Role of vascular endothelial growth factor as a critical neurotrophic factor for the survival and physiology of motoneurons

Vascular endothelial growth factor(VEGF)was discovered by its angiogenic activity.However,during evolution,it appeared earlier as a neurotrophic factor required for the development of the nervous system in invertebrates lacking a circulatory system.We aimed at reviewing recent evidence indicating that VEGF has neuroprotective effects in neurons exposed to a variety of insults.Of particular interest is the link established between VEGF and motoneurons,especially after the design of the VEGFδ/δmutant mice.These mice are characterized by low levels of VEGF and develop muscle weakness and motoneuron degeneration resembling amyotrophic lateral sclerosis.The administration of VEGF through several routes to animal models of amyotrophic lateral sclerosis delays motor impairment and motoneuron degeneration and increases life expectancy.There are new recent advances in the role of VEGF in the physiology of motoneurons.Our experimental aims use the extraocular(abducens)motoneurons lesioned by axotomy as a model for studying VEGF actions.Axotomized abducens motoneurons exhibit severe alterations in their discharge activity and a loss of synaptic boutons.The exogenous administration of VEGF to axotomized abducens motoneurons,either from the transected nerve or intraventricularly,fully restores the synaptic and discharge properties of abducens motoneurons,despite being axotomized.In addition,when an anti-VEGF neutralizing antibody is delivered from the muscle to intact,uninjured abducens motoneurons,these cells display alterations in their discharge pattern and a loss of synaptic boutons that resemble the state of axotomy.All these data indicate that VEGF is an essential neurotrophic factor for motoneurons.

Bioinformatics and system biology approach to identify influences of BDNF on depression model

OBJECTIVE The classic animal model of depression is CUMS,and one of the hypotheses is related to the decrease of brain-de⁃rived neurotrophic factor(BNDF)expression in the brain,and its corresponding animal model is BDNF knockdown mice.BDNF can promote neu⁃ronal differentiation,maintain neuronal growth,and repair neuronal damage.The reduction of BDNF is related to the severity of depression.In contrast,the deletion of IDO-1 could promote the maintain the homeostasis of neurotransmitters in the brain.Therefore,the construction of BDNF and IDO-1 models for sequencing comparison can reveal the neurotransmitter hypothesis of de⁃pression from the transcriptome level.METH⁃ODS In order to obtain its transcriptome expres⁃sion profile,firstly construct BDNF knockdown,IDO-1 knockout and CUMS model.The differen⁃tial expression of mRNAs was done by sequenc⁃ing provider BGI,conducting R for analyze.Clus⁃terproflier was used to enrich GO and KEGG pathway annotations.The ceRNA package was used search database LncRNA2Target to dig potential lncRNAs.Finally,the Stringdb was used to construct the PPI network.RESULTS We identified a large number of mRNAs in mice normal and depression-like tissues from diverse genomic locations,and these mRNAs were col⁃lected from medial prefrontal cortex(mPFC)manner.Based on the analysis of the enrichment pathway and ceRNA network,we found numer⁃ous abundant mRNAs are specifically expressed in gene editing group,and differentially expressed in depression-like compared with normal tissues or depression-like antagonism group.Indicates that they serve a specific function in specific pathways.We focused on the mPFC sequencing of gene modification mice especially in BDNF+/-and IDO-/-.There is a relatively large difference in expression matrix.Certain mRNA,like Ptbp1,are predominantly expressed in comparison of BDNF+/-and other groups,and present at sub⁃stantial levels,that suggest these mRNAs are purposefully produced.Furtherly analysis of cor⁃relation map,Ptbp1 are related to the protection of vulnerable neuronal circuits and pathways are clustered in nervous system development and synapse organization.CONCLUSION We described the potential enrichment DEGs and its pathway in three model mice related to depres⁃sion.We propose gene regulation by the ceRNA network in the progression of depression mod⁃els,which could help in revealing the new mech⁃anisms and understranding of neurotransmitter hypothesis of depression.

Retinal pigment epithelial cells:biological property and application in Parkinson's disease

Parkinson＇s disease is a neurodegenerative disorder mainly caused by degeneration of the dopaminergic neurons in the substantia nigral pars compacta （SNpc）. The typical motor symptoms of this disease are tremor, akinesia, and rigidity, which are mostly caused by dysfunction of the nigro-striatal pathway. Dopaminergic neurons in the SNpc project long axons to caudate nucleus and the putamen, and secrete dopamine.