Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and behavior

Takada, Silvia Honda; Motta-Teixeira, Lívia Clemente; Machado-Nils, Aline Vilar; Lee, Vitor Yonamine; Sampaio, Carlos Alberto Cioce; Polli, Roberson Saraiva; Malheiros, Jackeline Moraes; Takase, Luiz Fernando; Kihara, Alexandre Hiroaki; Covolan, Luciene; Xavier, Gilberto Fernando; Nogueira, Maria Inês

doi:10.1016/j.bbr.2015.08.039

Cited by 35 publications

(27 citation statements)

References 55 publications

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“…In accordance with this research, these findings on male rats, has also been reported in other experimental models of neonatal hypoxia‐ischemia (Caputa et al, 2005; Fan et al, 2005; Hei et al, 2012). On the other hand, age impacts on brain functioning, once it was observed in a previous study that the same neonatal anoxia model, at PND 90, decreased the %OAT and the percentage of time spent on the closed arm was significantly higher in adult male subjected to neonatal anoxia than in control animals (Takada et al, 2016) suggesting a long term anxiogenic effect of this stimulus.…”

Section: Discussionmentioning

confidence: 78%

“…Reference and working memory impairments after neonatal hypoxia‐ischemia and anoxia have been previously reported in males (Ikeda et al, 2001; Arteni et al, 2010; Takada et al, 2015; Takada et al, 2016; Huang et al, 2017; Kumar et al, 2017). In the present work, we showed that reference spatial memory is impaired only in the anoxic male rats compared to control subjects, whereas female's performance on this task was unaffected by the same condition.…”

Section: Discussionmentioning

confidence: 83%

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

Kumar

Motta-Teixeira

Takada

et al. 2018

Intl J of Devlp Neuroscience

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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 gyrus 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.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 83%

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

Kumar

Motta-Teixeira

Takada

et al. 2018

Intl J of Devlp Neuroscience

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“…In the current study we investigated the effects of NADA treatment in the model of ANH in rats. The rats were subjected to hypoxia at a brain maturation stage that corresponds to that of humans born prematurely (Takada et al, 2016, 2015). It was demonstrated that the ANH at P2 in rats induces: (1) a significant upregulation of HIF1‐α, GPx2 and GPx4 mRNA expression in rat brains at 1.5 h after hypoxia with normalisation to control values occurring at P6; (2) a sensorimotor impairment in early infancy; (3) a development of hyperreactivity in adolescence and (4) a stress‐induced disruption of memory retention in adulthood.…”

Section: Discussionmentioning

confidence: 99%

“…We may propose that there were no effects of hypoxia on spatial learning due to the short (2 min) intertrial interval. It was shown that neonatal anoxia led to the impairments in the spatial working memory in Morris water maze when intertrial interval was 10, but not 0 min (Takada et al, 2016). However, when we added a new stressful stimulus on 6 th day, the hypoxic animals made more errors than control, confirming deficits in memory retention.…”

Section: Discussionmentioning

confidence: 99%

Early‐life N‐arachidonoyl‐dopamine exposure increases antioxidant capacity of the brain tissues and reduces functional deficits after neonatal hypoxia in rats

Sukhanova

Sebentsova

Khukhareva

et al. 2019

Intl J of Devlp Neuroscience

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Perinatal hypoxia‐ischemia is one of the most common causes of perinatal brain injury and subsequent neurological disorders in children. The aim of this work was to evaluate the potential antioxidant and neuroprotective effects of N‐arachidonoyl‐dopamine (NADA) in the model of acute neonatal hypoxia (ANH) in rat pups. Male and female Wistar rats were exposed to a hypoxic condition (8% oxygen for 120 min) at postnatal day 2 (P2). Transcription factor HIF1‐α and glutathione peroxidases GPx2 and GPx4 gene expression was increased in rat brains in the hypoxic group compared to control 1.5 h but not 4 days after ANH. There were no post‐hypoxic changes in reduced (GSH) and oxidised (GSSG) glutathione levels in the brain of rat pups 1.5 h and 4 d after hypoxia. Hypoxic rats displayed retarded performance in the righting reflex and the negative geotaxis tests. ANH resulted in increased ambulation in Open field test and impaired retention in the Barnes maze task under stressful conditions as compared with the control group. Treatment with NADA significantly attenuated the delayed development of sensorimotor reflexes and stress‐evoked disruption of memory retention in hypoxic rats but had no effect on the hypoxia‐induced hyperactivity. In rats exposed to hypoxia, treatment with NADA decreased GPx2 gene expression and increased GSH/GSSG ratio in whole brains 1.5 h after ANH. These results suggest that the long‐lasting beneficial effects of NADA on hypoxia‐induced neurobehavioural deficits are mediated, at least in part, by its antioxidant properties.

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“…Up to now, stress is the earliest identified and the most profound factor that can affect adult neurogenesis both positively and negatively [4, 5]. In brain, hippocampal area was crucially involved in memory and emotional information processing, which affects the abilities of generating and differentiating into multiple neural cell lineages [6]. A large number of evidences have suggested that hippocampal neurogenesis contributes to some hippocampus-dependent tasks, such as cognition and mood [7].…”

Section: Introductionmentioning

confidence: 99%

Xiao Yao San against Corticosterone-Induced Stress Injury via Upregulating Glucocorticoid Receptor Reaction Element Transcriptional Activity

Cao

Gong

Zhang

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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Previous studies have revealed that uncontrollable stress can impair the synaptic plasticity and firing property of hippocampal neurons, which influenced various hippocampal-dependent tasks including memory, cognition, behavior, and mood. In this work, we had investigated the effects and mechanisms of the Chinese herbal medicine Xiao Yao San (XYS) against corticosterone-induced stress injury in primary hippocampal neurons (PHN) cells. We found that XYS and RU38486 could increase cell viabilities and decrease cell apoptosis by MTT, immunofluorescence, and flow cytometry assays. In addition, we observed that XYS notably inhibited the nuclear translocation of GR and upregulated the mRNA and protein expressions levels of Caveolin-1, GR, BDNF, TrkB, and FKBP4. However, XYS downregulated the FKBP51 expressions. Furthermore, the results of the electrophoretic mobility shift assay (EMSA) and double luciferase reporter gene detection indicated that FKBP4 promotes the transcriptional activity of GR reaction element (GRE) by binding with GR, and FKBP51 processed the opposite action. The in vivo experiment also proved the functions of XYS. These results suggested that XYS showed an efficient neuroprotection against corticosterone-induced stress injury in PHN cells by upregulating GRE transcriptional activity, which should be developed as a potential candidate for treating stress injury in the future.

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Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and behavior

Cited by 35 publications

References 55 publications

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

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

Early‐life N‐arachidonoyl‐dopamine exposure increases antioxidant capacity of the brain tissues and reduces functional deficits after neonatal hypoxia in rats

Xiao Yao San against Corticosterone-Induced Stress Injury via Upregulating Glucocorticoid Receptor Reaction Element Transcriptional Activity

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