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

Author(s):Show less -

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]

Affiliation

^[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

• Document type: Journal article
• Source: Experimental Neurology; v. 340, JUN 2021.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 17/26439-0 - An interdisciplnary approach on the role of gap junctions and miRNAs in the development and degeneration of the nervous system
• Grantee: Alexandre Hiroaki Kihara
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/14072-7 - Characterization of the microglial response after neonatal anoxia in rats: from cellular and molecular analysis to behavioral and therapeutic approach
• Grantee: Silvia Honda Takada
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/06731-0 - Analysis of the distribution and protein levels of EZH2 in the rat hippocampus after neonatal anoxia
• Grantee: Pamela Pinheiro Martins
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 15/18415-8 - Gender differences in ontogenetic development, behavior and energy metabolism in rats subjected to neonatal anoxia: focus on the hippocampus, hypothalamus, leptin and glia cels
• Grantee: Maria Inês Nogueira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/18941-4 - Effects of maternal melatonin deprivation during pregnancy and lactation on the offspring neuroimmune system
• Grantee: Lívia Clemente Motta Teixeira
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate