Grant: Operating Grant

Epilepsy is a chronic neurological disorder characterized by the occurrence of spontaneous recurrent seizures. It affects about 50 million people worldwide and its prevalence increases with age especially in population with dementia. Temporal lobe epilepsy (TLE) is the most common form of human epilepsy with recurrent seizures originating from mesial structure such as hippocampus and then propagates to other brain structures. One of the major pathological features associated with TLE is the "hippocampal sclerosis" which is characterized by atrophy, glial proliferation and loss of neurons in selected regions of the hippocampus. There is evidence that increased level of the excitatory neurotransmitter glutamate plays a critical role in the generation of seizures as well as loss of neurons in TLE patients, but the underlying cellular mechanisms remain unclear. Evidence assimilated over the last decade indicate that increased levels of glutamate is involved not only in TLE but also in the degeneration of neurons trigger by amyloid beta (Ab) peptides, which are critical in the development of Alzheimer's disease pathology, the most common type of dementia affecting the elderly population. These results, together with the evidence of Ab deposition in the brain of some TLE patients, raise the possibility that Ab peptides may have a role in the loss of neurons in TLE. To address this issue our laboratory is currently investigating the implications of Ab peptides in the development of seizures and loss of neurons observed in animal model of TLE as well as in mice that have been genetically modified to produce excess Ab peptides. Additionally, we will measure the levels of Ab peptide in the brain samples obtained from patients with TLE. This study will determine the underlying basis of a role for Ab peptides in TLE and will define whether inhibition of Ab production can attenuate the degeneration of neurons and/or progression disease pathology in epilepsy.