Physical exercise ameliorates gabaergic and glutamateric neurotransmissions in the 3xtgad mouse model

Trabajo presentado al 8th Forum of Neuroscience (FENS) celebrado en Barcelona del 14 al 18 de julio de 2012.Azheimer´s disease (AD) is a progressive neurodegenerative disorder clinically characterized by memory loss and cognitive damage. It presents two main hallmarks: the neurofibrillary tangles formed by the aggregation of p-Tau protein and the senile plaques composed by aggregates of the Aß-42 peptide. It is suggested that in a situation of cholinergic deficit, an imbalance between the excitatory glutamatergic and the inhibitory GABAergic tones may be responsible for cognitive and non-cognitive behavioral disturbances. Participation in a regular exercise program is increasingly proposed as an intervention that could prevent or reduce cognitive and mood disorders of age-associated dementias, mainly in AD. In this work we characterized homozygous 3xTgAD mice on both cognitive and behavioral psychiatric symptoms of dementia (BPSD) and the underlying neuronal changes in order to evaluate the proposed therapeutic effects of physical exercise. Voluntary exercise showed a neuroprotective effect at early stages of AD, including both cognitive and BPSD-like behaviors. Data obtained from neurotransmitter binding experiments showed that exercise improves the functionality of GABAergic receptor, while NMDA receptor was apparently in a more advanced stage of dysfunction because its functional parameters were only partially recovered. Altered expression levels of these receptors subunits, as well as synaptic markers (synaptophysin, PSD95) and neuroprotection-related proteins (Sirt1, GDNF) were normalized by the physical exercise treatment. This work provides more evidence to demonstrate the validity of voluntary exercise as a promising co-adjuvant therapy to prevent or ameliorate AD symptoms and its relevance to be included in our lifestyle.Supported by grant SAF2009-13093-C02-02 from MCINN, Spain.Peer Reviewe