title: Cytoarchitectural, behavioural and neurophysiological dysfunctions in the BCNU-treated rat model of cortical dysplasia.
abstract: Cortical dysplasias (CDs) include a spectrum of cerebral lesions resulting from cortical development abnormalities during embryogenesis that lead to cognitive disabilities and epilepsy. The experimental model of CD obtained by means of in utero administration of BCNU (1-3-bis-chloroethyl-nitrosurea) to pregnant rats on embryonic day 15 mimics the histopathological abnormalities observed in many patients. The aim of this study was to investigate the behavioural, electrophysiological and anatomical profile of BCNU-treated rats in order to determine whether cortical and hippocampal lesions can directly lead to cognitive dysfunction. The BCNU-treated rats showed impaired short-term working memory but intact long-term aversive memory, whereas their spontaneous motor activity and anxiety-like response were normal. The histopathological and immunohistochemical analyses, made after behavioural tests, revealed the disrupted integrity of neuronal populations and connecting fibres in hippocampus and prefrontal and entorhinal cortices, which are involved in memory processes. An electrophysiological evaluation of the CA1 region of in vitro hippocampal slices indicated a decrease in the efficiency of excitatory synaptic transmission and impaired paired pulse facilitation, but enhanced long-term potentiation (LTP) associated with hyperexcitability in BCNU-treated rats compared with controls. The enhanced LTP, associated with hyperexcitability, may indicate a pathological distortion of long-term plasticity. These findings suggest that prenatal developmental insults at the time of peak cortical neurogenesis can induce anatomical abnormalities associated with severe impairment of spatial working memory in adult BCNU-treated rats and may help to clarify the pathophysiological mechanisms of cognitive dysfunction that is often associated with epilepsy in patients with CD.
authors.affiliation: Clinical Epileptology and Experimental Neurophysiology Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Inverardi
authors.forename: Maia
authors.initials: M
authors.lastname: Chikhladze
authors.forename: Andrea
authors.initials: A
authors.lastname: Donzelli
authors.forename: Ramona Frida
authors.initials: RF
authors.lastname: Moroni
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Regondi
authors.forename: Paolo
authors.initials: P
authors.lastname: Pennacchio
authors.forename: Ileana
authors.initials: I
authors.lastname: Zucca
authors.forename: Irene
authors.initials: I
authors.lastname: Corradini
authors.forename: Daniela
authors.initials: D
authors.lastname: Braida
authors.forename: Mariaelvina
authors.initials: M
authors.lastname: Sala
authors.forename: Silvana
authors.initials: S
authors.lastname: Franceschetti
authors.forename: Carolina
authors.initials: C
authors.lastname: Frassoni
mesh_terms: D000818:Animals; D002330:Carmustine; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000187:drug effects / Q000196:embryology / Q000473:pathology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000196:embryology / Q000473:pathology*; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology / Q000473:pathology*; D017774:Long-Term Potentiation / Q000187:drug effects; D054220:Malformations of Cortical Development / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D057567:Memory, Long-Term / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009412:Nerve Fibers / Q000473:pathology; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D002330:Carmustine