Neuroscience
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Oscillating field stimulation (OFS) has been used in attempts to treat spinal cord injury (SCI) and has been shown to improve remyelination after SCI in rats. However, some controversies regarding the effects of OFS have been presented in previous papers. Oligodendrocytes (OLs) are the main cell for remyelination and are derived from the differentiation of oligodendrocyte precursor cells (OPCs). ⋯ Our results showed a significant improvement in the differentiation of OPCs and the content of ATP and LIF in the injured spinal cord in the OFS group. Furthermore, BBB scores and tcMMEPs were significantly improved in the rats stimulated by OFS. These findings suggest that OFS can improve the differentiation of OPCs and promote the recovery of neurological function following SCI in rats.
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Increased understanding of the neurovascular niche suggests that development of the central nervous system (CNS) and its vasculature is coordinated through shared regulatory factors. These include the vascular endothelial growth factor (VEGF) family, reported to promote neuroproliferation and neuroprotection in addition to angiogenesis via its receptors VEGFR1-3. VEGFR3, a mediator of lymphangiogenesis, is expressed in murine and rat brain from early gestation, has been associated with neural progenitors and neurons (Choi et al., 2010) and oligodendroglia (Le Bras et al., 2006) in the developing cortex and is reported to mediate adult neurogenesis in the subventricular zone (SVZ) (Calvo et al., 2011). ⋯ High expression in ventricular ependyma, choroid plexus and pigmented retinal epithelium was noted from E18. VEGFC ligand was found in association with VEGFR3 throughout development, with highest expression in embryonic stages. Our findings suggest an important role for VEGFC/VEGFR3 signaling in neuronal proliferation in early forebrain development, and ongoing functions with niche neurogenesis, glial and ependymal function in the maturing postnatal brain.
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Damage to the cholinergic input to the prefrontal cortex has been implicated in neuropsychiatric disorders. Cholinergic endings release acetylcholine, which activates nicotinic and/or G-protein-coupled muscarinic receptors. Muscarinic receptors activate transduction systems, which control cellular effectors that regulate the membrane potential in medial prefrontal cortex (mPFC) neurons. ⋯ CCh-dependent depolarization was abolished in the presence of antibodies against Nav1.9 channels in the intracellular solution and augmented by the presence of ProTx-I toxin (100 nM) in the extracellular solution. CCh-induced depolarization was not affected by the following reagents: intracellular transduction system blockers, including U-73122 (10 μM), chelerythrine chloride (5 μM), SQ 22536 (100 μM) and H-89 (2 μM); channel blockers, including Ba(++) ions (200 μM), apamin (100 nM), flufenamic acid (200 μM), 2-APB (200 μM), SKF 96365 (50 μM), and ZD 7288 (50 μM); and a Na(+)/Ca(++) exchanger blocker, benzamil (20 μM). We conclude that muscarinic M1 receptor-dependent depolarization in mPFC pyramidal neurons is evoked by the activation of Nav1.9 channels and that the signal transduction pathway involves G-protein βγ subunits.
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Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder with increased oxidative stress, the underlying vital process contributing to cell death. Tanshinone IIA (Tan IIA), a major bioactive diterpene quinone of Salva miltiorrhiza, had been proved effective in the MPTP model through its anti-inflammatory activity. Here in this research, we found that Tan IIA prevented the loss of nigrostriatal dopaminergic neurons by activating the NF-E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway. ⋯ Further studies revealed that Tan IIA reduced the enhancement of miR-153 by 6-OHDA, which targeted the 3'-UTR of Nrf2, and suppressed its expression and activation. Additionally, neurodegeneration caused by in vivo stereotaxic injection of 6-OHDA could also be ameliorated by the administration of Tan IIA. Taken together, our results strongly suggest that Tan IIA may be beneficial for the treatment of PD, and also confirm that targeting the Nrf2/ARE pathway is a promising strategy for therapeutic intervention in PD.
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Fragile X syndrome (FXS) is an inherited neurodevelopmental disorder affecting nearly one in 5000 newborn males and is a leading genetic cause of autism spectrum disorder. In addition to developmental delays and intellectual impairment, FXS is characterized by seizures, attention deficit, and hypersensitivity to visual, tactile and auditory stimuli. The Fmr1 gene encodes Fragile X mental retardation protein (FMRP), which is abundant in neurons, binds select mRNAs and functions as a negative regulator of mRNA translation. ⋯ Additionally, neurons in the medial superior olive (MSO) were more round in Fmr1 KO rats. There was also reduced expression of glutamic acid decarboxylase (GAD67) in neurons of the superior paraolivary nucleus (SPON) and a reduction in the number of calretinin-immunoreactive terminals associated with neurons of the medial nucleus of the trapezoid body (MNTB). Together, these findings support the conclusion that the auditory dysfunction characteristic of FXS arises, at least in part, from defective brainstem networks.