Behavior, electrographic, neutopathological and molecular alterations induced in two animals models of temporal lobe epilepsy: possible relationship between cognitive deficits and psychotic symptoms

Abstract

The mesial temporal lobe epilepsy (MTLE) is the most common form of focal epilepsy in adults. The MTLE is often associated with hippocampal sclerosis (HS), which is characterized by selective neuronal loss and aberrant axonal sprouting of mossy fibers in the dentate gyrus. Although EH is well described in MTLE, less is known about the involvement of other limbic regions related to the hippocampus, such as the midline thalamus and prefrontal cortex, where electrographic seizures can spread when they become secondarily generalized. In fact, these limbic circuits are affected in conditions of cognitive impairment and psychosis, which are comorbidities with a high prevalence in patients with MTLE. Considering that the co-occurrence of psychotic symptoms and cognitive impairments is still poorly studied in animal models of MTLE, our objective is to compare two models of MTLE in rats (intra-hippocampal injection of the muscarinic agonist pilocarpine, or low-intensity continuous and focal electrical stimulation in the perforant pathway) for study of spatial working memory performance, symptoms of psychosis and neuropathological/molecular abnormalities. For that, we will evaluate: (1) behavioral and electrographic expressions of limbic seizures, (2) performance on training in an eight-arm radial maze, (3) exploratory behavior in an open field arena, as well as effectiveness of inhibition of the acoustic startle for testing of psychosis, and (4) neuropathological (neuronal density and axonal sprouting) and molecular (expression of GAD65/67, BDNF and trkB) alterations. Thus, we intend to contribute to a better understanding of shared neuropathological bases between MTLE, related cognitive deficits, and the spectrum of clinically frequent psychiatric comorbidities. (AU)