Changes in brain tissue and behavior patterns induced by single short-term fasting in mice.

In humans, emaciation from long-term dietary deficiencies, such as anorexia, reportedly increases physical activity and brain atrophy. However, the effects of single short-term fasting on brain tissue or behavioral activity patterns remain unclear. To clarify the impact of malnutrition on brain function, we conducted a single short-term fasting study as an anorexia model using male adult mice and determined if changes occurred in migratory behavior as an expression of brain function and in brain tissue structure. Sixteen-week-old C57BL/6J male mice were divided into either the fasted group or the control group. Experiments were conducted in a fixed indoor environment. We examined the effects of fasting on the number of nerve cells, structural changes in the myelin and axon density, and brain atrophy. For behavior observation, the amount of food and water consumed, ingestion time, and the pattern of movement were measured using a time-recording system. The fasted mice showed a significant increase in physical activity and their rhythm of movement was disturbed. Since the brain was in an abnormal state after fasting, mice that were normally active during the night became active regardless of day or night and performed strenuous exercise at a high frequency. The brain weight did not change by a fast, and brain atrophy was not observed. Although no textural change was apparent by fasting, the neuronal neogenesis in the subventricular zone and hippocampus was inhibited, causing disorder of the brain function. A clear association between the suppression of encephalic neuropoiesis and overactivity was not established. However, it is interesting that the results of this study suggest that single short-term fasting has an effect on encephalic neuropoiesis.

Effects of nestin-antisense treatment in mice on memory-related performance.

Nestin is a neuronal stem cell marker. It has been reported that newly generated adult neurons play a role in murine memory. The purpose of this study was to determine whether nestin itself plays a role in memory function in adult animals. Mice were infused intraventricularly with nestin-selective, morpholino-modified antisense oligodeoxynucleotides for 6 days, after which their ability to perform a new memory-related, food-search task was assessed. Such treatment was found to reduce the training effect on food-search test performance. Immunohistochemical staining revealed that nestin-positive cells within the hippocampal dentate gyrus and subventricular zone were attenuated in these animals. These data support a role for nestin in adult memory and learning.

Ghrelin deficiency does not influence feeding performance.

Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor that is synthesized predominantly in the stomach. Previous studies demonstrated that ghrelin stimulates growth hormone release and food intake. These data suggested that antagonism of ghrelin could serve as a useful treatment for eating disorders and obesity. To study the role of endogenous ghrelin in feeding performance further, we generated ghrelin-deficient (ghrl(-/-)) mice. Unexpectedly, ghrl(-/-) mice exhibited normal growth, cumulative food intake, reproduction, histological characters, and serum parameters. There were no differences in feeding patterns between ghrl(+/+) and ghrl(-/-) mice. Ghrl(-/-) mice displayed normal responses to scheduled feedings as seen for ghrl(+/+) mice. Memory-related feeding performances of ghrl(-/-) mice were indistinguishable from ghrl(+/+) littermates. These data indicate that ghrelin is not critical for feeding performance.

Circadian-dependent learning and memory enhancement in nociceptin receptor-deficient mice with a novel KUROBOX apparatus using stress-free positive cue task.

Using the novel apparatus KUROBOX, learning and memory behaviors, as well as various parameters of movement activity, were reevaluated in mice deficient for nociceptin/orphanin FQ receptor (NOP-/- mice) or mu-opioid receptor (MOP-/- mice). This method has the advantages that no handling procedures are required throughout the experiments performed over 3 days, positive cue paradigms are used without water or shock stress, and the method does not disturb the nocturnal habit of mice. NOP-/- mice displayed a significant enhancement of learning and memory under stress-free conditions, but there were no changes in the various physical and psychological parameters of movement activity (nest stay ratio, distance moved, speed and angle in the movement) and biological rhythm that were measured. Enhancement of nocturnal learning was observed during the first 12-h dark cycle, and enhancement of memory was observed at the beginning of the second dark cycle in NOP-/- mice. In contrast, MOP-/- mice showed no significant change in learning and memory behaviors or in physical and psychological parameters of movement activity, except for speed, MOP-/- mice showed a significant decrease in speed of movement. Thus, the KUROBOX apparatus provides a useful alternative method to evaluate learning and memory activity under the more physiological conditions. In addition, this apparatus has an advantage that various physical and psychological parameters of movement activity affecting learning and memory behavior are also evaluated at the same time.

Leg fat percentage correlates negatively with coronary atherosclerosis.

BACKGROUND: Visceral fat is related to coronary atherosclerosis, but little is known about the relation between coronary atherosclerosis and percent body fat accumulated in different parts of the body. METHODS AND RESULTS: The subjects were 100 consecutive patients with demonstrated electrocardiographic ischemic changes. Coronary atherosclerosis was assessed using Gensini's coronary score (CS), and for body fat distribution dual energy X-ray absorptiometry was used. The parameters measured were serum lipid concentrations, body weight, body mass index, percent total fat, trunk fat percent, arm fat percent and leg fat percent. Trunk fat percent correlated significantly with CS (p<0.01), and concentrations of low-density lipoprotein cholesterol (LDL-C) (p<0.01) and very low-density lipoprotein cholesterol (VLDL-C) (p<0.05) in men and women. Leg fat percent correlated negatively with CS in both men and women (p<0.01 for each). Concentrations of both LDL-C and VLDL-C correlated positively with CS in both men and women (p<0.01). CONCLUSION: There is a difference between the effect of body fat in the legs and the trunk that suggests leg fat has an anti-atherosclerotic effect and a negative correlation with CS, and conversely, that trunk fat has a pro-atherosclerotic effect and correlates positively with CS.

Neuromedin U has a novel anorexigenic effect independent of the leptin signaling pathway.

Neuromedin U (NMU) is a hypothalamic neuropeptide that regulates body weight and composition. Here we show that mice lacking the gene encoding NMU (Nmu(-/-) mice) develop obesity. Nmu(-/-) mice showed increased body weight and adiposity, hyperphagia, and decreased locomotor activity and energy expenditure. Obese Nmu(-/-) mice developed hyperleptinemia, hyperinsulinemia, late-onset hyperglycemia and hyperlipidemia. Notably, however, treatment with exogenous leptin was effective in reducing body weight in obese Nmu(-/-) mice. In addition, central leptin administration did not affect NMU gene expression in the hypothalamus of rats. These results indicate that NMU plays an important role in the regulation of feeding behavior and energy metabolism independent of the leptin signaling pathway. These characteristic functions of NMU may provide new insight for understanding the pathophysiological basis of obesity.

A new-generation apparatus for studying memory-related performance in mice.

1. We developed a new kind of food search test that can measure murine nocturnal memory without handling hard work for setting up. 2. This apparatus has four food stations, but only one station had accessible food at any time. The one station with accessible food was changed at 4-h intervals. 3. We compared the performance of transient forebrain global Ischemic mice, which are a hippocampal lesion model, with the performance of control C57BL/6J mice. 4. The correct visit ratio, i.e., the ratio of the number of visits to the correct food station to the number of visits to all stations, gradually increased in the control mice, but did not change in the Ischemic mice. 5. This new system was demonstrated to be an additional and useful tool for studying memory-related performance in mice.