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Endoplasmic reticulum stress contributes to CRH-induced hippocampal neuron apoptosis

Yue Zhang1, Wei Liu, Chunling Ma

  • 1Department of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China.

Experimental Cell Research
|January 31, 2012
PubMed

Insights

Corticotropin releasing hormone (CRH) induces hippocampal neuron apoptosis by activating endoplasmic reticulum (ER) stress. This ER stress response involves the IRE1/ASK1/JNK pathway, highlighting a novel mechanism in stress-induced neuronal cell death.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Endocrinology

Background:

  • The hypothalamic-pituitary-adrenal (HPA) axis regulates stress response.
  • Corticotropin releasing hormone (CRH) is a key regulator of the HPA axis.
  • CRH's role in stress-induced hippocampal neuron apoptosis requires further mechanistic elucidation.

Purpose of the Study:

  • To investigate the mechanisms underlying CRH-induced hippocampal neuron apoptosis.
  • To determine the involvement of endoplasmic reticulum (ER) stress in this process.

Main Methods:

  • In vitro assessment of hippocampal neuron viability after CRH treatment.
  • Measurement of ER stress markers (GRP78, CHOP, caspase-12) and signaling pathway components (IRE1, ASK1, JNK).
  • Inhibition of ER stress and specific pathways using chemical inhibitors (salubrinal, thioredoxin, SP600125) and assessment of apoptosis via flow cytometry.

Main Results:

  • CRH decreased hippocampal neuron viability in a dose- and time-dependent manner.
  • CRH upregulated ER stress markers (GRP78, CHOP, cleaved caspase-12) and activated the IRE1/ASK1/JNK signaling cascade.
  • Inhibiting ER stress or the IRE1/ASK1/JNK pathway attenuated CRH-induced apoptosis.

Conclusions:

  • Endoplasmic reticulum (ER) stress plays a critical role in CRH-induced hippocampal neuron apoptosis.
  • The IRE1/ASK1/JNK cascade is a key pathway mediating CRH-induced neuronal cell death.
  • CRH-induced apoptosis involves ER stress activation, offering potential therapeutic targets.

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