JournalTOCs School of Mathematical and Computer Sciences Heriot-Watt University Edinburgh, EH14 4AS, UK Email: journaltocs@hw.ac.uk Tel: +00 44 (0)131 4513762  Your IP address: 35.171.45.182 |
JournalTOCs School of Mathematical and Computer Sciences Heriot-Watt University Edinburgh, EH14 4AS, UK Email: journaltocs@hw.ac.uk Tel: +00 44 (0)131 4513762 Your IP address: 35.171.45.182 |
Hybrid journal (It can contain Open Access articles)
Depression is a common mood disorder and many patients do not respond to conventional pharmacotherapy or experience a variety of adverse effects. This work proposed that riparin I (RIP I) and riparin II (RIP II) present neuroprotective effects through modulation of astrocytes and microglia, resulting in the reversal of depressive-like behaviors. To verify our hypothesis and clarify the pathways underlying the effect of RIP I and RIP II on neuroinflammation, we used the chronic unpredictable mild stress (CUMS) depression model in mice. Male Swiss mice were exposed to stressors for 28 days. From 15th to the 22nd day, the animals received RIP I or RIP II (50 mg/kg) or fluoxetine (FLU, 10 mg/kg) or vehicle, by gavage. On the 29th day, behavioral tests were performed. Expressions of microglia (ionized calcium-binding adaptor molecule-1 – Iba-1) and astrocyte (glial fibrillary acidic protein – GFAP) markers and levels of cytokines tumor necrosis factor alfa (TNF-α) and interleukin 1 beta (IL-1β) were measured in the hippocampus. CUMS induced depressive-like behaviors and cognitive impairment, high TNF-α and IL-1β levels, decreased GFAP, and increased Iba-1 expressions. RIP I and RIP II reversed these alterations. These results contribute to the understanding the mechanisms underlying the antidepressant effect of RIP I and RIP II, which may be related to neuroinflammatory suppression.
Increasing evidence indicates that neuroinflammation, oxidative stress, and neurotrophic factors play a key role in the pathophysiology of major depressive disorder (MDD). In addition, the attenuation of inflammatory response has been considered a putative mechanism for MDD treatment. PT-31 is an imidazolidine derivative and a putative α₂-adrenoceptor agonist that has previously demonstrated antinociceptive activity. The present study aimed to investigate the effect of PT-31 on depressive-like behavior and lipopolysaccharide-induced neurochemical changes. To this end, mice received intraperitoneally saline or lipopolysaccharide (600 µg/kg), and 5 h postinjection animals were orally treated with saline, PT-31 (3, 10, and 30 mg/kg), or fluoxetine (30 mg/kg). Mice were subjected to the open field test (OFT) 6 and 24 h after lipopolysaccharide administration and to the tail suspension test (TST) 24 h postlipopolysaccharide. Subsequently, animals were euthanized, and brains were dissected for neurochemical analyses. The administration of lipopolysaccharide-induced sickness- and depressive-like behaviors, besides promoting an increase in myeloperoxidase activity and a reduction in brain-derived neurotrophic factor (BDNF) levels. Noteworthy, PT-31 3 mg/kg attenuated lipopolysaccharide-induced decreased locomotor activity 6 h after lipopolysaccharide in the OFT. All tested doses of PT-31 significantly reduced the immobility time of animals in the TST and attenuated lipopolysaccharide-induced increased myeloperoxidase activity in the cortex of mice. Our results demonstrate that PT-31 ameliorates behavioral changes promoted by lipopolysaccharide in OFT and TST, which is possibly mediated by attenuation of the inflammatory response.
Diazepam administration has been shown to influence the release of histamine in various brain areas involved in motor behavior. Therefore, the present study explored the plausible regulatory role of the central histaminergic system in diazepam-induced deficits in motor performance in mice using the rota-rod and beam walking tests. In this study, several doses of diazepam (0.5, 1, 2, and 3 mg/kg, i.p.) were assessed in mice for changes in motor performance on the rota-rod and beam walking test. In addition, the brain histamine levels were determined after diazepam administration, and the diazepam-induced motor deficits were assessed in mice, pretreated centrally (intracerebroventricular) with histaminergic agents such as histamine (0.1, 10 µg), histamine precursor (L-histidine: 0.1, 2.5 µg), histamine neuronal releaser/H3 receptor antagonist (thioperamide: 0.5, 10 µg), H1 and H2 receptor agonist [2-(3-trifluoromethylphenyl) histamine (FMPH: 0.1, 6.5 µg; amthamine: 0.1, 5 µg)/antagonist (H1: cetirizine 0.1 µg) and (H2: ranitidine: 50 µg)]. Results indicate that mice treated with diazepam at doses 1, 2 mg/kg, i.p. significantly increased the brain histamine levels. Moreover, in mice pretreated with histaminergic transmission-enhancing agents, the diazepam (2 mg/kg, i.p.)-induced motor incoordination was significantly reversed. Contrastingly, diazepam (1 mg/kg, i.p.) in its subeffective dose produced significant motor deficits in mice preintracerebroventricular injected with histamine H1 and H2 receptor antagonists on both the employed tests. Therefore, it is postulated that endogenous histamine operates via H1 and H2 receptor activation to alleviate the motor-impairing effects of diazepam.
Emerging evidence suggests that crocin rescues stress-induced depressive symptoms in mice via stimulation of hippocampal neurogenesis. Glutamate modulators mainly involving N-methyl-d-aspartate (NMDA) receptors (NMDARs) have highlighted a role in neural development, synaptic plasticity, and depression. The research presented here was designed to appraise the interaction between NMDAR agents and crocin on depressive-related behaviors in the NMRI male mice exposed to acute restraint stress (ARS) for a period of 4 h. The mice were submitted to the splash test, forced swimming test, and tail suspension test to evaluate depressive-like behavior. The ARS decreased the grooming duration in the splash test and increased immobility time in the forced swimming test and tail suspension test, suggesting a depressive-like phenotype. NMDA (0.25 and 0.5 μg/mouse, intracerebroventricular) did not alter depression-related profiles in both non–acute restraint stress (NARS) and ARS mice, while the same doses of NMDAR antagonist D-AP5 potentiated the antidepressive-like activities in the ARS mice compared with the NARS mice. Moreover, a low dose of NMDA did not change depression-related parameters in the crocin-treated NARS or ARS mice, while D-AP5 enhanced the crocin response in the NARS and ARS mice. Isobologram analysis noted a synergism between crocin and D-AP5 on antidepressive-like behavior in the NARS and ARS mice. Collectively, the combination of crocin and D-AP5 was shown to mitigate depression symptoms and can be potentially used for the treatment of depression disorders.
