Light-intensity exercise improves memory dysfunction with the restoration of hippocampal MCT2 and miRNAs in type 2 diabetic mice.

Cognitive decline associated with type 2 diabetes mellitus (T2DM) is a risk factor to impair human health. Although light-intensity exercise prevents hippocampal memory dysfunction in pre-symptomatic T2DM animals by altering hippocampal lactate transport and neurotrophic factors, the effects of light-intensity exercise in an advanced stage of T2DM animals remain unclear. Here, ob/ob mice, an animal model of T2DM, were subjected to light-intensity exercise (5.0 m/min) for 30 min/day, five days/week for four weeks. The effects of light-intensity exercise on hippocampal complications, mRNA expressions of monocarboxylate transporter (MCT), and miRNA levels were assessed. The light-intensity exercise improved hippocampal memory retention in ob/ob mice. Downregulated hippocampal Mct2 mRNA levels in T2DM were improved with light-intensity exercise. Hippocampal mRNA levels of Mct1 and Mct4 were unchanged within groups. Based on miRNA sequencing, sedentary ob/ob mice exhibited that 71 miRNAs were upregulated, and 77 miRNAs were downregulated in the hippocampus. In addition, the exercise significantly increased 24 miRNAs and decreased 4 miRNAs in the T2DM hippocampus. The exercise reversed T2DM-induced alterations of hippocampal 9 miRNAs, including miR-200a-3p. Our findings imply that miR-200a-3p/Mct2 in the hippocampus would be a possible clinical target for treating T2DM-induced memory dysfunction.

Differential working memory function between phonological and visuospatial strategies: a magnetoencephalography study using a same visual task.

Previous studies have reported that, in working memory, the processing of visuospatial information and phonological information have different neural bases. However, in these studies, memory items were presented via different modalities. Therefore, the modality in which the memory items were presented and the strategy for memorizing them were not rigorously distinguished. In the present study, we explored the neural basis of two working memory strategies. Nineteen right-handed young adults memorized seven sequential directions presented visually in a task in which the memory strategy was either visuospatial or phonological (visuospatial/phonological condition). Source amplitudes of theta-band (5-7 Hz) rhythm were estimated from magnetoencephalography during the maintenance period and further analyzed using cluster-based permutation tests. Behavioral results revealed that the accuracy rates showed no significant differences between conditions, while the reaction time in the phonological condition was significantly longer than that in the visuospatial condition. Theta activity in the phonological condition was significantly greater than that in the visuospatial condition, and the cluster in spatio-temporal matrix with p < 5% difference extended to right prefrontal regions in the early maintenance period and right occipito-parietal regions in the late maintenance period. The theta activity results did not indicate strategy-specific neural bases but did reveal the dynamics of executive function required for phonological processing. The functions seemed to move from attention control and inhibition control in the prefrontal region to inhibition of irrelevant information in the occipito-parietal region.

Low-Carbohydrate and High-Protein Diet Suppresses Working Memory Function in Healthy Mice.

Low-carbohydrate and high-protein (LC-HP) diets are acceptable for improving physiological and metabolic parameters. However, the effects of LC-HP diets on the brain are unclear, which depend on glycometabolism for neuronal activity. Since astrocyte-neuron lactate shuttle (ANLS) is an essential pathway for maintaining brain functions, we investigated the changes in hippocampal memory function. In addition, the alteration of lactate transporter constituting ANLS and ANLS-related neurotrophic factors by feeding LC-HP diets was evaluated in healthy mice. C57BL/6 mice were divided into two groups: a group feeding LC-HP diet (24.6% carbohydrate, 57.6% protein, and 17.8% fat as percentages of calories) and a group feeding control diet (58.6% carbohydrate, 24.2% protein, and 17.2% fat as percentages of calories). Here, we found that 4 wk of LC-HP diet feeding suppressed memory function in mice evaluated by Y-maze. Hippocampal mRNA levels of lactate transporters, such as Mct1, Mct4, and Mct2, were unchanged with feeding LC-HP diets; however, LC-HP diets significantly decreased Dcx and Igf-1 receptor mRNA levels in the hippocampus. Bdnf and its related signaling in mice hippocampus exhibited no change by LC-HP diets. Although there was non-influence in the lactate-transport system, LC-HP diets would suppress hippocampal working memory with dysregulation of neuroplasticity. The current data propose the importance of food choices for maintaining hippocampal health.

Four weeks of light-intensity exercise enhances empathic behavior in mice: The possible involvement of BDNF.

Empathy is one of the essential functions of mammals for maintaining relationships with others. Physical activity contributes to enhancing empathic attitude and behavior; however, it is remained to cover the effective intensity of exercise on mammal empathy. Here, we tested the effects of light-intensity exercise, which has beneficial effects on expressing neurotrophic factors in the brain, on empathic behavior. Eight-week-old male C57BL/6 mice were subjected to forced wheel running at light-intensity (7.0 m/min, 30 min/day, 5 days/week) for 4 weeks. Then, all mice were subjected to helping behavior to evaluate their empathic behavior. The insular cortex was collected for analyzing the expressions of mRNA and miRNA. Four weeks of light-intensity exercise enhanced helping behavior. Exercised mice exhibited higher Bdnf gene expressions in the insular cortex than sedentary mice. In addition, there was a significant positive correlation between mRNA levels of Fndc5 and Bdnf in the insular cortex. Based on miRNA sequencing, 26 out of 51 miRNAs were significantly upregulated, and 25 out of 51 miRNAs were significantly downregulated in the insular cortex of mice with exercise. There were significant correlations between 11 out of 51 miRNAs and helping behavior; miR-486a-3p, which relates to FNDC5 expression, was contained. These results imply that miR-486a-3p/Fndc5/Bdnf pathway in the insular cortex would be a possible target for treating empathy.

Physical activity associates empathy in Japanese young adults with specific gene variations of oxytocin receptor and vasopressin V1B receptor.

BACKGROUND: Empathy, consisting of cognitive empathy and affective empathy, is essential for creating relationships with others. Since the genetic polymorphism of oxytocin receptor (OXTR) and arginine-vasopressin V1B receptor (AVPR1B) relate to prosocial behavior and empathy, it would need to innovate strategies for treating human empathy by considering individual genetic variations. Physical activity is expected as a possible strategy; here, we investigated the influences of genetic polymorphisms in OXTR SNP rs53576 and AVPR1B SNP rs28373064, on the relationships of self-reported empathy with physical activity. METHODS: The saliva is collected from a hundred Japanese college students for determining the individual polymorphism of OXTR SNP rs53576 (AA, AG, or GG genotype) and AVPR1B SNP rs28373064 (TT, TC, or CC genotype). In addition, the participants' self-reported cognitive and affective empathy, amounts of physical activity, and sitting time were evaluated with questionaries. RESULTS: The participants with OXTR SNP rs53576 GG genotype showed a significant negative correlation between sitting time and cognitive empathy adjusted by age, gender, and sports experience. Further, there was a trend to correlate between physical activity amounts and cognitive empathy in the participants carrying the G variant in OXTR SNP rs53576 (AG or GG). As for AVPR1B SNP rs28373064, the persons with TT genotype exhibited a negative correlation trend between sitting time and cognitive empathy. CONCLUSIONS: There are possible correlations between the self-reported cognitive empathy and physical activity amounts in the persons carrying the G variant of OXTR rs53576 or with the TT genotype for AVPR1B SNP rs28373064.