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Related Experiment Video

Updated: Aug 6, 2025

Analysis of Dendritic Spine Morphology in Cultured CNS Neurons
11:48

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Reelin and APP Cooperatively Modulate Dendritic Spine Formation In Vitro and In Vivo.

Hyun-Ju Lee1, Jin-Hee Park1,2, Justin H Trotter3

  • 1Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), Daegu 41062, Korea.

Experimental Neurobiology
|March 15, 2023
PubMed
Summary

Reelin enhances dendritic spine formation, crucial for learning and memory, by working with Amyloid precursor protein (APP). Normal APP function is essential for Reelin

Keywords:
APPAlzheimer’s diseaseDendritic spineRas signalingReelin

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Area of Science:

  • Neuroscience
  • Cell Biology

Background:

  • Amyloid precursor protein (APP) is implicated in Alzheimer's disease pathogenesis.
  • The precise role of APP in synaptic function, particularly dendritic spine formation, remains unclear.
  • APP interacts with Reelin, a protein vital for dendritic spine development.

Purpose of the Study:

  • To investigate whether Reelin modulates dendritic spine formation and synaptic function through APP.
  • To elucidate the molecular mechanisms underlying Reelin-mediated dendritic spinogenesis.

Main Methods:

  • Primary hippocampal neurons were treated with Reelin.
  • Dendritic spine density and PSD-95 puncta were quantified.
  • APP expression was manipulated (reduction and knockout) to assess its role.
  • Ras/ERK/CREB signaling pathways were examined.

Main Results:

  • Reelin treatment significantly increased dendritic spine density and PSD-95 puncta in hippocampal neurons.
  • Reelin-induced dendritic spine formation was dependent on Ras/ERK/CREB signaling.
  • Reelin failed to increase dendritic spine number in neurons with reduced APP or in APP knockout mice.

Conclusions:

  • Reelin acts cooperatively with APP to regulate dendritic spine formation.
  • Normal APP function is critical for Reelin-mediated dendritic spinogenesis at synapses.
  • These findings highlight a novel interaction between Reelin and APP in synaptic plasticity.