Age-dependent concomitant changes in synaptic dysfunction and GABAergic pathway in the APP/PS1 mouse model.
Tutu Oyelami1, An De Bondt2, Ilse Van den Wyngaert3
1Department of Neuroscience, Janssen Research and Development, A Division of Janssen Pharmaceutica NV, Beerse, Belgium; Institute of Neuroscience, Université Catholique de Louvain, Louvain-La-Neuve, Belgium.
Acta Neurobiologiae Experimentalis
|January 18, 2017
Summary
Alzheimer's disease (AD) shows age-dependent synaptic dysfunction and altered GABAergic neurotransmission in aged APPPS1 mice. This imbalance in excitation and inhibition may explain AD symptoms like seizures and sleep disturbances.
Area of Science:
- Neuroscience
- Pathology
- Molecular Biology
Background:
- Synaptic dysfunction is a hallmark of Alzheimer's disease (AD) pathology in animal models.
- Increased neuronal excitability and seizures are observed in AD patients and models, seemingly contradicting reduced synaptic function.
- This suggests a complex interplay between excitatory and inhibitory neuronal mechanisms in AD.
Purpose of the Study:
- To investigate functional deficits in the inhibitory (GABAergic) system in AD.
- To determine if GABAergic system deficits correlate with alterations in the glutamate excitatory pathway.
- To explore the link between age-dependent synaptic dysfunction, excitation/inhibition imbalance, and AD progression.
Main Methods:
- Utilized aged APPPS1 mouse models of Alzheimer's disease.
- Assessed synaptic function and GABAergic neurotransmission.
- Compared findings between younger and aged APPPS1 mouse cohorts.
Main Results:
- Identified age-dependent changes in synaptic function in aged APPPS1 mice.
- Observed alterations in GABAergic neurotransmission accompanying synaptic dysfunction.
- Demonstrated an excitation/inhibition imbalance in aged AD models.
Conclusions:
- Age-dependent alterations in the inhibitory/excitatory balance contribute to Alzheimer's disease progression.
- Impaired GABAergic neurotransmission is a key factor in AD-related synaptic dysfunction.
- This imbalance may underlie AD symptoms such as sleep disturbances and epileptic events.
