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Synaptic Elimination in Neurological Disorders.

Pablo L Cardozo1, Izabella B Q de Lima1, Esther M A Maciel1

  • 1Laboratório de Neurobioquímica, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Current Neuropharmacology
|June 5, 2019
PubMed
Summary
This summary is machine-generated.

Synaptic pruning, essential for brain wiring, can be disrupted by the complement system. Excessive pruning, mediated by microglia, may contribute to neurological disorders like Alzheimer's disease.

Keywords:
Synaptic eliminationalzheimer’s diseasecomplement cascademicrogliamultiple sclerosisschizophreniasynaptic plasticity.

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Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Synapses are crucial for neuronal communication, formed via synaptogenesis and eliminated via synaptic pruning.
  • Synaptic pruning refines neural circuits by removing weak synapses, guided by neuronal activity.
  • The classical complement cascade's role in promoting synaptic pruning is a recent discovery.

Purpose of the Study:

  • To review the role of the classical complement cascade in synaptic pruning.
  • To discuss the potential involvement of excessive synaptic elimination in Alzheimer's disease.
  • To explore links between aberrant synaptic pruning and other neurological disorders.

Main Methods:

  • Literature review focusing on synaptic pruning mechanisms.
  • Analysis of studies investigating complement component 3 (C3) and microglial involvement.
  • Examination of evidence for excessive pruning in neurological disease models.

Main Results:

  • Microglia engulf synapses tagged by complement component 3 (C3).
  • Disrupted synaptic pruning can lead to neural circuit alterations and neuropathology.
  • Evidence suggests excessive pruning in Alzheimer's disease models, involving C3 and microglia.

Conclusions:

  • The complement cascade, particularly C3, plays a key role in activity-dependent synaptic pruning via microglia.
  • Aberrant synaptic pruning may underlie neuropathological changes in Alzheimer's disease and potentially other neurological conditions like multiple sclerosis and schizophrenia.