Stress In Hippocampus Of Mice Research Articles

2, 3, 5, 4'-Tetrahydroxystilbene-2-O-β-D-glucoside prevention of lipopolysaccharide-induced depressive-like behaviors in mice involves neuroinflammation and oxido-nitrosative stress inhibition.

Although numerous hypotheses have been raised in recent years, the exact mechanisms that promote the development of major depression are largely unknown. Recently, strategies targeting the process of neuroinflammation and oxidative stress in depression have been attracting greater attention. 2, 3, 5, 4'-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG), a compound purified from a traditional Chinese herbal medicine polygonummultiflorum, has been widely reported to inhibit neuroinflammation and oxidative stress. In this context, we investigated whether TSG affects lipopolysaccharide (LPS)-induced depressive-like behaviors in a manner associated with neuroinflammation and oxido-nitrosative stress. Results showed that administration of ICR mice with 0.83 mg/kg of LPS-induced typical depressive-like behaviors in the experiments of the tail-suspension test, the forced-swimming test, and sucrose preference, and these behaviors were prevented by TSG treatment (30 and 60 mg/kg). Further analysis showed that TSG pretreatment at the doses of 30 and 60 mg/kg not only inhibited the production of proinflammatory cytokines induced by LPS, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α, but also prevented the LPS-induced enhancement of oxido-nitrosative stress in mouse hippocampus and prefrontal cortex. The LPS-induced decreases in brain-derived neurotrophic factor levels in the hippocampus and prefrontal cortex were also prevented by TSG treatment. Generally, our data provide evidence to show that TSG could be used to cope with depressive-like symptoms by inhibition of neuroinflammation and oxido-nitrosative stress.

Neuroprotective effects of N-adamantyl-4-methylthiazol-2-amine against amyloid β-induced oxidative stress in mouse hippocampus.

We previously reported that N-adamantyl-4-methylthiazol-2-amine (KHG26693) suppresses amyloid beta (Aβ)-induced neuronal oxidative damage in cortical neurons. Here we investigated the mechanism and antioxidative function of KHG26693 in the hippocampus of Aβ-treated mice. KHG26693 significantly attenuated Aβ-induced TNF-α and IL-1β enhancements. KHG26693 decreased Aβ-mediated malondialdehyde formation, protein oxidation, and reactive oxygen species by decreasing the iNOS level. KHG26693 suppressed Aβ-induced oxidative stress through a mechanism involving glutathione peroxidase, catalase, and GSH attenuation. Aβ-induced MMP-2, cPLA2, and pcPLA2 expressions were almost completely attenuated by KHG26693 treatment, suggesting that Aβ-induced oxidative stress reduction by KHG26693 is, at least partly, caused by the downregulation of MMP-2 and cPLA2 activation. Compared with Aβ treatment, KHG26693 treatment upregulated Nrf2 and HO-1 expressions, suggesting that KHG26693 protects the brain from Aβ-induced oxidative damage, likely by maintaining redox balance through Nrf2/HO-1 pathway regulation. KHG26693 significantly attenuated Aβ-induced oxidative stress in the hippocampus of Aβ-treated mice.

Effects of moderate exercise on cigarette smoke exposure-induced hippocampal oxidative stress values and neurological behaviors in mice

The objective of the present study was to investigate the effects of exercise training on behavior and neurochemical parameters in mice exposed to cigarette smoke. To this aim, mice (C57 BL6) male (30-35 g) were exposed to cigarette smoke 60 consecutive days three times a day and they were subjected to treadmill training 8 weeks for 5 days/week. For behavior assessment, mice were tested in the open-field and forced to a swim test. The superoxide anion, thiobarbituric acid reactive substances and protein carbonyl formation were measured as markers of oxidative stress in hippocampus of mice. In addition, the brain-derived neurotrophic factor (BDNF) levels were measured in the hippocampus samples. Cigarette smoke group and cigarette smoke plus exercise group, increased immobility time in forced swimming test in rats compared to the control group, without affecting spontaneous locomotor activity. There was an increase in the levels of superoxide, TBARS and of protein carbonyl and a decreased in BDNF levels in the hippocampus of rats exposed to cigarette smoke and cigarette smoke plus exercise. Exercise alone did not change any of the parameters evaluated in this study. In conclusion, we observed that physical training improves the oxidative stress parameters, but does not alter depressive-like behavior neither prevent the decreases in BDNF levels in hippocampus induced by cigarette smoke.

Upregulation of Myo6 expression after traumatic stress in mouse hippocampus

Traumatic stress has been believed to result in a variety of unusual alterations of the integrity and the functionality in the hippocampus. In this study, we searched for genes responsive to traumatic stress in the mouse hippocampus to elucidate the underlying mechanisms. Adult male mice were subjected to water-immersion restraint stress (WIRS) for 3h as an extremely stressful experience, followed by dissection of the hippocampus and subsequent extraction of RNA for differential display polymerase chain reaction (PCR) analysis. The actin-based molecular motor protein myosin VI (Myo6) was identified as a gene markedly upregulated by traumatic stress in the mouse hippocampus 24h after WIRS. Real-time PCR and Western blotting analyses clearly revealed a significant increase in the expression of both mRNA and corresponding protein for Myo6 in the hippocampus within 24h after WIRS, while WIRS failed to significantly affect the expression of Myo6 protein in the cerebral cortex, cerebellum and olfactory bulb. Immunohistochemistry analysis revealed that Myo6 protein was ubiquitously expressed throughout the mouse brain, with an extremely high level in the olfactory bulb. These results suggest that Myo6 may be selectively and rapidly upregulated to play a hitherto unidentified role in the maintenance of the integrity and functionality in the hippocampus after traumatic stress.

Kainic acid induces early and transient autophagic stress in mouse hippocampus

Kainic acid (KA) treatment is a well-established model of hippocampal neuron death mediated in large part by KA receptor-induced excitotoxicity. KA-induced, delayed neuron death has been shown previously to follow the induction of seizures and exhibit characteristics of both apoptosis and necrosis. Growing evidence supports a role of autophagic stress-induced death of neurons in several in vitro and in vivo models of neuron death and neurodegeneration. However, whether autophagic stress also plays a role in KA-induced excitotoxicity has not been previously investigated. To examine whether KA alters the levels of proteins associated with or known to regulate the formation of autophagic vacuoles, we isolated hippocampal extracts from control mice and in mice following 2–16h KA injection. KA induced a significant increase in the amount of LC3-II, a specific marker of autophagic vacuoles, at 4–6h following KA, which indicates a transient induction of autophagic stress. Levels of autophagy-associated proteins including ATG5 (conjugated to ATG12), ATG6 and ATG7 did not change significantly after treatment with KA. However, ratios of phospho-mTOR/mTOR were elevated from 6 to 16h, and ratios of phospho-Akt/Akt were elevated at 16h following KA treatment, suggesting a potential negative feedback loop to inhibit further stimulation of autophagic stress. Together these data indicate the transient induction of autophagic stress by KA which may serve to regulate excitotoxic death in mouse hippocampus.