Impact of neonatal anoxia and hypothermic treatment on development and memory of rats

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Vasquez Matsuda, Victor Daniel ^{[1, 2]} ; Bustelo Tejada, Martin ^{[3, 4, 5, 6, 7]} ; Motta-Teixeira, Livia Clemente ^[1] ; Ikebara, Juliane Midori ^[4] ; Cardoso, Debora Sterzeck ^[4] ; Machado-Nils, Aline Vilar ^[1] ; Lee, Vitor Yonamine ^[2] ; Diccini, Isabelle ^[2] ; Arruda, Bruna Petrucelli ^{[2, 4]} ; Martins, Pamela Pinheiro ^[4] ; Morales Dias, Natalia Myuki ^[4] ; Tessarotto, Rafaella Pinto ^[4] ; Raeisossadati, Reza ^[4] ; Bruno, Martin ^{[7, 8]} ; Takase, Luiz Fernando ^[9] ; Kihara, Alexandre Hiroaki ^[4] ; Nogueira, Maria Ines ^[2] ; Xavier, Gilberto Fernando ^[1] ; Takada, Silvia Honda ^[4]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biosci, Dept Physiol, Neurosci & Behav Lab, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Neurosci Lab, Sao Paulo, SP - Brazil

^[3] Maastricht Univ, Sch Mental Hlth & Neurosci MHeNs, Dept Psychiat & Neuropsychol, Maastricht - Netherlands

^[4] Univ Fed ABC, Neurogenet Lab, Alameda Univ, S-N, BR-09606045 Sao Bernardo Do Campo, SP - Brazil

^[5] Maastricht Univ Med Ctr MUMC, Dept Pediat, Maastricht - Netherlands

^[6] Univ Buenos Aires, Fac Med, Inst Cellular Biol & Neurosci Prof & Robertis IBC, Expt Neuropathol Lab, CONICET, Buenos Aires, DF - Argentina

^[7] Catholic Univ Cuyo, Fac Med Sci, Biomed Sci Inst, San Juan - Argentina

^[8] Natl Council Sci & Tech Res CONICET, Buenos Aires, DF - Argentina

^[9] Univ Fed Sao Carlos, Biol Sci & Hlth Ctr, Dept Morphol & Pathol, Sao Carlos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental Neurology; v. 340, JUN 2021.
• Citações Web of Science: 0

Resumo

Therapeutic hypothermia (TH) is well established as a standard treatment for term and near-term infants. However, therapeutic effects of hypothermia following neonatal anoxia in very premature babies remains inconclusive. The present rodent model of preterm neonatal anoxia has been shown to alter developmental milestones and hippocampal neurogenesis, and to disrupt spatial learning and memory in adulthood. These effects seem to be reduced by post-insult hypothermia. Epigenetic-related mechanisms have been postulated as valuable tools for developing new therapies. Dentate gyrus neurogenesis is regulated by epigenetic factors. This study evaluated whether TH effects in a rodent model of preterm oxygen deprivation are based on epigenetic alterations. The effects of TH on both developmental features (somatic growth, maturation of physical characteristics and early neurological reflexes) and performance of behavioral tasks at adulthood (spatial reference and working memory, and fear conditioning) were investigated in association with the possible involvement of the epigenetic operator Enhancer of zeste homolog 2 (Ezh2), possibly related to long-lasting effects on hippocampal neurogenesis. Results showed that TH reduced both anoxia-induced hippocampal neurodegeneration and anoxiainduced impairments on risk assessment behavior, acquisition of spatial memory, and extinction of auditory and contextual fear conditioning. In contrast, TH did not prevent developmental alterations caused by neonatal anoxia and did not restore hippocampal neurogenesis or cause changes in EZH2 levels. In conclusion, despite the beneficial effects of TH in hippocampal neurodegeneration and in reversing disruption of performance of behavioral tasks following oxygen deprivation in prematurity, these effects seem not related to developmental alterations and hippocampal neurogenesis and, apparently, is not caused by Ezh2-mediated epigenetic alteration. (AU)

• Processo FAPESP: 17/26439-0 - Uma abordagem interdisciplinar sobre o papel das junções comunicantes e miRNAs no desenvolvimento e degeneração do sistema nervoso
• Beneficiário: Alexandre Hiroaki Kihara
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/14072-7 - Caracterização da resposta microglial após anóxia neonatal em ratos: da análise celular e molecular ao comportamento e abordagem terapêutica
• Beneficiário: Silvia Honda Takada
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/06731-0 - Análise da distribuição e dos níveis proteicos de EZH2 no hipocampo de ratos após anóxia neonatal
• Beneficiário: Pamela Pinheiro Martins
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 15/18415-8 - Diferenças de gênero no desenvolvimento ontogenético, comportamento e metabolismo energético em ratos submetidos à anóxia neonatal: enfoque no hipocampo, hipotálamo,leptina e células da glia .
• Beneficiário: Maria Inês Nogueira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/18941-4 - Efeitos da ausência da melatonina maternal durante a gestação e lactação sobre o sistema neuroimune da prole.
• Beneficiário: Lívia Clemente Motta Teixeira
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado