Neuroscience
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by synaptic loss and cognitive impairments. Although AD is the most prevalent aging-related neurodegenerative disease, therapeutic strategies remain palliative. Recent studies have shown that probucol presents neuroprotective effects in experimental models of neurodegenerative disease. ⋯ STZ infusions are able to increase hippocampal BACE expression. Moreover, the results also show that probucol can counteract STZ-induced cognitive impairments and biochemical parameters independently of potential modulator effects toward BACE levels. The study is the first to report the protective effects of probucol against STZ-induced biochemical hippocampal changes and behavioral impairments, rendering this compound a promising molecule for further pharmacological studies on the search for therapeutic strategies to treat or prevent AD.
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Cholinergic activation of the medial septal area (MSA) with carbachol produces thirst, natriuresis, antidiuresis and pressor response. In the brain, hydrogen peroxide (H2O2) modulates autonomic and behavioral responses. In the present study, we investigated the effects of the combination of carbachol and H2O2 injected into the MSA on water intake, renal excretion, cardiovascular responses and the activity of vasopressinergic and oxytocinergic neurons in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. ⋯ Combining H2O2 and carbachol into the MSA also reduced the number of vasopressinergic neurons expressing c-Fos in the PVN (46.4±11.2, vs. carbachol: 98.5±5.9 c-Fos/AVP cells) and oxytocinergic neurons expressing c-Fos in the PVN (38.5±16.1, vs. carbachol: 75.1±8.5 c-Fos/OT cells) and in the SON (57.8±10.2, vs. carbachol: 102.7±7.4 c-Fos/OT cells). Glibenclamide (K+ATP channel blocker) into the MSA partially reversed H2O2 inhibitory responses. These results suggest that H2O2 acting through K+ATP channels in the MSA attenuates responses induced by cholinergic activation in the same area.
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The effects of motilin on voltage-dependent K+ currents in hippocampal neurons with the addition of L-arginine (L-AA), D-arginine (D-AA) and N-nitro-L-arginine methyl ester (L-NAME) were investigated in this study. ⋯ The inhibiting effects of motilin on the voltage-dependent K+ current in hippocampal neurons indicate that motilin acts as a regulatory factor for the nitric oxide pathway.
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Several lines of evidence indicate that the dorsal hippocampus (dH) and medial prefrontal cortex (mPFC) regulate contextual fear conditioning. The prelimbic (PrL), infralimbic (IL) and the anterior cingulate cortex (ACC) subregions of the mPFC likely play distinct roles in the expression of fear. Moreover, studies have highlighted the role of serotonin (5-hydroxytryptamine, 5-HT)- and γ-aminobutyric acid (GABA)-mediated mechanisms in the modulation of innate fear in the mPFC. ⋯ The present results confirmed the involvement of PrL and Cg1 in the expression of FPS and freezing responses to aversive conditions. In addition, PrL serotoninergic mechanisms play a key role in contextual fear conditioning. This study suggests that PrL, IL and Cg1 distinctively contribute to the modulation of contextual fear conditioning.
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Early immature neuronal death initiates cerebral ischemia-induced neurogenesis in the dentate gyrus.
Throughout adulthood, neurons are continuously replaced by new cells in the dentate gyrus (DG) of the hippocampus, and this neurogenesis is increased by various neuronal injuries including ischemic stroke and seizure. While several mechanisms of this injury-induced neurogenesis have been elucidated, the initiation factor remains unclear. Here, we investigated which signal(s) trigger(s) ischemia-induced cell proliferation and neurogenesis in the hippocampal DG region. ⋯ Moreover, early immature neuronal death in the DG initiated transient forebrain ischemia/reperfusion-induced neurogenesis through glycogen synthase kinase-3β/β-catenin signaling, which was mediated by microglia-derived insulin-like growth factor-1 (IGF-1). Additionally, we observed that the blockade of immature neuronal cell death, early microglial activation, or IGF-1 signaling attenuated ischemia-induced neurogenesis. These results suggest that early immature neuronal cell death initiates ischemia-induced neurogenesis through microglial IGF-1 in mice.