Neuroscience
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The Na+/K+-ATPase is a transmembrane ion pump that has a critical homeostatic role within every mammalian cell; however, it is vulnerable to the effects of increased oxidative stress. Understanding how expression of this transporter is influenced by oxidative stress may yield insight into its role in the pathophysiology of neurological and neuropsychiatric diseases. In this study we investigated whether increased oxidative stress could influence Na+/K+-ATPase expression in various brain regions of mice. ⋯ Despite increased staining for oxidative stress in higher brain, no differences in α1 or α3 expression were noted in Aldh2-/- mice versus wildtype, or in mice exposed to a 28-day chronic unpredictable stress protocol. In both models of oxidative stress, gene and protein expression of Na+/K+-ATPase α1 and α3 isoforms within the higher and lower brain was remarkably stable. Thus, Na+/K+-ATPase function previously reported as altered by oxidative stress is not through induced changes in the expression of pump isoforms.
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Aberrant depressive-like behaviors in olfactory bulbectomized (OBX) mice have been documented by previous studies. Here, we show that memantine enhances adult neurogenesis in the subgranular zone of the hippocampal dentate gyrus (DG) and improves depressive-like behaviors via inhibition of the ATP-sensitive potassium (KATP) channel in OBX mice. Treatment with memantine (1-3 mg/kg; per os (p.o.)) for 14 days significantly improved depressive-like behaviors in OBX mice, as assessed using the tail-suspension and forced-swim tests. ⋯ In contrast, both the improvement of depressive-like behaviors and increase in BrdU-positive neurons in the DG following treatment with memantine were unapparent in OBX-treated Kir6.1 heterozygous (+/-) mice but not OBX-treated Kir6.2 heterozygous (+/-) mice. Furthermore, the increase in CaMKIV (Thr-196) and Akt (Ser-473) phosphorylation and BDNF protein expression levels was not observed in OBX-treated Kir6.1 +/- mice. Overall, our study shows that memantine improves OBX-induced depressive-like behaviors by increasing adult neurogenesis in the DG via Kir6.1 channel inhibition.
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A goal in addiction research is to distinguish forms of neuroplasticity that are involved in the transition to addiction from those involved in mere drug taking. Animal models of drug self-administration are essential in this context. Here, we compared in male rats two cocaine self-administration procedures that differ in the extent to which they evoke addiction-like behaviours. ⋯ Compared to LgA-90 s rats, IntA-5 s rats had more cocaine-induced c-fos mRNA in the orbitofrontal and prelimbic cortices and the caudate-putamen. Thus, a cocaine self-administration procedure (intermittent intake of rapid infusions) that promotes increased incentive motivation for the drug also enhances cocaine-induced gene regulation in corticostriatal regions. This suggests that increased drug-induced recruitment of these regions could contribute to the neural and behavioural plasticity underlying the transition to addiction.
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The cerebellar cognitive affective syndrome may result from various cerebellar injuries. Although it is not exactly known which anatomical structures are involved, the fastigial nucleus has been thought to play a pivotal role according to recent studies. Here we investigate whether bilateral fastigial nucleus lesions in juvenile rats affect cognitive-associative and limbic related functions in adulthood. ⋯ Furthermore, in the elevated plus maze anxiety was enhanced, whereas social behavior was not affected. Electrophysiological recordings showed enhanced local field coherence between mPFC and SMCtx across all frequency bands. Impaired cognitive and affective functions together with enhanced coherence between mPFC and SMCtx after bilateral fastigial nucleus lesions indicate that the fastigial nucleus contribute to the development of the cerebellar cognitive affective syndrome and associated motor behavior.
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The evidences from various studies show the association of peripheral and neuronal inflammation with complex pathophysiology of status epilepticus (SE). In this view, the present work attempted to develop a model of neuronal inflammation mediated SE by combining both epileptic and inflammatory components of the disease and also to mimic SE co-morbid with systemic inflammation by peripheral administration of the lipopolysaccharide (LPS) 2 h prior to the pilocarpine (PILO) induction in C57BL/6 mice. We evaluated the anti-convulsant and neuroprotective effects of 7-day prophylactic treatment with three conventional anti-epileptic drugs (Sodium valproate, SVP 300 mg/kg p.o.; Carbamazepine CBZ 100 mg/kg p.o.; Levetiracetam; LEV 200 mg/kg p.o.) of widespread clinical use. ⋯ Also, the decreased cytokine levels by the AEDs showed their association with NF-κB, IL-1β, IL-6, TNF-α and TGF-β pathways in PILO model. The loss of protective activities of SVP and CBZ in LPS+PILO model was due to increased cytokine levels associated with over-activation of neuroinflammatory pathways, however, partial efficacy of LEV is possibly due to association of other neuroinflammatory mechanisms. The current work provides direct evidence of the contribution of increased peripheral and neuronal inflammation in seizures via regulation of inflammatory pathways in the brain.