Astrocytic pyruvate dehydrogenase kinase-2 is involved in hypothalamic inflammation in mouse models of diabetes.

Hypothalamic inflammation plays an important role in disrupting feeding behavior and energy homeostasis as well as in the pathogenesis of obesity and diabetes. Here, we show that pyruvate dehydrogenase kinase (PDK)-2 plays a role in hypothalamic inflammation and its sequelae in mouse models of diabetes. Cell type-specific genetic ablation and pharmacological inhibition of PDK2 in hypothalamic astrocytes suggest that hypothalamic astrocytes are involved in the diabetic phenotype. We also show that the PDK2-lactic acid axis plays a regulatory role in the observed metabolic imbalance and hypothalamic inflammation in mouse primary astrocyte and organotypic cultures, through the AMPK signaling pathway and neuropeptidergic circuitry governing feeding behavior. Our findings reveal that PDK2 ablation or inhibition in mouse astrocytes attenuates diabetes-induced hypothalamic inflammation and subsequent alterations in feeding behavior.

Chronic sleep deprivation-induced proteome changes in astrocytes of the rat hypothalamus.

Sleep deprivation (SD) can influence cognition, memory, and sleep/wake homeostasis and can cause impairments in many physiological processes. Because the homeostatic control of the sleep/wake cycle is closely associated with the hypothalamus, the current study was undertaken to examine proteomic changes occurring in hypothalamic astrocytes following chronic partial SD. After chronic partial SD for 7 days, astrocytes were prepared from rat hypothalamus using a Percoll gradient method, and their proteome profiles were determined by LC-MS/MS. Comparisons of the proteome profiles of hypothalamic astrocytes revealed that chronic partial SD increased (≥1.5-fold) 89 proteins and decreased (≤0.7-fold) 50 proteins; these changes in protein expression were validated by western blot or immunohistochemistry. DAVID and IPA analyses of these proteins suggested that SD may influence gliotransmission and astrocyte activation. PPP2R1A, RTN4, VAMP-2, LGI-1, and SLC17A7 were identified and validated as the main targets of SD in astrocytes. Our results suggest that SD may modulate gliotransmission in the hypothalamus, thereby disturbing sleep/wake homeostasis and increasing susceptibility to neurological disease; however, further studies are required to confirm whether the proteome changes are specific to SD.

Ginsenoside Rh2 ameliorates scopolamine-induced learning deficit in mice.

To understand memory-enhancing effect of red ginseng biotransformed by Bifidobacterium longum H-1 (RGB), which more potently improved scopolamine-induced learning deficit than red ginseng in the preliminary experiment, its main constituents, ginsenosides Rb1, Rg3 and Rh2, were isolated and their memory-enhancing effects investigated in scopolamine-treated mice by using passive avoidance and Y-maze tests. Among them, ginsenoside Rh2 most potently reversed memory impairment caused by scopolamine. Ginsenoside Rh2 also significantly shortened the escape latencies prolonged by scopolamine in the Morris water maze test (p<0.001) and increased the swimming time shorten by scopolamine within the platform quadrant (p<0.05). The ginsenoside Rh2 (3 muM) reversed scopolamine (10 muM)-induced suppression of long-term potentiation. It recovered field excitatory post synaptic potential (fEPSP) amplitude potentiation to 152.3+/-8.7% of the control (p<0.05). Based on these findings, RGB and its main constituent, ginsenoside Rh2, might improve learning deficits. Also the memory-enhancing effects of RGB may be dependent on the content of ginsenoside Rh2.

Alpha neurofeedback improves the maintaining ability of alpha activity.

The effects of alpha-neurofeedback (ANF) on electroencephalographic alpha-activity were investigated. Each session consisted of a 2.5-min eye-opened state and 17.5-min of ANF, which was divided into 16 1.25-min bins. Alpha amplitudes were gradually increased as the session was repeated. The maximum value at the start of ANF gradually decreased as time passed, but the slowdown of alpha-activity during each session was decreased as the session was repeated. The correlation between alpha-activity at the end of ANF and at the following session's eye-opened state was highly significant. These results showed that ANF enhances the ability of alpha-activity to maintain itself rather than the increase of alpha-amplitude during intrasession and that the maintained alpha-activity during former training remained until the next session.