Neuroscience
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Amyloid β (Aβ) is a pathogenic peptide associated with many neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The retinal inflammation in response to Aβ is implicated in the pathogenesis of several ocular diseases including age-related macular degeneration, Alzheimer's-related optic neuropathy and glaucoma. In the present study, we found that a single intravitreal injection of oligomeric Aβ1-40 in mouse activated the NLRP3 inflammasome and the NF-κB signaling, induced the production of inflammatory cytokines including TNF-α and IL-6. ⋯ TO90 preserved ERG a- and b-wave amplitudes and reduced the number of Iba1-positive cells in the Aβ1-40-treated retina. Furthermore, TO90 down-regulated the mRNA levels of TNF-α and IL-6, as well as the expressions of p-IκBα, NLRP3, caspase-1 and IL-1β in the Aβ1-40-injected animals. We suggest that activation of LXRα and its target gene ABCA1 exerts potent anti-inflammatory effect on the Aβ-treated retina.
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Prenatal hypoxia induced by transient intrauterine ischemia is a serious clinical problem, and at present, effective treatments are lacking. Currently, it is unknown how prenatal hypoxia affects behaviors in adulthood. Therefore, we developed a mouse model that mimics prenatal hypoxia in humans using uterine artery occlusion in late gestation. ⋯ Neurochemical analysis revealed that dopamine was increased in the female hippocampus, but not in males. Thus, neonatal SSRI treatment decreases dopamine levels in the hippocampus in females selectively. Our findings suggest that prenatal hypoxia is a risk factor for behavioral abnormalities in adulthood, and that neonatal SSRI treatment might have clinical potential for alleviating these long-term behavioral deficits.
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Global cerebral ischemia and reperfusion injury (GCI/R) can lead to neuronal apoptosis and contributes to permanent neurological sequelae. However, the underlying mechanism is largely unknown. Therefore, the present study aimed to assess the effects of GCI/R on the tribbles homolog 3 (TRB3) and to explore the role of TRB3 in GCI/R. ⋯ These data implied that TRB3 participated in the GCI/R-induced neuronal apoptosis. Knocking down TRB3 attenuated endoplasmic reticulum stress, enhanced Akt phosphorylation, and protected neurons from apoptosis in response to GCI/R. These results demonstrated that the downregulation of TRB3 may be a promising approach for treating GCI/R.
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The injection of safe doses of botulinum neurotoxin A (BoNT/A) have been reported to be useful for the treatment of neuropathic pain, but it is still unknown how functional recovery is induced after peripheral nerve injury. We evaluated the effects of intranerve application of BoNT/A, on regeneration and sensorimotor functional recovery in partial and complete peripheral nerve injuries in the mouse. After sciatic nerve crush (SNC) and intranerve delivery of BoNT/A (15pg), axonal regeneration was measured by nerve pinch test at different days. ⋯ We observed also a higher expression of S100 in the distal portion of BoNT/A-injected regenerated nerves. In CCI mice, BoNT/A induced an increase in reinnervation of gastrocnemius and plantar muscles. These results show that a low dose of BoNT/A, insufficient to produce muscular dysfunction, conversely speeds up sensorimotor recovery by stimulating myelinated axonal regeneration, and points out its application as a multipotent treatment for peripheral neuropathies.
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Aquaporin-4 (AQP4) is the predominant water channel in mammalian CNS where it is localized at the perivascular astrocytic foot processes abutting brain microvessels. Several lines of evidence suggest that AQP4 is involved in important homeostatic functions and that mislocalization of the perivascular pool of AQP4 is implicated in several different brain disorders. A recent study suggests that the differential susceptibility of midbrain dopaminergic neurons to the parkinsonogenic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) depends on the expression of AQP4. ⋯ Treatment with MPTP further increased (by >30%) the perivascular AQP4 density in SN, but also increased AQP4 labeling in the neocortex. Our data indicate that the perivascular AQP4 pool in SN is high in normal animals and even higher after treatment with MPTP. This would leave the SN more prone to water accumulation and supports the idea that AQP4 could be involved in the pathogenesis of PD.