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Use of a Caspase Multiplexing Assay to Determine Apoptosis in a Hypothalamic Cell Model
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Use of a Caspase Multiplexing Assay to Determine Apoptosis in a Hypothalamic Cell Model

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Reduced Hippocampal Neurogenesis in Mice Deficient in Apoptosis Repressor with Caspase Recruitment Domain (ARC)

Golo Kronenberg1, Karen Gertz2, Ria Uhlemann2

  • 1University of Leicester and Leicestershire Partnership NHS Trust, Leicester, United Kingdom.

Neuroscience
|July 30, 2019
PubMed

Insights

The apoptosis repressor with caspase recruitment domain (ARC) is crucial for new neuron survival in the adult hippocampus. ARC deficiency reduces new granule cell neuron development and survival, highlighting its role in neurogenesis.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Adult hippocampal neurogenesis is vital for learning and memory.
  • Newly generated neurons in the dentate gyrus are susceptible to apoptosis.
  • The apoptosis repressor with caspase recruitment domain (ARC) inhibits cell death pathways.

Purpose of the Study:

  • To investigate the role of ARC in adult hippocampal neurogenesis.
  • To determine if ARC influences the proliferation, survival, and differentiation of new neurons.

Main Methods:

  • In situ hybridization to detect Nol3 gene expression.
  • Flow cytometry (FACS) of neural stem cells and immature neurons.
  • Analysis of ARC-deficient (ARC-/-) mice using BrdU labeling.
  • Immunohistochemistry for Doublecortin (DCX) and calretinin (CR) positive cells.
  • Assessment of microglia activation and BDNF protein levels.

Main Results:

  • Nol3 gene expression is upregulated during adult neurogenesis.
  • ARC deficiency significantly reduces the proliferation and survival of new neurons.
  • The number of immature neurons (DCX+) and postmitotic neurons (CR+) is decreased in ARC-/- mice.
  • Neuronal-glial fate choice remains unaffected by ARC deficiency.
  • Increased hippocampal BDNF levels observed in ARC-/- mice, suggesting a compensatory mechanism.

Conclusions:

  • ARC plays a critical cell-autonomous role in promoting the survival of new neurons during adult hippocampal neurogenesis.
  • ARC is essential for maintaining the pool of newly generated granule cells.
  • ARC deficiency impacts neurogenesis without affecting neuronal-glial fate determination or causing glial activation.
Keywords:
ARCBDNFadult hippocampal neurogenesisapoptosismicroglia

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