The roles of GluN3-containing N-methyl-D-aspartate receptor in central nerve system / 浙江大学学报·医学版

The N-methyl-D-aspartate receptor (NMDAR) in central nerve system is mostly composed of GluN1 and GluN2 subunits. The classical NMDAR has been intensively studied. However, GluN3‑containing NMDAR is much less expressed and have atypical channel properties. Recently, accumulating evidences have revealed two types of GluN3‑containing NMDAR: glutamate-gated GluN1/GluN2/GluN3 NMDAR and glycine-gated GluN1/GluN3 NMDAR. The former may play important roles in regulating synapse maturation and pruning non-used synapses, and its elevated expression at the adult stage may alter synaptic reorganization in some neuropsychiatric disorders. The latter is expressed in the medial habenula and involves in control of aversion. This article reviews the recent progresses on the expression, functional properties of GluN3‑containing atypical NMDARs and the physiological and pathological relevance.

Synaptic pruning mediated by glia in Alzheimer's disease / 药学学报

Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive impairment. To date, however, no disease-modifying strategies to prevent or cure AD exist. Synapses are involved in the connection of neurons and present as the key component for the memory and other neural activities. Synapse loss is a critical hallmark of AD pathology. In brain, glia cells, including microglia and astrocytes, are a group of highly specific cell types other than neurons. Microglia and astrocytes play a key role in maintaining the healthy neural circuit and regulating synaptic plasticity. Under development and physiological conditions, glial cells contribute to construct and maintain mature central neural networks via synaptic pruning. However, during AD pathogenesis, glial cells engulf synapses excessively, which leads to synapse loss, neuronal dysfunction, and cognitive impairment. Here, we review recent advances in our understanding of the underlying mechanisms for glia-mediated synaptic pruning in AD, and provide a novel strategy for the development of AD drugs.

Ketamine exhibit antidepressant effect through regulating sleep-wake rhythm and synaptic homeosta-sis / 中华行为医学与脑科学杂志

A single infusion of ketamine has sustained antidepressant effects and significantly de-creases the risk of suicide,and the effects can last up for 7-10 days,but the underlying mechanism is un-clear. The mechanism was reviewed underlying the antidepressant effects of ketamine,and found that ket-amine may exert its antidepressant effect by regulating sleep/wake cycle,synaptic pruning,molecular path-ways,and neural circuits for treatment-refractory depression. Further studies are needed to investigate the ge-netic,molecular mechanisms underlying the sustained antidepressant effect of ketamine,and the associated imaging findings through in vivo imaging of animals and imaging genetics techniques,explore the optimal time for administration of ketamine,and then provide accurate scientific basis for enhancing its anti-depressant effect.

Microglia and synaptic pruning in developmental brain / 中国病理生理杂志

Microglia, the main innate immune cells in the central nervous system, takes part in lots of physiological and pathological processes in the brain.It not only maintains brain homeostasis but also participates in the process of brain injury and repair under pathological conditions.In developmental brain, microglial synaptic pruning may eliminate weaker synapses and retain stronger synapses.Synaptic pruning also plays a vital role in mediating the formation of neural circuit under physiological condition, contributes to cell and myelin debris clearance, promotes maturation of oligodendrocytes, which surround the bare axon to form myelin sheath, and helps the regeneration of neurons and synapses.Recently, increasing number of studies on microglial synaptic pruning has advanced our understanding of the underlying mechanism for synaptic pruning and its relevant physiological functions.Here, we reviewed microglial synaptic pruning function and its potential regulatory mechanisms in brain under physiological and pathological conditions.