TGR5-mediated lateral hypothalamus-dCA3-dorsolateral septum circuit regulates depressive-like behavior in male mice.

Although bile acids play a notable role in depression, the pathological significance of the bile acid TGR5 membrane-type receptor in this disorder remains elusive. Using depression models of chronic social defeat stress and chronic restraint stress in male mice, we found that TGR5 in the lateral hypothalamic area (LHA) predominantly decreased in GABAergic neurons, the excitability of which increased in depressive-like mice. Upregulation of TGR5 or inhibition of GABAergic excitability in LHA markedly alleviated depressive-like behavior, whereas down-regulation of TGR5 or enhancement of GABAergic excitability facilitated stress-induced depressive-like behavior. TGR5 also bidirectionally regulated excitability of LHA GABAergic neurons via extracellular regulated protein kinases-dependent Kv4.2 channels. Notably, LHA GABAergic neurons specifically innervated dorsal CA3 (dCA3) CaMKIIα neurons for mediation of depressive-like behavior. LHA GABAergic TGR5 exerted antidepressant-like effects by disinhibiting dCA3 CaMKIIα neurons projecting to the dorsolateral septum (DLS). These findings advance our understanding of TGR5 and the LHAGABA→dCA3CaMKIIα→DLSGABA circuit for the development of potential therapeutic strategies in depression.

[Continuous-rain hazard of transplanting and direct-sowing rice in Sichuan Basin, China]. / å››å·ç›†åŒºç›´æ’­å’Œç§»æ ½æ°´ç¨»çš„è¿žé˜´é›¨ç¾å®³å±é™©æ€§.

Continuous rain disaster is a kind of complex disaster with high frequency in the Basin area of Sichuan Province. Continuous rainy weather may appear in every growing stage of rice, with consequences on the yield and quality. Based on the meteorological data of 105 meteorological stations between 1981 and 2019, combining the observation data of rise production, agricultural statistics and the basic geographic information, we quantitatively evaluated and compared the continuous-rain disasters in the whole growth period and the four growth stages (sowing-jointing, jointing-booting, booting-early filling, mid-late filling-maturity) between transplanted rice and direct-seeded rice in the basin area of Sichuan Province. The results showed that the disaster index of continuous-rain for rice was higher in the sowing-jointing stage and the mid-late filling-maturity stage, higher in the northern and southwest edges of the basin, and lower in the middle, western and southern basin. The area with high-risk was relatively limited, which concentrated in the northern edge of the basin and scattered in the southern region of the basin. The low-risk area was the most widely distributed, which concentrated in the western and central parts of the basin. The total area of high-disaster areas for transplanted rice was 2.4 times as large as that for direct-seeded rice.

Helicid Ameliorates Learning and Cognitive Ability and Activities cAMP/PKA/CREB Signaling in Chronic Unpredictable Mild Stress Rats.

Helicid (4-formylphenyl-O-ß-D-allopyranoside), an active component found in seeds from the Chinese herb Helicia nilagirica, has been reported to exert sedative, analgesic, hypnotic and antidepressant effects. The present study was designed to evaluate the antidepressant, learning and cognitive improvement effects of helicid in a chronic unpredictable mild stress (CUMS) model of depression in rats and to explore cAMP/protein kinase A (PKA)/cAMP response element-binding (CREB) signaling pathway. Sprague-Dawley rats were randomly assigned to six groups (n = 10): control; CUMS; CUMS + fluoxetine (5 mg/kg) and CUMS + helicid at 8, 16 and 32 mg/kg. All rats were subjected to 12 weeks of CUMS protocols and drug administration during the last 6 weeks of CUMS. Our results showed that helicid, at a dose of 32 mg/kg, significantly reversed decreases in body weight and sucrose consumption, increased the distance and number of crossings in the open-field test (OFT), reduced immobility times in the forced swimming test (FST) and improved spatial memory in the Morris water maze (MWM); all of these effects had been induced by CUMS paradigm. Immunohistochemistry showed that administration of helicid could promoted the proliferation of neurons in the hippocampal CA1 and dentate gyrus (DG) regions. CUMS rats treated with helicid had dramatically decreased protein levels of serotonin transporters (SERTs). In addition, CUMS resulted in a significant reduction in the expression of cAMP, PKA C-α and p-CREB, each of which were partially attenuated by helicid administration. These results indicated that helicid could improve depressive behaviors, learning and cognitive deficits and increase hippocampal neurogenesis, which may be mediated by the regulation of SERTs, activation of the cAMP/PKA/CREB signaling pathway and upregulation of p-CREB levels in hippocampal.