RESUMO
Here we describe a novel mouse model of temporal lobe epilepsy (TLE) that moves the site of kainate injection from the rodent dorsal hippocampus (corresponding to the human posterior hippocampus) to the ventral hippocampus (corresponding to the human anterior hippocampus). We compare the phenotypes of this new model-with respect to seizures, cognitive impairment, affective deficits, and histopathology-to the standard dorsal intrahippocampal kainate model. Our results demonstrate that histopathological measures of granule cell dispersion and mossy fiber sprouting maximize near the site of kainate injection. Somewhat surprisingly, both the dorsal and ventral models exhibit similar spatial memory impairments in addition to similar electrographic and behavioral seizure burdens. In contrast, we find a more pronounced affective (anhedonic) phenotype specifically in the ventral model. These results demonstrate that the ventral intrahippocampal kainic acid model recapitulates critical pathologies of the dorsal model while providing a means to further study affective phenotypes such as depression in TLE.
Assuntos
Anedonia , Ansiedade , Comportamento Animal , Disfunção Cognitiva , Modelos Animais de Doenças , Epilepsia do Lobo Temporal , Agonistas de Aminoácidos Excitatórios/farmacologia , Hipocampo/efeitos dos fármacos , Ácido Caínico/farmacologia , Anedonia/efeitos dos fármacos , Anedonia/fisiologia , Animais , Ansiedade/induzido quimicamente , Ansiedade/etiologia , Ansiedade/fisiopatologia , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Giro Denteado/efeitos dos fármacos , Eletroencefalografia , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/fisiopatologia , Agonistas de Aminoácidos Excitatórios/administração & dosagem , Feminino , Humanos , Ácido Caínico/administração & dosagem , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Fibras Musgosas Hipocampais/efeitos dos fármacosRESUMO
Early detection of Alzheimer's disease (AD) raises a number of challenging legal questions. In this essay, we explore some of those questions, such as: Is a neurological indicator of increased risk for AD a legally relevant brain state before there are any outward behavioral manifestations? How should courts address evidentiary challenges to the admissibility of AD-related neuroimaging? How should the government regulate the marketing of neuroimaging diagnostic tools? How should insurance coverage for the use of these new tools be optimized? We suggest that many voices and multidisciplinary perspectives are needed to answer these questions and ensure that legal responses are swift, efficient, and equitable.
