Ablated Sonic Hedgehog Signaling in the Dentate Gyrus of the Dorsal and Ventral Hippocampus Impairs Hippocampal-Dependent Memory Tasks and Emotion in a Rat Model of Depression.

Specific memory processes and emotional aberrations in depression can be attributed to the different dorsal-ventral regions of the hippocampus. However, the molecular mechanisms underlying the differential functions of the dorsal hippocampus (dHip) and ventral hippocampus (vHip) remain unclear. As Sonic Hedgehog (Shh) is involved in the dorsal-ventral patterning of the neural tube and its signaling is dysregulated by chronic unpredictable mild stress (CUMS), we investigated its role in influencing the differential functions of the dHip and vHip. Here, CUMS downregulated the expression of Shh signaling markers, including Shh and its downstream effectors GLI family zinc finger 12 (Gli1/2), Patched (Ptch), and smoothened (Smo), in both the dHip and vHip of rats, though more so in the vHip. Additionally, Shh knockdown in the dorsal or ventral dentate gyrus (DG) resulted in restrained neurogenic activity in newborn neurons, especially in immature neurons through decreased expression of Shh signaling markers. Furthermore, Shh knockdown in the DG of the dHip led to memory impairment by inhibiting experience-dependent activation of immature neurons, whereas its knockdown in the DG of the vHip led to an emotional handicap by delaying the maturation of immature neurons. Finally, Shh knockdown in either the dDG or vDG of hippocampus abolished the corresponding cognitive enhancement and emotional recovery of fluoxetine. In conclusion, Shh is essential to maintain the functional heterogeneity of dHip and vHip in depressed rat, which was mainly mediating by local changes of dependent activation and maturity of immature neurons, respectively.

Integrating serum metabolomics and network analysis to explore the antidepressant activity of crocin in rats with chronic unexpected mild stress-induced depression.

CONTEXT: Crocin exhibits anti-depressant properties. However, its underlying mechanisms and its relationship with metabolomics remain unclear. OBJECTIVE: This study elucidates the mechanism of action and potential targets of crocin in treating chronic unexpected mild stress (CUMS)-induced depression in rats. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats underwent 4 weeks of CUMS to establish the depression model. The normal control (distilled water), crocin (25 mg/kg), and fluoxetine (5.4 mg/kg) groups were orally administered for 4-weeks. Behavioural tests evaluated the effects of crocin, while liquid chromatography-mass spectrometry metabolomics identified differential metabolites and their associated metabolic pathways. Subsequently, network pharmacology was utilized to predict the targets of crocin. RESULTS: Crocin significantly increased body weight (from 319.16 ± 4.84 g to 325.67 ± 2.84 g), sucrose preference (from 0.46 ± 0.09 to 0.70 ± 0.09), vertical activity (from 2.83 ± 1.94 to 8 ± 2.36), horizontal activity (from 1 ± 0.63 to 4.5 ± 3.08) and decreased immobilization time (from 13.16 ± 2.69 to 3.97 ± 3.00). Metabolomics analysis identified 7 metabolites and 5 associated metabolic pathways. From the combined analysis of network pharmacology and metabolomics, three targets (PRMT1, CYP3A4, and GLB1) are the overlapping targets and the two most important metabolic pathways are tryptophan metabolism and glycerolipid metabolism. DISCUSSION AND CONCLUSIONS: This study provides insights into the antidepressant therapeutic effect of crocin and its underlying mechanisms. The findings contribute to a better understanding of the metabolic mechanism involved in the anti-depressant effect of crocin, establishing a strong foundation for future research in this area.

Expression of connexin 36 in central nervous system and its role in epileptic seizure.

OBJECTIVE: This review discusses the experimental and clinical studies those show the expression of connexin 36 in the central nervous system and the possible role of connexin 36 in epileptic seizure. DATA SOURCES: All articles used in this review were mainly searched from PubMed published in English from 1996 to 2012. STUDY SELECTION: Original articles and reviews were selected if they were related to the expression of connexin 36 in the central nervous system and its role in epilepsy. RESULTS: The distribution of connexin 36 is developmentally regulated, cell-specific and region-specific. Connexin 36 is involved in some neuronal functions and epileptic synchronization. Changes in the connexin 36 gene and protein were accompanied by seizures. Selective gap junction blockers have exerted anticonvulsant actions in a variety of experiments examined in both humans and experimental animals. CONCLUSIONS: Connexin 36 plays an important role in both physiological and pathological conditions in the central nervous system. A better understanding of the role of connexin 36 in seizure activity may contribute to the development of new therapeutic approaches to treating epilepsy.