Agomelatine, a novel antidepressant with established clinical efficacy, acts as a melatonin receptor agonist and 5-HT(2C) receptor antagonist. As stress is a significant risk factor in the development of depression, we sought to determine if chronic agomelatine treatment would block the stress-induced impairment of memory in rats trained in the radial-arm water maze (RAWM), a hippocampus-dependent spatial memory task. Moreover, since neural cell adhesion molecule (NCAM) is known to be critically involved in memory consolidation and synaptic plasticity, we evaluated the effects of agomelatine on NCAM, and polysialylated NCAM (PSA-NCAM) expression in rats given spatial memory training with or without predator stress. Adult male rats were pre-treated with agomelatine (10 mg/kg i.p., daily for 22 d), followed by a single day of RAWM training and memory testing. Rats were given 12 training trials and then they were placed either in their home cages (no stress) or near a cat (predator stress). Thirty minutes later the rats were given a memory test trial followed immediately by brain extraction. We found that: (1) agomelatine blocked the predator stress-induced impairment of spatial memory; (2) agomelatine-treated stressed, as well as non-stressed, rats exhibited a rapid training-induced increase in the expression of synaptic NCAM in the ventral hippocampus; and (3) agomelatine treatment blocked the water-maze training-induced decrease in PSA-NCAM levels in both stressed and non-stressed animals. This work provides novel observations which indicate that agomelatine blocks the adverse effects of stress on hippocampus-dependent memory and activates molecular mechanisms of memory storage in response to a learning experience.
Carbon tetrachloride (CCl4) is a toxic chemical that causes liver injury. CCl4 triggers endoplasmic reticulum (ER) stress and unfolded protein response (UPR). UPR triggers autophagy to deal with the damage. The aim of this study was to investigate the effect of baicalein, derived from Scutellaria baicalensis, on CCl4-induced liver damage concerning ER stress and autophagy. Two groups of Wistar albino rats (n = 7/groups) were treated with 0.2 ml/kg CCl4 for 10 days with and without baicalein. Histological and transmission electron microscopy (TEM) analysis, autophagy, and ER stress markers measurements were carried out to evaluate the effect of baicalein. Histological examinations showed that baicalein reduced liver damage. TEM analysis indicated that baicalein inhibited ER stress and triggered autophagy. CCl4-induced elevation of C/EBP homologous protein (CHOP), glucose-regulating protein 78 (GRP78), activating transcription factor 4 (ATF4), activating transcription factor 6 (ATF6), inositol requiring enzyme 1 (IRE1), pancreatic ER kinase (PERK), and active/spliced form of X-box-binding protein 1 (XBP1s) ER stress markers were decreased by baicalein. Baicalein also increased the autophagy-related 5 (ATG5), Beclin1, and Microtubule-associated protein 1A/1B-light chain 3-phosphatidylethanolamine-conjugated form (LC3-II) autophagy marker levels. In conclusion, baicalein reduced the CCl4-induced liver damage by inhibiting ER stress and the trigger of autophagy.
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