Behavioral, cognitive and histological changes following neonatal anoxia: Male and female rats' differences at adolescent age

Author(s)

Kumar, Amrita Jha ^[1] ; Motta-Teixeira, Livia Clemente ^{[2, 3]} ; Takada, Silvia Honda ^[4] ; Yonamine-Lee, Vitor ^[1] ; Machado-Nils, Aline Vilar ^[2] ; Xavier, Gilberto Fernando ^[2] ; Nogueira, Maria Ines ^[1]

Affiliation

^[1] Univ Sao Paulo, Neurosci Lab, Dept Anat, Inst Biomed Sci, Av Prof Lineu Prestes 2415, BR-05508900 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Dept Physiol, Inst Biosci, Rua Matao 14, BR-05508900 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Neurobiol Lab, Dept Physiol, Inst Biomed Sci, Av Prof Lineu Prestes 1524, BR-05508900 Sao Paulo, SP - Brazil

^[4] Fed Univ ABC, Neurogenet Lab, Bloco Delta R Arcturus 3, BR-09606070 Sao Bernardo Do Campo, SP - Brazil

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE; v. 73, p. 50-58, APR 2019.
• Web of Science Citations: 1

Abstract

Neonatal anoxia induces long-term brain injury that may underlie neurobehavioral deficits at adolescence. Neonatal anoxia, induced by exposure of 30-hour old pups to 100% nitrogen, represents a non-invasive and global stimulus, which simulates clinical conditions of human pre-term babies (around 6 gestational months). Previous studies showed that neonatal anoxia induced impairments of spatial memory and altered anxiety-like behaviors in male rats tested at adult age. This study evaluated if neonatal anoxia induces similar behavioral effects in female rats, as compared to males, by testing the animals at adolescence, and also searched for possible cell losses in hippocampal subfields. Results in the Elevated Plus Maze test showed that anoxic females spent proportionally more time within the open arms as compared to anoxic males, suggesting a less anxious-like behavior. In the Morris Water Maze Test, latencies and path lengths of the anoxic subjects were longer as compared to control subjects, thus indicating that anoxia disrupted the cognitive functions required for spatial mapping. In addition, results showed that anoxia-induced disruption was greater in male rats as compared to female rats. Stereological analysis revealed that anoxic male rats exhibited significant cell losses in the dorsal hippocampus dentate gyms and CA1 subfields, but not in CA3-2 subfield. Similar results were observed in the ventral hippocampus, but now with cell loss in the male CA3-2 subfield. There were also significant cell loss differences of anoxic male rats as compared to anoxic female rats. In conclusion, neonatal anoxia induces deleterious and long lasting behavioral and cognitive disruptions, and these effects were stronger in male rats as compared to female rats. These changes are congruent with the pattern of cell losses observed in hippocampal subfields. Together, these results emphasize the relevance of scientific research, aiming at clinical strategies and treatments, consider the sex differential patterns of response to neonatal injury. (AU)

• FAPESP's process: 14/22313-3 - Influence of the absence of maternal melatonin during pregnancy and lactation on neurogenesis and on somatic and sensorimotor development of the offspring.
• Grantee: Lívia Clemente Motta Teixeira
• Support Opportunities: Scholarships in Brazil - Doctorate
• 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
• 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