title: Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and behavior.
abstract: Neonates that suffer oxygen deprivation during birth can have long lasting cognitive deficits, such as memory and learning impairments. Hippocampus, one of the main structures that participate in memory and learning processes, is a plastic and dynamic structure that conserves during life span the property of generating new cells which can become neurons, the so-called neurogenesis. The present study investigated whether a model of rat neonatal anoxia, that causes only respiratory distress, is able to alter the hippocampal volume, the neurogenesis rate and has functional implications in adult life. MRI analysis revealed significant hippocampal volume decrease in adult rats who had experienced neonatal anoxia compared to control animals for rostral, caudal and total hippocampus. In addition, these animals also had 55.7% decrease of double-labelled cells to BrdU and NeuN, reflecting a decrease in neurogenesis rate. Finally, behavioral analysis indicated that neonatal anoxia resulted in disruption of spatial working memory, similar to human condition, accompanied by an anxiogenic effect. The observed behavioral alterations caused by oxygen deprivation at birth might represent an outcome of the decreased hippocampal neurogenesis and volume, evidenced by immunohistochemistry and MRI analysis. Therefore, based on current findings we propose this model as suitable to explore new therapeutic approaches.
authors.affiliation: Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil; Núcleo de Cognição e Sistemas Complexos, Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, Santo André, Brazil. Electronic address: silviahonda@usp.br.
authors.forename: Silvia Honda
authors.initials: SH
authors.lastname: Takada
authors.affiliation: Departamento de Fisiologia Geral, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Lívia Clemente
authors.initials: LC
authors.lastname: Motta-Teixeira
authors.affiliation: Departamento de Fisiologia Geral, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Aline Vilar
authors.initials: AV
authors.lastname: Machado-Nils
authors.affiliation: Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Vitor Yonamine
authors.initials: VY
authors.lastname: Lee
authors.affiliation: Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Sampaio
authors.affiliation: Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Roberson Saraiva
authors.initials: RS
authors.lastname: Polli
authors.affiliation: Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Jackeline Moraes
authors.initials: JM
authors.lastname: Malheiros
authors.affiliation: Departamento de Morfologia e Patologia, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, Brazil.
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: Takase
authors.affiliation: Núcleo de Cognição e Sistemas Complexos, Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, Santo André, Brazil.
authors.forename: Alexandre Hiroaki
authors.initials: AH
authors.lastname: Kihara
authors.affiliation: Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Luciene
authors.initials: L
authors.lastname: Covolan
authors.affiliation: Departamento de Fisiologia Geral, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Gilberto Fernando
authors.initials: GF
authors.lastname: Xavier
authors.affiliation: Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Maria Inês
authors.initials: MI
authors.lastname: Nogueira
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000209:etiology* / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology*; D000860:Hypoxia / Q000150:complications*; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000209:etiology* / Q000503:physiopathology; D008570:Memory, Short-Term / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D065852:Spatial Memory / Q000502:physiology*
keywords: Anxiety; Hippocampal neurogenesis; MRI; Neonatal anoxia; Working memory