EVALUATION OF MEMANTINE EFFECTS ON THE BEHAVIORAL PHENOTYPE OF A TDP-43 TRANSGENIC MODEL OF FRONTOTEMPORAL DEMENTIA.

ALFIERI JA; DOMBROVSKY NS; IGAZ LM

Congreso; XXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia (SAN); 2012

Sociedad Argentina de Investigación en Neurociencia (SAN)

TDP-43 is a major disease protein found in most patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), among other neurodegenerative diseases. The NMDA receptor antagonist memantine has been clinically used for the treatment of Alzheimer?s disease and other dementias. The purpose of this study was to evaluate if memantine treatment reversed or slowed the behavioral impairments displayed by an transgenic mice with conditional overexpression of a cytoplasmically-localized form of human TDP-43. This disease model recapitulates key aspects of FTLD and develops behavioral abnormalities, including altered rotarod performance, spontaneous hyperlocomotion in the open field test and a higher level of disinhibition in the elevated plus maze test. We report here that chronic treatment (1 month) with 30 mg/kg/day memantine, a dose with benefitial effects on several murine models of neurodegenerative diseases, did not alter the expression pattern or distribution of TDP-43. Moreover, memantine treatment did not produce significant changes in the behavioral phenotypes described above. Further studies using different doses and treatment times would be required to elucidate if memantine produces significant behavioral and neuroprotective effects in this animal model.