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Effects of 5-h multimodal stress on the molecules and pathways involved in dendritic morphology and cognitive

Yiran Xu1, Xiaorui Cheng1, Xiuliang Cui2

  • 1Department of Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.

Neurobiology of Learning and Memory
|July 14, 2015
PubMed

Insights

Stress impairs cognitive function by damaging brain cell structures. This study identified key genes and signaling pathways, including Notch and TGF-B, involved in stress-induced dendritic morphology damage.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Stress is known to induce cognitive impairments.
  • These impairments are often linked to damage in brain dendritic morphology.
  • Current treatments for stress-induced cognitive deficits are limited due to unknown underlying molecular mechanisms.

Purpose of the Study:

  • To identify potential molecules and pathways associated with stress-induced damage to dendritic morphology.
  • To investigate the molecular basis of cognitive impairments resulting from stress exposure.

Main Methods:

  • Gene expression analysis in mice brains after 5-hour multimodal stress exposure.
  • Construction of a protein-protein interaction (PPI) network.
  • Molecular pathway analysis using DAVID (Database for Annotation, Visualization, and Integrated Discovery), including Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes).

Main Results:

  • Stress increased corticosterone, decreased cognitive function, and damaged dendritic morphology.
  • Expression of genes including APBB1, CLSTN1, KCNA4, NOTCH3, PLAU, RPS6KA1, SYP, TGFB1, KCNA1, NTRK3, and SNCA were altered.
  • Abnormal expression of CLSTN1, PLAU, NOTCH3, and TGFB1 correlated with dendritic morphology changes and were part of a 55-gene PPI network.
  • Pathway analysis highlighted enrichment in Notch and transforming growth factor-beta (TGF-B) signaling pathways.

Conclusions:

  • TGFB1, PLAU, NOTCH3, and CLSTN1 are suggested to be involved in stress-induced alterations of dendritic morphology.
  • The Notch and TGF-B signaling pathways are implicated in the mechanisms underlying these stress-induced brain changes.
Keywords:
CognitionCorticosteroneDendriteGene expressionHours-long multimodal stress

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