Neuroscience
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Several studies in rodents have shown that dysfunctions of the thalamic reticular nucleus (TRN) result in deficits of sensory gating and attentional processes, two core features of schizophrenia. TRN receives inputs from the prefrontal cortex (PFC) and hippocampal formation, two structures which send excitatory projections to the nucleus accumbens (NAcc) and are interconnected with the basolateral amygdala (BLA). Here we determined whether (and which) changes occurred four weeks after a TRN lesion in the dendritic morphology of pyramidal neurons of layers 3 and 5 of the PFC, neurons of ventral and dorsal hippocampus, BLA, and the medium spiny neurons of the NAcc. ⋯ We also evaluated the effects of TRN lesion on exploratory behavior assessed by hole-board test and locomotor activity induced by a novel environment. We found that TRN damage induced a reduction in the exploratory behavior measured by hole-board test with neuronal hypotrophy in PFC (layer 5), CA1 ventral hippocampus and NAcc neurons. Taken together, these data suggest that the behavioral and morphological effects of TRN lesion are, at least partially, mediated by limbic subregions with possible consequences for schizophrenia-related behaviors.
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Maternal separation (MS) during the first postnatal weeks induces alcohol intake and a reduction in the expression of glucocorticoid receptors (GR). Adults' alcohol consumption may depend on changes in the endocannabinoid system (eCBs). Our goal was to evaluate the status of the eCBs before the exposition to alcohol to support the notion that eCBs' alterations prompt rats to drink alcohol. ⋯ We found GABA levels increased in FCx and HIP but decreased in VS in MS. Likewise, glutamate levels increased in the FCx but decreased in the HIP in MS subjects. These findings suggest that MS induces changes in the CB1R expression, which might contribute to induce a proclivity to ingest alcohol and, potentially, other drugs.
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Traumatic Brain injury affects at least 1.7 million people in the United States alone each year. The majority of injuries are categorized as mild but these still produce lasting symptoms that plague the patient and the medical field. Currently treatments are aimed at reducing a patient's symptoms, but there is no effective method to combat the source of the problem, neuronal loss. ⋯ Since the protective stress response molecule, HSP70, can be upregulated by Nrf2, we examined protein levels in the hippocampus, and found that HSP70 was elevated by the injury and then further increased by the treatment. To test the possible role of HSP70, model neurons in culture exposed to a mild injury and treated with the Nrf2 activator displayed improved survival that was blocked by the HSP70 inhibitor, VER155008. Following mild traumatic brain injury, there may be a partial protective response and patients could benefit from directed enhancement of regulatory pathways such as Nrf2 for neuroprotection.
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The present study investigated the effects of a microinjection of GABA(A) receptor agonist (muscimol) and antagonist (bicuculline) into the central nucleus of the amygdala (CeA) in sodium-depleted rats. We measured the sodium intake and identified the neuronal activation in the brainstem induced by activating the GABA(A) receptors in the CeA using Fos immunohistochemistry. Muscimol (0.20, 0.35 or 0.50 nmol, in 0.2μl) that was injected bilaterally into the CeA decreased the 0.3M NaCl and water intake in a dose-dependent manner. ⋯ However, bilateral injections of bicuculline alone into the CeA did not affect the NaCl or water intake. Furthermore, microinjection of muscimol (0.20 nmol) into the CeA increased the number of Fos-like immunoreactive (FLI) neurons in the caudal and intermediate parts of the nucleus of the tractus solitarius (cNTS and iNTS) and the lateral parabrachial nucleus (LPBN). These results suggest that GABA(A) receptors within the CeA may be involved in mediating the sodium intake in the sodium-depleted rat, and the cNTS, iNTS and LPBN were probably involved in this mechanism.
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Transplantation of bone marrow stromal cells (BMSCs) is a potential therapy for ischemic stroke, but poor environmental conditions in brain lesions, such as insufficient nutrition and oxygen free radical toxicity, limit the efficacy of stem cell therapy. Here, we hypothesized that MCI-186, a free radical scavenger, would have protective effects on transplantation of BMSCs in a rat ischemia model. In vitro, flow cytometry showed the apoptotic rates of BMSCs after simulated ischemia-reperfusion (I/R) injury was significantly decreased when treated with MCI-186 (P<0.01). ⋯ When compared with BMSCs or MCI-186 monotherapy, combination therapy significantly improved functional restoration, decreased infarct volume, and increased the number of engrafted-BMSCs and neurons in ischemic brain. The number of engrafted-BMSCs and neurons was significantly correlated with functional outcomes. This study suggests that MCI-186 may improve the environment of the injured brain, enhance the survival of engrafted-BMSCs and neurotization in ischemic brain and produce protective effects on BMSCs transplantation.