Neuroscience
-
Intraventricular hemorrhage (IVH) is a frequent complication of preterm newborns, resulting in cerebral palsy and cognitive handicap as well as hypoxic ischemic encephalopathy and periventricular leukomalacia. In this study, we investigated the restorative effect on neonatal IVH by umbilical cord-derived mesenchymal stromal cells (UC-MSCs) cultured in serum-free medium (RM medium) for clinical application. UC-MSCs were cultured with αMEM medium supplemented with FBS or RM. ⋯ Histopathological analysis revealed UC-MSCs cultured with RM significantly attenuated periventricular reactive gliosis, hypomyelination, and periventricular cell death observed after IVH. Furthermore, human brain-derived neurotrophic factor and hepatocyte growth factor were elevated in the serum, cerebrospinal fluid and brain tissue of neonatal IVH model mice 24h after UC-MSCs administration. These results suggest UC-MSCs attenuate neonatal IVH by protecting gliosis and apoptosis of the injured brain, and intravenous injection of UC-MSCs cultured in RM may be feasible for neonatal IVH in clinic.
-
Brain developmental disorders such as lissencephaly can result from faulty neuronal migration and differentiation during the formation of the mammalian neocortex. The cerebral cortex is a modular structure, where developmentally, newborn neurons are generated as a neuro-epithelial sheet and subsequently differentiate, migrate and organize into their final positions in the cerebral cortical plate via a process involving both tangential and radial migration. The specific role of Mest, an imprinted gene, in neuronal migration has not been previously studied. ⋯ The differentiation and migration properties of neurons via Wnt-Akt signaling were affected by Mest changes. In addition, miR-335, encoded in a Mest gene intron, was identified as being responsible for blocking the default tangential migration of the neurons. Our results suggest that Mest and its intron product, miR-335, play important roles in neuronal migration with Mest regulating the morphological transition of primary neurons required in the formation of the mammalian neocortex.
-
Dopamine (DA), an important neurotransmitter and neuromodulator, plays important roles in neuronal physiological functions by activating G-protein-coupled DA D1 and/or D2 receptors. Previous studies have demonstrated that D1 receptors are functionally expressed in retinal neurons and glial cells, including ganglion cells. In this study, we explored the effects of D1 receptor activation on retinal ganglion cell (RGC) temporal summation and excitability in rat retinal slices using electrophysiological techniques. ⋯ Additionally, SKF81297 increased the spontaneous firing frequency of RGCs, and caused depolarization of the cells with or without the presence of synaptic receptor blockers. In contrast, SKF81297 did not significantly change the frequency of miniature excitatory postsynaptic currents (mEPSCs) recorded in RGCs. Our results indicate that D1 receptor activation enhances the temporal summation of RGCs mainly by suppressing Kir currents through the cAMP/PKA signaling pathway, thus increasing the excitability of rat RGCs.
-
Perineuronal nets (PNNs) are structures of extracellular matrix molecules surrounding the cell bodies and proximal dendrites of certain neurons. While PNNs are present throughout the mouse cerebral cortex, recent studies have shown that the components differ among cortical sub-regions and layers, suggesting region-specific functions. Parvalbumin-expressing interneurons (PV neurons) may be important regulators of cortical plasticity during the early "critical period" that is sensitive to sensory input. ⋯ These WFA(+) PNNs changed from granular-like to reticular-like structures during normal cortical development, while this transition was delayed by sensory deprivation. This study indicates that the formation of reticular-like WFA(+) PNNs is dependent on sensory experience in the mouse somatosensory cortex. We suggest that Cat-315(+) molecules and WFA expression in PNNs are involved in the early critical period of input-dependent cortical plasticity.
-
Chitinase activity is increased in Alzheimer's disease (AD). However, the role of chitinase1 in AD is unknown. We investigated the effects of chitinase1 on Alzheimer's pathology and microglia function. ⋯ A higher level of M2 markers (Arg-1, MRC1/CD206) and a lower level of classic M1 markers (TNFa, IL-1β) were obtained in Aβ-pretreated N9 cells with chitinase1, suggesting that chitinase1 polarized the microglia into an anti-AD M2 phenotype. We also detected that chitnase1 could weaken the deposition of Aβ oligomers in the brain of D-galactose/ AlCl3-induced AD rats. In conclusion, Chitinase1 might exert protective effects against AD by polarizing microglia to an M2 phenotype and resisting Aβ oligomer deposition.