Validation of prenatal versus postnatal valproic acid rat models of autism: A behavioral and neurobiological study

Elnahas, Esraa M.; Abuelezz, Sally A.; Mohamad, Magda I.; Nabil, Mai M.; Abdelraouf, Sahar M.; Bahaa, Nevine; Hassan, Ghada A.M.; Ibrahim, Eman; Ahmed, Asmaa Ibrahim; Aboul‐Fotouh, Sawsan

doi:10.1016/j.pnpbp.2020.110185

Cited by 34 publications

(14 citation statements)

References 59 publications

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“…1d) (Pragnya et al, 2014). In accordance with previous reports, cerebellar and hippocampus damage may cause motor dysfunction, anxiety, learning and social deficits (Mirza and Sharma, 2019;Edalatmanesh et al, 2013;Elnahas et al, 2021). As establish a correlation between various behavioural tasks involving mainly the cerebellar and hippocampal regions of the brain in the Balb/C mice challenged with sodium valproate.…”

Section: Morris Water Maze For Learning and Memorysupporting

confidence: 87%

“…Autism Spectrum Disorder (ASD) is attributable to dysfunction of neurotransmitter system, which alters neuronal cell migration, differentiation, and synaptogenesis and the overall developmental processes of the brain (Cetin et al, 2015). Alterations in GAB Anergic, glutamatergic, and serotonergic reported earlier by Rice and Barone (2000), Pragnya et al (2014) and Elnahas et al (2021), the first 3 weeks of postnatal period are essential for the development of motor organization.…”

Section: Morris Water Maze For Learning and Memorymentioning

confidence: 99%

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Correlation studies on pathological changes in brain with neurotransmitters and behavioural changes in Balb/c mice

Balaji¹,

Sinha²,

Mullapudi³

et al. 2022

JEB

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Aim: To determine the plasma neurotransmitters simultaneously and to find any correlation with pathological changes in the hippocampus and Purkinje cells and their relation with behavioral changes in Balb/c mice. Methodology: In the present study, both sexes of Balb /C mice were divided into two groups (4 males and 4 females; n = 8): Both the groups were given a single dose of either saline or sodium valproate (400mg kg-1) respectively through subcutaneous injection on PND 14. Behavioural tests were conducted on mice pups on various postnatal days till 40th day. On PND 41, blood samples were collected from all the animals for quantification of the neurotransmitters (serotonin, dopamine, and noradrenalin) in plasma, animals were sacrificed by cervical dislocation and whole brain was isolated for histological examination of the Purkinje cells and hippocampus. Results: Sodium valproate exposed animals showed loss of motor skill development (delayed negative geotaxic response), increased locomotor activity, increased anxiety, and retardation in water maze performance, and lower social interaction. Histopathological evolutions of cerebellum purkinje cells and hippocampus showed 40-50% atrophic cells in sodium valproate animals compared to control animals. Interpretation: The results of the present study indicate that Sodium valproate changes specific brain cell population in Balb/C mice, which might be the reason for the altered neurotransmitter levels, leading to behavioural changes in these animals.

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Section: Morris Water Maze For Learning and Memorysupporting

confidence: 87%

Section: Morris Water Maze For Learning and Memorymentioning

confidence: 99%

Correlation studies on pathological changes in brain with neurotransmitters and behavioural changes in Balb/c mice

Balaji¹,

Sinha²,

Mullapudi³

et al. 2022

JEB

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“…19,45,46 Prenatal exposure to valproic acid has been known to cause ASD-like behaviors (eg, impaired social interaction and repetitive behavior) and neurodevelopmental delay in rat offspring. 47,48 In this animal model, maternal folate supplementation prevented development of the ASD-like behaviors in rats prenatally exposed with valproate. 48 Therefore, folate deficiency during periconception and pregnancy is likely involved in occurrence of ASD in offspring.…”

Section: Discussionmentioning

confidence: 92%

“…Folate supplementation during preconception or pregnancy has been known to reduce risk of offspring to develop ASD in humans 19,45,46 . Prenatal exposure to valproic acid has been known to cause ASD‐like behaviors (eg, impaired social interaction and repetitive behavior) and neurodevelopmental delay in rat offspring 47,48 . In this animal model, maternal folate supplementation prevented development of the ASD‐like behaviors in rats prenatally exposed with valproate 48 .…”

Section: Discussionmentioning

confidence: 95%

Prenatal methotrexate injection increases behaviors possibly associated with depression and/or autism in rat offspring; A new animal model for mental disorder, based on folate metabolism deficit during pregnancy

Amada

Kakumoto

Futamura

et al. 2022

Neuropsychopharm Rep

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Background: Deficiency of folate, an essential vitamin for DNA synthesis and methylation, is reported as a risk factor for mental disorders. Considering a possibility that folate metabolism deficit during pregnancy may disturb CNS development and increase mental disorders in offspring, we treated pregnant rats with methotrexate (MTX), an inhibitor of folate metabolic enzyme, and evaluated offspring behaviors. Methods: Saline or MTX was intraperitoneally administered to female SD rats on gestational day 17. Offspring behaviors were evaluated during approximately 6-9 weeks old; prepulse inhibition (PPI), social interaction (SI), locomotor activity (LA), and forced swimming test (FST) for evaluation of schizophrenia, depression, and autism related behaviors; the elevated plus maze (EPM) and the light-dark box (LD) test for evaluation of anxiety. Results: Compared to saline-treated group, MTX-treated group showed decrease of SI and increase of immobility time in FST. In addition, increases of time spent in the light box and shuttling between the light-dark boxes were observed in LD test. On the other hand, no changes were confirmed in EPM, LA, and PPI. Conclusion: Decrease of SI and increase of immobility time in FST may suggest association of this animal model with depression and/or autism. Increase of time spent in the light box and shuttling between the light-dark boxes may indicate changes in anxiety or cognitive level to environment, or repetitive behaviors in autism. Although further studies are warranted to characterize this animal model, at least we can say that prenatal MTX exposure, possibly causing folate metabolism deficit, affects offspring behaviors.

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“…In animal experiments, researchers have simulated typical ASD models of newborn mice by exposing female mice to VPA during pregnancy. Prenatal and postnatal VPA exposure in mice can induce autism-like behaviors, and inflammatory cytokines and oxidative/nitrosative stress markers in the prefrontal cortex and hippocampal homogenate are increased in VPA-treated offspring ( Elnahas et al, 2021 ). The degree of neuropathological changes depends on the dose and duration of VPA exposure ( Bringas et al, 2013 ).…”

Section: Diverse Animal Models Exploring Key Features Of Asdmentioning

confidence: 99%

Understanding autism spectrum disorders with animal models: applications, insights, and perspectives

Zhu

et al. 2021

Zoological Research

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Autism spectrum disorder (ASD) is typically characterized by common deficits in social skills and repetitive/stereotyped behaviors. It is widely accepted that genetic and environmental factors solely or in combination cause ASD. However, the underlying pathogenic mechanism is unclear due to its highly heterogeneous nature. To better understand the pathogenesis of ASD, various animal models have been generated, which can be generally divided into genetic, environment-induced, and idiopathic animal models. In this review, we summarize the common animals used for ASD study and then discuss the applications, clinical insights, as well as challenges and prospects of current ASD animal models.

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Validation of prenatal versus postnatal valproic acid rat models of autism: A behavioral and neurobiological study

Cited by 34 publications

References 59 publications

Correlation studies on pathological changes in brain with neurotransmitters and behavioural changes in Balb/c mice

Correlation studies on pathological changes in brain with neurotransmitters and behavioural changes in Balb/c mice

Prenatal methotrexate injection increases behaviors possibly associated with depression and/or autism in rat offspring; A new animal model for mental disorder, based on folate metabolism deficit during pregnancy

Understanding autism spectrum disorders with animal models: applications, insights, and perspectives

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