Basic mechanisms of MCD in animal models.
Epilepsy-associated glioneuronal malformations (malformations of cortical development [MCD]) include focal cortical dysplasias (FCD) and highly differentiated glioneuronal tumors, most frequently gangliogliomas. The neuropathological findings are variable but suggest aberrant proliferation, migration, and differentiation of neural precursor cells as essential pathogenetic elements. Recent advances in animal models for MCDs allow new insights in the molecular pathogenesis of these epilepsy-associated lesions. Novel approaches, presented here, comprise RNA interference strategies to generate and study experimental models of subcortical band heterotopia and study functional aspects of aberrantly shaped and positioned neurons. Exciting analyses address impaired NMDA receptor expression in FCD animal models compared to human FCDs and excitatory imbalances in MCD animal models such as lissencephaly gene ablated mice as well as in utero irradiated rats. An improved understanding of relevant pathomechanisms will advance the development of targeted treatment strategies for epilepsy-associated malformations.
Battaglia
Giorgio
G
Molecular Neuroanatomy and Pathogenesis Unit, IRCCS Foundation Neurological Institute Carlo Besta, Milano, Italy.
Becker
Albert J
AJ
LoTurco
Joseph
J
Represa
Alfonso
A
Baraban
Scott C
SC
Roper
Steven N
SN
Vezzani
Annamaria
A
D000818:Animals; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000254:growth & development* / Q000473:pathology; D004827:Epilepsy / Q000151:congenital / Q000473:pathology*; D006801:Humans; D051379:Mice; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D034622:RNA Interference; D051381:Rats; D013045:Species Specificity