Hippocampal and motor fronto-cortical neuroligin1 is increased in an animal model of depression.

Neuroligins (NLGNs) regulate synaptic excitability, neuronal signaling and sleep. We hypothesize that alteration of NLGNs is involved in the pathology of depression and tested the hypothesis in a model of depression using Wistar Kyoto (WKy) rat and its control, the Wistar (Wis) rat. We first evaluated behavioral deficits using the forced swim test and then characterized alterations of NLGN1 and NLGN2 with RT-PCR and Western Blotting in the prefrontal cortex, motor frontal cortex and hippocampus. Compared with controls of Wis rats, (1) the WKy rats had significantly shorter swim time and longer immobile time; (2) NLGN1 mRNA levels was higher in the motor frontal cortex and hippocampus in the WKy model; (3) NLGN1 protein was significantly higher in the motor frontal cortex, the prefrontal cortex and the hippocampus in the WKy model; (4) NLGN2 mRNA was significantly higher in the motor frontal cortex but significantly lower in the hippocampus in the WKy model. We concluded that NLGN1 gene and protein expression is higher in the motor frontal cortex, hippocampus and in the prefrontal cortex in the WKy rats suggesting that alterations of NLGN1 is involved in the pathology of depression but need to be further evaluated in human.

7,8-Dihydroxyflavone reduces sleep during dark phase and suppresses orexin A but not orexin B in mice.

Brain-derived neurotrophic factor (BDNF) binds to Tropomyosin-receptor-kinase B (TrkB) receptors that regulate synaptic strength and plasticity in the mammalian nervous system. 7,8-Dihydroxyflavone (DHF) is a recently identified small molecule Trk B agonist that has been reported to ameliorate depression, attenuate the fear response, improve memory consolidation, and exert neuroprotective effects. Poor and disturbed sleep remains a symptom of major depressive disorder and most current antidepressants affect sleep. Therefore, we conducted sleep/wake recordings and concomitant measurement of brain orexins, endogenous peptides that suppress sleep, in mice for this study. Baseline polysomnograph recording was performed for 24 h followed by treatment with either 5 mg/kg of DHF or vehicle at the beginning of the dark phase. Animals were sacrificed the following day, one hour after the final treatment with DHF. Orexin A and B were quantified using ELISA and radioimmunoassay, respectively. Total sleep was significantly decreased in the DHF group, 4 h after drug administration in the dark phase, when compared with vehicle-treated animals. This difference was due to a significant decrease of non-rapid eye movement sleep, but not rapid eye movement sleep. DHF increased power of alpha and sigma bands but suppressed power of gamma band during sleep in dark phase. Interestingly, hypothalamic levels of orexin A were also significantly decreased in the DHF group (97 pg/mg) when compared with the vehicle-treated group (132 pg/mg). However, no significant differences of orexin B were observed between groups. Additionally, no change was found in immobility tests.