Molecular changes in brain aging and Alzheimer's disease are mirrored in experimentally silenced cortical neuron networks

Marc Gleichmann, Yongqing Zhang, William H. Wood, Kevin G. Becker, Mohamed R. Mughal, Michael J. Pazin, Henriette van Praag, Tali Kobilo, Alan B. Zonderman, Juan C Troncoso, William R. Markesbery, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

Activity-dependent modulation of neuronal gene expression promotes neuronal survival and plasticity, and neuronal network activity is perturbed in aging and Alzheimer's disease (AD). Here we show that cerebral cortical neurons respond to chronic suppression of excitability by downregulating the expression of genes and their encoded proteins involved in inhibitory transmission (GABAergic and somatostatin) and Ca 2+ signaling; alterations in pathways involved in lipid metabolism and energy management are also features of silenced neuronal networks. A molecular fingerprint strikingly similar to that of diminished network activity occurs in the human brain during aging and in AD, and opposite changes occur in response to activation of N-methyl-D-aspartate (NMDA) and brain-derived neurotrophic factor (BDNF) receptors in cultured cortical neurons and in mice in response to an enriched environment or electroconvulsive shock. Our findings suggest that reduced inhibitory neurotransmission during aging and in AD may be the result of compensatory responses that, paradoxically, render the neurons vulnerable to Ca 2+-mediated degeneration.

Original languageEnglish (US)
JournalNeurobiology of Aging
Volume33
Issue number1
DOIs
StatePublished - Jan 2012

Fingerprint

Brain Diseases
Alzheimer Disease
Neurons
trkB Receptor
Gene Expression
Electroshock
Neuronal Plasticity
Dermatoglyphics
N-Methylaspartate
Somatostatin
Lipid Metabolism
Synaptic Transmission
Down-Regulation
Brain
Proteins

Keywords

  • Activity
  • Aging
  • Alzheimer's disease
  • Calcium
  • GABA
  • Homeostatic disinhibition
  • Interneuron
  • Synaptic scaling

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Molecular changes in brain aging and Alzheimer's disease are mirrored in experimentally silenced cortical neuron networks. / Gleichmann, Marc; Zhang, Yongqing; Wood, William H.; Becker, Kevin G.; Mughal, Mohamed R.; Pazin, Michael J.; van Praag, Henriette; Kobilo, Tali; Zonderman, Alan B.; Troncoso, Juan C; Markesbery, William R.; Mattson, Mark P.

In: Neurobiology of Aging, Vol. 33, No. 1, 01.2012.

Research output: Contribution to journalArticle

Gleichmann, M, Zhang, Y, Wood, WH, Becker, KG, Mughal, MR, Pazin, MJ, van Praag, H, Kobilo, T, Zonderman, AB, Troncoso, JC, Markesbery, WR & Mattson, MP 2012, 'Molecular changes in brain aging and Alzheimer's disease are mirrored in experimentally silenced cortical neuron networks', Neurobiology of Aging, vol. 33, no. 1. https://doi.org/10.1016/j.neurobiolaging.2010.08.012
Gleichmann, Marc ; Zhang, Yongqing ; Wood, William H. ; Becker, Kevin G. ; Mughal, Mohamed R. ; Pazin, Michael J. ; van Praag, Henriette ; Kobilo, Tali ; Zonderman, Alan B. ; Troncoso, Juan C ; Markesbery, William R. ; Mattson, Mark P. / Molecular changes in brain aging and Alzheimer's disease are mirrored in experimentally silenced cortical neuron networks. In: Neurobiology of Aging. 2012 ; Vol. 33, No. 1.
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