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ADAM-10 over-expression increases cortical synaptogenesis.

Karen F S Bell1, Luyu Zheng, Falk Fahrenholz

  • 1Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.

Neurobiology of Aging
|December 26, 2006
PubMed
Summary
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Increased ADAM-10 expression boosts brain synapses, particularly cholinergic ones, in early stages. This study confirms the neurotrophic role of sAPP alpha in synaptic plasticity and synaptogenesis.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Synaptic Plasticity

Background:

  • Cortical neurotransmitter systems are altered in early amyloid pathology.
  • Soluble amyloid precursor protein alpha (sAPP alpha) exhibits neurotrophic properties.
  • ADAM-10 possesses alpha-secretase activity, suggesting a role in sAPP alpha production.

Purpose of the Study:

  • To investigate the in vivo influence of ADAM-10 on cortical presynaptic bouton densities.
  • To determine the endogenous biological effect of sAPP alpha on cortical synaptogenesis.
  • To examine the impact of ADAM-10 overexpression on cholinergic, glutamatergic, and GABAergic terminals.

Main Methods:

  • Quantification of presynaptic bouton densities in ADAM-10 moderate-expressing (ADAM-10 mo) transgenic mice and controls.

Related Experiment Videos

  • Analysis at early (8 months) and late (18 months) developmental time points.
  • Intracortical infusion of exogenous human sAPP alpha into non-transgenic control animals.

    • Main Results:

    • ADAM-10 mo mice showed elevated cholinergic, glutamatergic, and GABAergic bouton densities at 8 months.
    • Only cholinergic bouton density remained significantly elevated in 18-month-old ADAM-10 mo mice.
    • Exogenous sAPP alpha infusion increased all three neurotransmitter-specific presynaptic bouton populations.

    Conclusions:

    • ADAM-10 influences neurotransmitter-specific cortical synaptic plasticity in vivo.
    • Endogenous sAPP alpha, modulated by ADAM-10, promotes cortical synaptogenesis.
    • These findings highlight the neurotrophic role of sAPP alpha in synaptic regulation.