Expression of layer-specific markers in the adult neocortex of BCNU-Treated rat, a model of cortical dysplasia

Moroni, Ramona Frida; Inverardi, Francesca; Regondi, Maria Cristina; Watakabe, Akiya; Yamamori, Tetsuo; Spreafico, Roberto; Frassoni, Carolina

doi:10.1016/j.neuroscience.2008.12.064

Cited by 26 publications

(32 citation statements)

References 31 publications

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“…At E21, most of the electroporated cells arrested in the VZ began to express Satb2 (marker of upper layer neurons) [31], while they were negative for Tbr1 (marker of layer VI) [32], thus proving that these cells became postmitotic neurons destined to supragranular layers. Both at E21 and at P7, periventricular heterotopia consisted mainly of Satb2+ cells, whereas Tbr1+ neurons were located at their border, thus showing a pseudolaminar structure and confirming our previous findings that demonstrated a rudimentary laminar organization of the nodular formations [10,11]. Another feature of BCNU-treated cortex was the presence of cortical heterotopia, i.e.…”

Section: Discussionsupporting

confidence: 88%

“…The main finding of this study concerns the ontogenesis of periventricular heterotopia, an additional feature revealed in the BCNU-treated rats during adulthood and development [9,10,11]. Contrary to what has been previously described, in which periventricular heterotopia were detected since P1 [11], here we identified periventricular heterotopia already during embryonic development and we traced back their origin at E18.…”

Section: Discussionmentioning

confidence: 39%

“…The BCNU-treated rats represent an injury-based model of cortical malformations mimicking the histopathological abnormalities observed in human CD patients [9,10]. The expression analysis of some layer-specific markers during embryonic and postnatal development has strongly suggested defects in neuronal migration and a rudimentary laminar pattern of the periventricular nodule found in BCNU-exposed cortex [11].…”

Section: Discussionmentioning

confidence: 99%

“…Another feature of BCNU-treated cortex was the presence of cortical heterotopia, i.e. heterotopic neuronal clusters largely localized in infragranular layers at the intermediate rostrocaudal level of the somatosensory cortex [9,10]. Unfortunately, we were unable to find these neuronal clusters by means of GFP in utero electroporation, probably because of the constricted area that is transfected in both the medial-lateral and rostrocaudal extensions of the brain, which probably has not covered the above-mentioned alterations.…”

Section: Discussionmentioning

confidence: 99%

“…The cytological and histological alterations of this model have been widely investigated in both adult and developing animals by means of immunohistochemical markers recognizing interneurons or pyramidal neurons, by analyzing the expression pattern of an appropriate panel of cortical layer-specific genes and by using magnetic resonance imaging [9,10,11]. Changes in neocortical organization of BCNU-treated rats have been revealed since the embryonic stages, when the disorganization of the ventricular wall, the disruption of the radial and tangential fibers, and the defective organization of the CP and subplate can be observed [9,10,11]. …”

Section: Introductionmentioning

confidence: 99%

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Genesis of Heterotopia in BCNU Model of Cortical Dysplasia, Detected by Means of in utero Electroporation

Moroni¹,

Inverardi²,

Regondi³

et al. 2013

Dev Neurosci

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Derangements of cortical development can cause a wide spectrum of malformations, generally termed ‘cortical dysplasia' (CD), which are frequently associated with drug-resistant epilepsy and other neurological and mental disorders. 1,3-Bis-chloroethyl-nitrosurea (BCNU)-treated rats represent a model of CD due to the presence of histological alterations similar to those observed in human CD. BCNU is an alkylating agent that, administered at embryonic day 15 (E15), causes the loss of many cells destined to cortical layers; this results in cortical thinning but also in histological alterations imputable to migration defects, such as laminar disorganization and cortical and periventricular heterotopia. In the present study we investigated the genesis of heterotopia in BCNU-treated rats by labeling cortical ventricular zone (VZ) cells with a green fluorescent protein (GFP) expression vector by means of in utero electroporation. Here, we compared the migratory pattern and subsequent distribution of the GFP-labeled cells in the developing somatosensory cortex of control and BCNU-treated animals. To this aim, we investigated the expression of a panel of developmental marker genes which identified radial glia cells (Pax6), intermediate precursors cells (Tbr2), and postmitotic neurons destined to infragranular (Tbr1) or supragranular layers (Satb2). The VZ of BCNU-treated rats appeared disorganized since E18 and at E21 the embryos showed an altered migratory pattern: migration of superficial layers appeared delayed, with a number of migrating cells in the intermediate zone and some neurons destined to superficial layers arrested in the VZ, thus forming periventricular heterotopia. Moreover, neurons that reached their correct position did not extend their axons through the corpus callosum in the contralateral hemisphere as in the control, but toward the ipsilateral cingulated cortex. Our analysis sheds light on how a malformed cortex develops after a temporally discrete environmental insult.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 39%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Genesis of Heterotopia in BCNU Model of Cortical Dysplasia, Detected by Means of in utero Electroporation

Moroni¹,

Inverardi²,

Regondi³

et al. 2013

Dev Neurosci

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Mapping the distribution of language related genes FoxP1, FoxP2, and CntnaP2 in the brains of vocal learning bat species

Rodenas-Cuadrado

Mengede

Baas

et al. 2018

J of Comparative Neurology

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Genes including FOXP2, FOXP1, and CNTNAP2, have been implicated in human speech and language phenotypes, pointing to a role in the development of normal language‐related circuitry in the brain. Although speech and language are unique to humans a comparative approach is possible by addressing language‐relevant traits in animal systems. One such trait, vocal learning, represents an essential component of human spoken language, and is shared by cetaceans, pinnipeds, elephants, some birds and bats. Given their vocal learning abilities, gregarious nature, and reliance on vocalizations for social communication and navigation, bats represent an intriguing mammalian system in which to explore language‐relevant genes. We used immunohistochemistry to detail the distribution of FoxP2, FoxP1, and Cntnap2 proteins, accompanied by detailed cytoarchitectural histology in the brains of two vocal learning bat species; Phyllostomus discolor and Rousettus aegyptiacus. We show widespread expression of these genes, similar to what has been previously observed in other species, including humans. A striking difference was observed in the adult P. discolor bat, which showed low levels of FoxP2 expression in the cortex that contrasted with patterns found in rodents and nonhuman primates. We created an online, open‐access database within which all data can be browsed, searched, and high resolution images viewed to single cell resolution. The data presented herein reveal regions of interest in the bat brain and provide new opportunities to address the role of these language‐related genes in complex vocal‐motor and vocal learning behaviors in a mammalian model system.

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The application of cortical layer markers in the evaluation of cortical dysplasias in epilepsy

et al. 2010

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The diagnostic criteria for focal cortical dysplasia type I (FCD I) remain to be well and consistently defined. Cortical layer-specific markers (CLM) provide a potential tool for the objective assessment of any dyslamination. We studied expression patterns of recognised CLM using immunohistochemistry for N200, ER81, Otx1, Map1b (subsets of V/VI projection neurones), Pax6, Tbr1, Tbr2 (differentially expressed in cortical neurones from intermediate progenitor cells), Cux 1 (outer cortical layers) and MASH1 (ventricular zone progenitors). Dysplasia subtypes included FCD I and II, dysplasias adjacent to hippocampal sclerosis (HS) or dysembryoplastic neuroepithelial tumours (DNTs); all were compared to neonatal and adult controls. Laminar expression patterns in normal cortex were observed with Tbr1, Map1b, N200 and Otx1. FCDI cases in younger patients were characterised by abnormal expression in layer II for Tbr1 and Otx1. FCDII showed distinct labelling of balloon cells (Pax6, ER81 and Otx1) and dysmorphic neurones (Tbr 1, N200 and Map1b) supporting origins from radial glia and intermediate progenitor cells, respectively. In temporal lobe sclerosis cases with dysplasia adjacent to HS, Tbr1 and Map1b highlighted abnormal orientation of neurones in layer II. Dyslamination was not confirmed in the perilesional cortex of DNT with CLM. Finally, immature cell types (Otx1, Pax6 and Tbr2) were noted in varied pathologies. One possibility is activation of progenitor cell populations which could contribute to the pathophysiology of these lesions.

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Expression of layer-specific markers in the adult neocortex of BCNU-Treated rat, a model of cortical dysplasia

Cited by 26 publications

References 31 publications

Genesis of Heterotopia in BCNU Model of Cortical Dysplasia, Detected by Means of in utero Electroporation

Genesis of Heterotopia in BCNU Model of Cortical Dysplasia, Detected by Means of in utero Electroporation

Mapping the distribution of language related genes FoxP1, FoxP2, and CntnaP2 in the brains of vocal learning bat species

The application of cortical layer markers in the evaluation of cortical dysplasias in epilepsy

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