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CORONAVIRUS COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU) ...

lunes, 25 de diciembre de 2017

La rapamicina mejora la plasticidad cerebral y la memoria en ratones con síndrome de Down

Rapamycin restores BDNF-LTP and the persistence of long-term memory in a model of Down's síndrome


Abstract

Down's syndrome (DS) is the most prevalent genetic intellectual disability. Memory deficits significantly contribute to the cognitive dysfunction in DS. Previously, we discovered that mTOR-dependent local translation, a pivotal process for some forms of synaptic plasticity, is deregulated in a DS mouse model. Here, we report that these mice exhibit deficits in both synaptic plasticity (i.e., BDNF-long term potentiation) and the persistence of spatial long-term memory. Interestingly, these deficits were fully reversible using rapamycin, a Food and Drug Administration-approved specific mTOR inhibitor; therefore, rapamycin may be a novel pharmacotherapy to improve cognition in DS.
Abbreviations
4EBPs
eIF4E-binding proteins
AMPA
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
BDNF
brain-derived neurotrophic factor
CHX
cycloheximide
DG
dentate gyrus
DS
Down's syndrome
eIF4E
eukaryotic translation initiation factor 4E
ERK
extracellular signal-regulated kinase
FDA
Food and Drug Administration
fEPSPs
field excitatory postsynaptic potentials
GABA
gamma-aminobutyric acid
HFS
high frequency stimulation
LTD
long-term depression
LTM
long-term memory
LTP
Long-term potentiation
MEK
MAPK/ERK kinase
Mnk1
mitogen-activated protein kinase integrating kinase 1
mTOR
mammalian target of rapamycin
NMDAR
N-methyl D-aspartate receptor
p70S6K
p70 S6 kinase
PDK1
phosphoinositide-dependent kinase 1
PI3K
phosphatidylinositol 3-kinase
PIP2
phosphatidilynositol 4,5-bisphosphate
PIP3
phosphatidylinositol 3,4,5-trisphosphate
PPF
paired-pulse facilitation
PPR
paired-pulse ratio
PTEN
Phosphatase and tensin homolog on chromosome ten
RSK
p90 ribosomal S6 kinase
TrkB
tropomyosin-related kinase B
TSC
tuberous sclerosis complex
WT
wild-type

Keywords


Barnes maze
BDNF-LTP
ERK
MTOR
Pharmacotherapy
Rapamycin
Synaptic plasticity
Trisomy 21
Ts1Cje

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