Neuroscience
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The pancreatic peptide, Amylin (AMY), reportedly affects nociception in rodents. Here, we investigated the potential effect of AMY on the tolerance to morphine and on the expression of BDNF at both levels of protein and RNA in the lumbar spinal cord of morphine tolerant rats. Animals in both groups of control and test received a single daily dose of intrathecal (i.t.) morphine for 10 days. ⋯ Levels of pro-BDNF and BDNF proteins remained unchanged in the lumbar spinal cord of rats treated by AMY alone. These results suggest that i.t. AMY not only abolished morphine tolerance, but also reduced the morphine induced increase in the expression of both BDNF transcripts and protein in the lumbar spinal cord.
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Schwann cells (SCs) combined with acellular nerve allografts (ANAs) effectively promote the regeneration and repair of peripheral nerves, but the exact mechanism has not been fully elucidated. However, the disadvantages of SCs include their limited source and slow rate of expansion in vitro. Previous studies have found that adipose-derived stem cells have the ability to differentiate into Schwann-like cells. ⋯ The results showed that adipose-derived Schwann-like cells combined with ANAs markedly promoted sciatic nerve regeneration and repair. These findings also demonstrated that the expression of neurotrophic factors (NFs) was increased, and the expression of Janus activated kinase2 (JAK2)/P-JAK2, signal transducer and activator of transcription-3 (STAT3)/P-STAT3 was decreased in the spinal cord after SNI. Therefore, these results suggested that highly expressed NFs in the spinal cord could promote nerve regeneration and repair by inhibiting activation of the JAK2/STAT3 signaling pathway.
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Growing evidence indicates that early-life inflammation has adverse effects on adult hippocampal neurogenesis and GABA system. Based the report that hippocampal GABA system is a key modulator in adult hippocampal neurogenesis, the aim of this study was to investigate whether and how early inflammation affects GABAergic system resulting in the alterations of adult hippocampal neurogenesis and related behaviors. Neonatal mice received a daily subcutaneous injection of lipopolysaccharide (LPS, 50 μg/kg) or saline on postnatal days (PND) 3-5. ⋯ Additionally, postnatal LPS treatment resulted in the activation of astrocytes and the increase expression of toll-like receptor 4 (TLR4) in the second postnatal week and the downregulation of BDNF-TrkB pathway in adulthood. The treatment with TLR4 inhibitor TAK-242 restored the decrease of BrdU+/NeuN+ cells and depression-like behaviors in LPS mice via improving GABAAR. The results indicate that postnatal LPS exposure impairs adult hippocampal neurogenesis and causes depression-like behaviors through early astrocytes activation triggering the later GABAAR downregulation.
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An important pathology in Parkinson's disease (PD) is the earlier and more severe degeneration of noradrenergic neurons in the locus coeruleus (LC) than dopaminergic neurons in the substantia nigra. However, the basis of such selective vulnerability to insults remains obscure. Using noradrenergic and dopaminergic cell lines, as well as primary neuronal cultures from rat LC and ventral mesencephalon (VM), the present study compared oxidative DNA damage response markers after exposure of these cells to hydrogen peroxide (H2O2). ⋯ Consistent with these measurements, exposure of SK-N-BE(2)-M17 cells to H2O2 resulted in higher levels of reactive oxygen species (ROS). Further experiments showed that exposure of SK-N-BE(2)-M17 cells to H2O2 caused an increased level of noradrenergic transporter, reduced protein levels of copper transporter (Ctr1) and 8-oxoGua DNA glycosylase, as well as amplified levels of Cav1.2 and Cav1.3 expression. Taken together, these experiments indicated that noradrenergic neuronal cells seem to be more vulnerable to oxidative damage than dopaminergic neurons, which may be related to the intrinsic characteristics of noradrenergic neuronal cells.
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Microglia activation plays a key role in regulating inflammatory and immune reaction during cerebral ischemia and it exerts pro-inflammatory or anti-inflammatory effect depending on M1/M2 polarization phenotype. Cysteinyl leukotriene 2 receptor (CysLT2R) is a potent inflammatory mediator receptor, and involved in cerebral ischemic injury, but the mechanism of CysLT2R regulating inflammation and neuron damage remains unclear. Here, we found that LPS and CysLT2R agonist NMLTC4 significantly increased microglia proliferation and phagocytosis, up-regulated the mRNA expression of M1 polarization markers (IL-1β, TNF-α, IFN-γ, CD86 and iNOS), down-regulated the expression of M2 polarization markers (Arg-1, CD206, TGF-β, IL-10, Ym-1) and increased the release of IL-1β and TNF-α. ⋯ The conditional medium of BV-2 cells contained HAMI3379 could inhibit SH-SY5Y cells apoptosis induced by LPS and NMLTC4. These results were further confirmed in primary microglia. The findings indicate that CysLT2R was involved in inflammation and neuronal damage by inducing the activation of microglia M1 polarization and NF-κB pathway, inhibiting microglia M1 polarization and promoting microglia polarization toward M2 phenotype which may exerts neuroprotective effects, and targeting CysLT2R may be a new therapeutic strategy against cerebral ischemia stroke.