Dysregulation of neurogenesis by neuroinflammation:key differences in neurodevelopmental and neurological disorders

Embryonic neurogenesis is the process of generating neurons,the functional units of the brain.Because of its sensitivity to adverse intrauterine environment such as infection,dysregulation of this process has emerged as a key mechanism underlying many neurodevelopmental disorders such as autism spectrum disorders（ASD）.Adult neurogenesis,although is restricted to a few neurogenic niches,plays pivotal roles in brain plasticity and repair.Increasing evidence suggests that impairments in adult neurogenesis are involved in major neurodegenerative disorders such as Alzheimer＇s disease.A hallmark feature of these brain disorders is neuroinflammation,which can either promote or inhibit neurogenesis depending upon the context of brain microenvironment.In this review paper,we present evidence from both experimental and human studies to show a complex picture of relationship between these two events,and discussed potential factors contributing to different or even opposing actions of neuroinflammation on neurogenesis in neurodevelopmental and neurological disorders.

The Role of MicroRNAs in Neural Stem Cells and Neurogenesis

Neural stem cells give rise to neurons through the process of neurogenesis, which includes neural stem cell proliferation, fate deter- mination of new neurons, as well as the new neuron＇s migration, maturation and integration. Currently, neurogenesis is divided into two phases： embryonic and adult phases. Embryonic neurogenesis occurs at high levels to form the central nervous system. Adult neurogenesis has been consistently identified only in restricted regions and occurs at low levels. As the basic process for embryonic neurodevelopment and adult brain maintenance, neurogenesis is tightly regulated by many factors and pathways. MicroRNA, short non-coding RNA that regulates gene expression at the post-transcriptional level, appears to be involved in multiple steps of neurogenesis. This review summarizes the emerging role of microRNAs in regulating embryonic and adult neurogenesis, with a particular emphasis on the proliferation and differentiation of neural stem cells.

CXCR5 Regulates Neuronal Polarity Development and Migration in the Embryonic Stage via F‑Actin Homeostasis and Results in Epilepsy‑Related Behavior

Epilepsy is a common,chronic neurological disorder that has been associated with impaired neurodevelopment and immunity.The chemokine receptor CXCR5 is involved in seizures via an unknown mechanism.Here,we first determined the expression pattern and distribution of the CXCR5 gene in the mouse brain during different stages of development and the brain tissue of patients with epilepsy.Subsequently,we found that the knockdown of CXCR5 increased the susceptibility of mice to pentylenetetrazol-and kainic acid-induced seizures,whereas CXCR5 overexpression had the opposite effect.CXCR5 knockdown in mouse embryos via viral vector electrotransfer negatively influenced the motility and multipolar-to-bipolar transition of migratory neurons.Using a human-derived induced an in vitro multipotential stem cell neurodevelopmental model,we determined that CXCR5 regulates neuronal migration and polarization by stabilizing the actin cytoskeleton during various stages of neurodevelopment.Electrophysiological experiments demonstrated that the knockdown of CXCR5 induced neuronal hyperexcitability,resulting in an increased number of seizures.Finally,our results suggested that CXCR5 deficiency triggers seizure-related electrical activity through a previously unknown mechanism,namely,the disruption of neuronal polarity.