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Effects of synaptic modulation on β-amyloid, synaptophysin, and memory performance in Alzheimer's disease transgenic mice

Tampellini, Davide LU ; Capetillo-Zarate, Estibaliz ; Dumont, Magali ; Huang, Zhenyong ; Yu, Fangmin ; Lin, Michael T. and Gouras, Gunnar K. LU (2010) In Journal of Neuroscience 30(43). p.14299-14304
Abstract

Accumulation of β-amyloid (Aβ) and loss of synapses are hallmarks of Alzheimer's disease (AD). How synaptic activity relates to Aβ accumulation and loss of synapses is a current topic of major interest. Synaptic activation promotes Aβ secretion, and chronic reduction of synaptic activity reduced Aβ plaques in an AD transgenic mouse model. This suggested beneficial effects of reducing synaptic activity in AD. We now show that reduced synaptic activity causes detrimental effects on synapses and memory despite reducing plaques using two different models of chronic synaptic inhibition: deafferentation of the barrel cortex and administration of benzodiazepine. An interval of prolonged synaptic inhibition exacerbated loss of synaptophysin... (More)

Accumulation of β-amyloid (Aβ) and loss of synapses are hallmarks of Alzheimer's disease (AD). How synaptic activity relates to Aβ accumulation and loss of synapses is a current topic of major interest. Synaptic activation promotes Aβ secretion, and chronic reduction of synaptic activity reduced Aβ plaques in an AD transgenic mouse model. This suggested beneficial effects of reducing synaptic activity in AD. We now show that reduced synaptic activity causes detrimental effects on synapses and memory despite reducing plaques using two different models of chronic synaptic inhibition: deafferentation of the barrel cortex and administration of benzodiazepine. An interval of prolonged synaptic inhibition exacerbated loss of synaptophysin compared with synaptically more active brain in AD transgenic but not wild-type mice. Furthermore, an interval of benzodiazepine treatment, followed by a washout period, exacerbated memory impairment in AD transgenic mice. Exacerbation of synaptic and behavioral abnormalities occurred in the setting of reduced Aβ plaques but elevated intraneuronal Aβ immunoreactivity. These data support beneficial effects of synaptic activation on Aβ-related synaptic and behavioral impairment in AD.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Neuroscience
volume
30
issue
43
pages
14299 - 14304
publisher
Society for Neuroscience
external identifiers
  • pmid:20980585
  • scopus:78049349176
ISSN
0270-6474
DOI
10.1523/JNEUROSCI.3383-10.2010
language
English
LU publication?
no
id
1e77c251-71a3-4ac0-b8b8-9acaad34dbd4
date added to LUP
2020-02-20 14:16:29
date last changed
2020-09-30 06:34:54
@article{1e77c251-71a3-4ac0-b8b8-9acaad34dbd4,
  abstract     = {<p>Accumulation of β-amyloid (Aβ) and loss of synapses are hallmarks of Alzheimer's disease (AD). How synaptic activity relates to Aβ accumulation and loss of synapses is a current topic of major interest. Synaptic activation promotes Aβ secretion, and chronic reduction of synaptic activity reduced Aβ plaques in an AD transgenic mouse model. This suggested beneficial effects of reducing synaptic activity in AD. We now show that reduced synaptic activity causes detrimental effects on synapses and memory despite reducing plaques using two different models of chronic synaptic inhibition: deafferentation of the barrel cortex and administration of benzodiazepine. An interval of prolonged synaptic inhibition exacerbated loss of synaptophysin compared with synaptically more active brain in AD transgenic but not wild-type mice. Furthermore, an interval of benzodiazepine treatment, followed by a washout period, exacerbated memory impairment in AD transgenic mice. Exacerbation of synaptic and behavioral abnormalities occurred in the setting of reduced Aβ plaques but elevated intraneuronal Aβ immunoreactivity. These data support beneficial effects of synaptic activation on Aβ-related synaptic and behavioral impairment in AD.</p>},
  author       = {Tampellini, Davide and Capetillo-Zarate, Estibaliz and Dumont, Magali and Huang, Zhenyong and Yu, Fangmin and Lin, Michael T. and Gouras, Gunnar K.},
  issn         = {0270-6474},
  language     = {eng},
  month        = {10},
  number       = {43},
  pages        = {14299--14304},
  publisher    = {Society for Neuroscience},
  series       = {Journal of Neuroscience},
  title        = {Effects of synaptic modulation on β-amyloid, synaptophysin, and memory performance in Alzheimer's disease transgenic mice},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.3383-10.2010},
  doi          = {10.1523/JNEUROSCI.3383-10.2010},
  volume       = {30},
  year         = {2010},
}