, 31). MSG ablation of the ARC eliminates "torpor-like" circadian decreases in T b in suckling rats (45). The purpose of the present series of studies was to determine whether MSG-induced ablation of ARC mechanisms would eliminate photoperiod-dependent torpor, whose onset appears dependent upon chronically reduced leptin feedback as a permissive factor. ARC MSG lesions have been successfully produced in Siberian hamsters, demonstrating that SP-induced changes in hamster body mass, food intake, fur color, and testis mass persist after ARC ablation (16). If MSG ablations in Siberian hamsters mimic the effect on circadian T b min in suckling rat pups (45) , then ARC MSG ablations should eliminate photoperiod-dependent torpor in hamsters. Differ-Address for reprint requests and other correspondence: J. Dark, Psychology
doi:10.1152/ajpregu.00387.2007 pmid:17959707 fatcat:oq7gucjv4bbzja3nqx2d4udiem