Melatonin reverses depressive and anxiety like-behaviours induced by diabetes: involvement of oxidative stress, age, rage and S100B levels in the hippocampus and prefrontal cortex of rats.

Diabetes is associated with depression and anxiety symptoms. The current investigation was designed to explore the effect of melatonin on depressive and anxiety like-behaviours, oxidative stress, levels of AGE, RAGE and S100B in streptozotocin-induced diabetic rats. The animals were divided into four groups: Normoglycemic; Normoglycemic + melatonin; diabetic; diabetic + melatonin (10 mg/kg, for 4 weeks). The malondialdehyde (MDA), reduced glutathione (GSH), AGE, RAGE and S100B were measured and the depressive and anxiety like-behaviours were assessed by forced swimming and elevated plus maze tests, respectively. Melatonin ameliorates depressive and anxiety like-behaviours. Concomitantly, melatonin reversed diabetes induced increase of MDA, AGE and decrease of GSH and S100B levels in the hippocampus and prefrontal cortex. In conclusion, our results showed that melatonin administration may exert antidepressant-like and anxiolytic effects in diabetic rats through normalising of AGE/RAGE, S100B and oxidative stress in the prefrontal cortex and hippocampus.

The effects of glucagon-like peptide 1 receptor agonist (exenatide) on memory impairment, and anxiety- and depression-like behavior induced by REM sleep deprivation.

Previous investigations have shown that REM sleep deprivation impairs the hippocampus-dependent memory, long-term potentiation and causing mood changes. The aim of the present study was to explore the effects of exenatide on memory performance, anxiety- and depression like behavior, oxidative stress markers, and synaptic protein levels in REM sleep deprived rats. A total of 40 male Wistar rats were randomly divided to control, exenatide-treated control, sleep deprivation (SD), wide platform (WP) and exenatide-treated SD groups. During experiments, exenatide treatment (0.5 µg/kg, subcutaneously) was applied daily in a single dose for 9 days. Modified multiple platform method was employed to generate REM sleep deprivation for 72 h. The Morris water maze test was used to assess memory performance. Anxiety- and depression-like behaviors were evaluated by open field test (OFT), elevated plus maze (EPM) forced swimming test (FST), respectively 72 h after REMSD. The levels of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and postsynaptic density proteins 95 (PSD95) were measured in tissues of hippocampus and prefrontal cortex. The content of malondialdehyde (MDA) and reduced glutathione (GSH) were also measured. In the present study, an impairment in memory was observed in SD rats at the 24th hour of SD in compare to those of other groups. REMSD increased depression-like behavior in FST as well as the number of rearing and crossing square in OFT. Anxiety is the most common comorbid condition with depressive disorders. Contents of CaMKII and PSD95 decreased in hippocampus of SD rats. Exenatide treatment improved the impaired memory of SD rats and increased CaMKII content in hippocampus There was no difference in MDA and GSH levels among groups. Exenatide treatment also diminished locomotor activity in OFT. In conclusion, treatment with exenatide, at least in part, prevented from these cognitive and behavioral changes possibly through normalizing CaMKII levels in the hippocampus.

Protective effect of metformin against ovariectomy induced depressive- and anxiety-like behaviours in rats: role of oxidative stress.

Several studies have shown that low estrogen levels can lead to an increase in the incidence of depression and anxiety during menopause. The hippocampus and prefrontal cortex are parts of the brain involved in depressive- and anxiety-like behaviors. Recent studies have revealed that metformin has neuroprotective effects mainly due to its antioxidant properties. The aim of the present study was to examine the therapeutic potential of metformin in depressive- and anxiety-like behavior as well as oxidative stress in the prefrontal cortex and hippocampus of ovariectomized rats. Young female Wistar Albino rats were distributed into four groups (n:8): control, metformin-administered control, ovariectomized and metformin administered ovariectomized groups. Metformin (25 mg/kg) was administered daily by oral gavage for 2 weeks. Forced swimming test and open field test were performed to evaluate depression- and anxiety-like behaviors, respectively. Following the treatment with metformin, the tissues of the hippocampus and prefrontal cortex were isolated for the measurement of malondialdehyde, reduced glutathione and ascorbic acid contents. Ovariectomy resulted in depressive- and anxiety-like behaviors, and besides, increased content of malondialdehyde in both prefrontal cortex and hippocampus. The levels of ascorbic acid and glutathione were found to be reduced in ovariectomized rats. Metformin treatment significantly decreased depressive behaviour and malondialdehyde content in the prefrontal cortex. Reducing oxidative stress of the prefrontal cortex was suggested as a possible mechanism implicated in the beneficial effects of metformin on ovariectomy-induced depressive-like behaviour. We believe that the therapeutic efficiency of metformin needs to be tested for potential clinical use in surgical menopause or gonadal hormone deficiency women with depression.