Altered excitatory and inhibitory neocortical circuitry leads to increased convulsive severity after pentylenetetrazol injection in an animal model of schizencephaly, but not of microgyria.

Autor: Dos Santos Heringer L; Neurodegeneration and Repair Lab, Department of Pathology, Postgraduate Program in Anatomical Pathology, Faculty of Medicine, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Rios Carvalho J; Neurodegeneration and Repair Lab, Department of Pathology, Postgraduate Program in Anatomical Pathology, Faculty of Medicine, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Teixeira Oliveira J; D'Or Institute for Research and Teaching, Rio de Janeiro, Brazil., Texeira Silva B; Laboratory of Neuroplasticity, Department of Neurobiology, Institute of Biology, Fluminense Federal University, Niterói, Brazil., de Souza Aguiar Dos Santos DM; Neurodegeneration and Repair Lab, Department of Pathology, Postgraduate Program in Anatomical Pathology, Faculty of Medicine, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Martinez Martinez Toledo AL; Neurodegeneration and Repair Lab, Department of Pathology, Postgraduate Program in Anatomical Pathology, Faculty of Medicine, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Borges Savoldi LM; Neurodegeneration and Repair Lab, Department of Pathology, Postgraduate Program in Anatomical Pathology, Faculty of Medicine, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Magalhães Portela D; Integrated Lab of Morphology, Institute of Biodiversity and Sustainability NUPEM, Multicentric Postgraduate Program in Physiological Sciences - SBFis, Federal University of Rio de Janeiro, Brazil., Adriani Marques S; Neurodegeneration and Repair Lab, Department of Pathology, Postgraduate Program in Anatomical Pathology, Faculty of Medicine, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Campello Costa Lopes P; Laboratory of Neuroplasticity, Department of Neurobiology, Institute of Biology, Fluminense Federal University, Niterói, Brazil., Blanco Martinez AM; Neurodegeneration and Repair Lab, Department of Pathology, Postgraduate Program in Anatomical Pathology, Faculty of Medicine, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Rocha Mendonça H; Neurodegeneration and Repair Lab, Department of Pathology, Postgraduate Program in Anatomical Pathology, Faculty of Medicine, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.; Integrated Lab of Morphology, Institute of Biodiversity and Sustainability NUPEM, Multicentric Postgraduate Program in Physiological Sciences - SBFis, Federal University of Rio de Janeiro, Brazil.
Jazyk: angličtina
Zdroj: Epilepsia open [Epilepsia Open] 2022 Sep; Vol. 7 (3), pp. 462-473. Date of Electronic Publication: 2022 Jul 21.
DOI: 10.1002/epi4.12625
Abstrakt: Objective: Malformations of the polymicrogyria spectrum can be mimicked in rodents through neonatal transcranial focal cortical freeze lesions. The animals presenting the malformations present both altered synaptic events and epileptiform activity in the vicinity of the microgyrus, but the comprehension of their contribution to increased predisposition or severity of seizures require further studies.
Methods: In order to investigate these issues, we induced both microgyria and schizencephaly in 57 mice and evaluated: their convulsive susceptibility and severity after pentyleneterazol (PTZ) treatment, the quantification of their symmetric and asymmetric synapses, the morphology of their dendritic arbors, and the content of modulators of synaptogenesis, such as SPARC, gephyrin and GAP-43 within the adjacent visual cortex.
Results: Our results have shown that only schizencephalic animals present increased convulsive severity. Nevertheless, both microgyric and schizencephalic cortices present increased synapse number and dendritic complexity of layer IV and layer V-located neurons. Specifically, the microgyric cortex presented reduced inhibitory synapses, while the schizencephalic cortex presented increased excitatory synapses. This altered synapse number is correlated with decreased content of both the anti-synaptogenic factor SPARC and the inhibitory postsynaptic organizer gephyrin in both malformed groups. Besides, GAP-43 content and dendritic spines number are enhanced exclusively in schizencephalic cortices.
Significance: In conclusion, our study supports the hypothesis that the sum of synaptic alterations drives to convulsive aggravation in animals with schizencephaly, but not microgyria after PTZ treatment. These findings reveal that different malformations of cortical development should trigger epilepsy via different mechanisms, requiring further studies for development of specific therapeutic interventions.
(© 2022 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Databáze: MEDLINE
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