Loss of GABAergic inputs in APP/PS1 mouse model of Alzheimer's disease
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1
Janssen Pharmaceuticals, Belgium
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2
Université catholique de Louvain, Belgium
Alzheimer's disease (AD) is characterized by symptoms which include seizures, sleep disruption, loss of memory as well as anxiety in patients. Of particular importance is the possibility of preventing the progressive loss of neuronal projections in the disease.
Transgenic mice overexpressing EOFAD mutant PS1 (L166P) and mutant APP (APP KM670/671NL Swedish) (APP/PS1) develop a very early and robust Amyloid pathology and display synaptic plasticity impairments and cognitive dysfunction. Here we investigated GABAergic neurotransmission, using multi-electrode array (MEA) technology and pharmacological manipulation to quantify the effect of GABA Blockers on field excitatory postsynaptic potentials (fEPSP), and immunostaining of GABAergic neurons.
Using MEA technology we confirm impaired LTP induction by high frequency stimulation in APPPS1 hippocampal CA1 region that was associated with reduced alteration of the pair pulse ratio after LTP induction. Synaptic dysfunction was also observed under manipulation of external Calcium concentration and input-output curve. Electrophysiological recordings from brain slice of CA1 hippocampus area, in the presence of GABAergic receptors blockers cocktails further demonstrated significant reduction in the GABAergic inputs in APP/PS1 mice. Moreover, immunostaining of GAD65 a specific marker for GABAergic neurons revealed reduction of the GABAergic inputs in CA1 area of the hippocampus. These results might be linked to increased seizure sensitivity, premature death and cognitive dysfunction in this animal model of AD. Further in depth analysis of GABAergic dysfunction in APP/PS1 mice is required and may open new perspectives for AD therapy by restoring GABAergic function.
Keywords:
GABAergic transmission,
Plasticity and Learning,
Alzheimer Disease,
multielectrode recordings,
hyperexcitability
Conference:
4th NAMASEN Training Workshop - Dendrites 2014, Heraklion, Greece, 1 Jul - 4 Jul, 2014.
Presentation Type:
Poster presentation
Topic:
functional or structural plasticity and homeostasis
Citation:
Oyelami
T,
Dewachter
I and
Shaban
H
(2014). Loss of GABAergic inputs in APP/PS1 mouse model of Alzheimer's disease.
Front. Syst. Neurosci.
Conference Abstract:
4th NAMASEN Training Workshop - Dendrites 2014.
doi: 10.3389/conf.fnsys.2014.05.00041
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Received:
11 Apr 2014;
Published Online:
12 Jun 2014.
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Correspondence:
Ms. Tutu Oyelami, Janssen Pharmaceuticals, Beerse, Belgium, tutu.oyelami@gmail.com