Risperidone and aripiprazole alleviate prenatal valproic acid-induced abnormalities in behaviors and dendritic spine density in mice

Hara, Yuta; Ago, Yukio; Taruta, Atsuki; Hasebe, Shigeru; Kawase, Haruki; Tanabe, Wataru; Tsukada, Shinji; Nakazawa, Takahiro; Hashimoto, Hitoshi; Matsuda, Takehisa; Takuma, Kazuhiro

doi:10.1007/s00213-017-4703-9

Cited by 39 publications

(25 citation statements)

References 52 publications

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“…Notably, Hara et al ( 2016 ) found that inhibition of DAT by atomoxetine and methylphenidate has beneficial effects on VPA-induced ASD phenotypes, but not on NET (Hara et al, 2016 ). These findings are consistent with there being increased extracellular dopamine levels in the prefrontal cortex of VPA-induced ASD animal models after chronic risperidone treatments (Hara et al, 2017 ).…”

Section: Dysregulation Of Monoamine Transmission In Asdsupporting

confidence: 84%

“…Chronic treatments with 8-OH-DPAT, a 5-HT 1A receptor agonist, not only ameliorates fear memory extinction and social impairment, but also normalizes the E/I balance within the amygdala (Wang et al, 2013 ). Hara et al ( 2017 ) found that aripiprazole (an atypical antipsychotics that acts as a 5-HT 1A receptor agonist and a partial agonist of D2R in order to reduce DA transmission) and risperidone (an atypical antipsychotics that inhibits D2R and the 5-HT 2A receptor), but not haloperidol, are able to alleviate reverse recognition memory deficits and social impairment of VPA-treated rats, as well as restoring the reduced number of dendritic spines in the mPFC of VPA-treated rats (Hara et al, 2017 ). Abnormal vocal communication and striatal compartmentation in VPA-treated mouse neonates are also partially rescued by chronic risperidone treatment after birth (Kuo and Liu, 2017 ).…”

Section: Dysregulation Of Monoamine Transmission In Asdmentioning

confidence: 99%

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Molecular Pathology and Pharmacological Treatment of Autism Spectrum Disorder-Like Phenotypes Using Rodent Models

Kuo¹,

Liu²

2018

Front. Cell. Neurosci.

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Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder with a high prevalence rate. The core symptoms of ASD patients are impaired social communication and repetitive behavior. Genetic and environmental factors contribute to pathophysiology of ASD. Regarding environmental risk factors, it is known that valproic acid (VPA) exposure during pregnancy increases the chance of ASD among offspring. Over a decade of animal model studies have shown that maternal treatment with VPA in rodents recapitulates ASD-like pathophysiology at a molecular, cellular and behavioral level. Here, we review the prevailing theories of ASD pathogenesis, including excitatory/inhibitory imbalance, neurotransmitter dysfunction, dysfunction of mTOR and endocannabinoid signaling pathways, neuroinflammation and epigenetic alterations that have been associated with ASD. We also describe the evidence linking neuropathological changes to ASD-like behavioral abnormalities in maternal VPA-treated rodents. In addition to obtaining an understanding of the neuropathological mechanisms, the VPA-induced ASD-like animal models also serve as a good platform for testing pharmacological reagents that might be use treating ASD. We therefore have summarized the various pharmacological studies that have targeted the classical neurotransmitter systems, the endocannabinoids, the Wnt signal pathway and neuroinflammation. These approaches have been shown to often be able to ameliorate the ASD-like phenotypes induced by maternal VPA treatments.

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Section: Dysregulation Of Monoamine Transmission In Asdsupporting

confidence: 84%

Section: Dysregulation Of Monoamine Transmission In Asdmentioning

confidence: 99%

Molecular Pathology and Pharmacological Treatment of Autism Spectrum Disorder-Like Phenotypes Using Rodent Models

Kuo¹,

Liu²

2018

Front. Cell. Neurosci.

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“…Importantly, pre-registering studies would further separate pre-diction and post-diction analyses to better delineate the relationship between hypothesis and results, and to better compare different results [73,74]. As noticed in the therapeutic studies (Table 4), a publication bias appears to exist, whereby only successful treatments have generally been published, whereas unsuccessful treatment trials have not been reported (with the exception of haloperidol [75]).…”

Section: Effectiveness Of Novel Pharmacotherapies In the Vpa Model Anmentioning

confidence: 99%

A Systematic Review of the Valproic-Acid-Induced Rodent Model of Autism

et al. 2020

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by repetitive behaviours, cognitive rigidity/inflexibility, and social-affective impairment. Unfortunately, few pharmacological treatments exist to alleviate these socio-behavioural impairments. Prenatal administration of valproic acid (VPA) has become an accepted animal model of ASD and has been extensively used to explore new pharmacotherapies in rodents. We conducted a systematic review of the behavioural impairments induced by the VPA model in rodents, with specific reference to 3 core socio-behavioural alterations associated with ASD: repetitive behaviours, cognitive rigidity/inflexibility, and social-affective impairment. We systematically reviewed studies attempting to alleviate these core behavioural alterations using pharmacological means. We include 132 studies exploring the prenatal effects of VPA in rodents. Gestational exposure to VPA in rodents has significant effects on rodent-equivalent measures of the 3 core behavioural traits characteristic of ASD in humans, inducing social impairments, repetitive behaviour, and cognitive rigidity/inflexibility after birth. This model's validity has seen it used to test potential drug treatments for ASD and is likely to continue doing so. We conclude the rodent VPA model may be suitable to examine future therapeutic interventions for ASD, providing an overview of the progress made so far.

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“…HRW (H 2 concentration >1.8 mg/L, 245 mL) generously provided by Beijing Hydrovita Beverage Co. Limited (Beijing, China) and stowed at ambient pressure and temperature in an aluminum can with no head space. VPA (purchased from Sigma-Aldrich, Shanghai, China) was used following the procedure of previous reports to induce autistic-like behavior in mice (Al-Amin et al, 2015 ; Hara et al, 2017 ; Yamaguchi et al, 2017 ). VPA was dissolved in 0.9% NaCl solution, and the volume of injection was 10 mL/kg.…”

Section: Methodsmentioning

confidence: 99%

Hydrogen-Rich Water Ameliorates Autistic-Like Behavioral Abnormalities in Valproic Acid-Treated Adolescent Mice Offspring

Guo

Yin

Qiao

et al. 2018

Front. Behav. Neurosci.

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Due to its anti-inflammatory and anti-oxidative effects, recent research has demonstrated that molecular hydrogen can serve as a new medical approach for depression, anxiety and traumatic brain injury. However, its potential effects on neurodevelopmental diseases, such as autism are still elusive. The present study aims to investigate the potential effects of hydrogen-rich water (HRW) administration on valproic acid (VPA)-induced autistic-like behavioral deficits, and the associated underlying mechanism in adolescent mice offspring. Pregnant ICR mice were randomly divided into five groups (n = 6). One group was injected with saline (NAV group) and provided hydrogen-free water. The other four groups were injected with VPA (600 mg/kg, intraperitoneally, i.p.) on pregnant day (PND) 12.5. One group was provided with hydrogen-free water (VEH group) and the other three groups were provided HRW at different segments, postnatal day 1 (PND 1) to PND 21 (PHV group), PND 13 to PND 21 (PVS group) or from PND 13 to postnatal day 42 (PVL group). Behavioral tests, including open field, novelty suppressed feeding (NSF), hot plate, social interaction (SI) and contextual fear memory tests were conducted between postnatal day 35–42. We found that HRW administration significantly reversed the autistic-like behaviors induced by maternal VPA exposure in the adolescent offspring of both male and female adolescent offspring. Furthermore, HRW administration significantly reversed the alternation of serum levels of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), but without any effects on the BDNF levels in maternal VPA-exposed mice offspring. These data suggest the need for additional research on HRW as a potential preventive strategy for autism and related disorders.Lay Summary: Maternal VPA injection induces autistic-like behavioral deficits in adolescent mice offspring. HRW administration ameliorates autistic-like behavioral deficits. HRW administration reverses the alternation of serum levels of IL-6 and TNF-α induced by VPA.

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Risperidone and aripiprazole alleviate prenatal valproic acid-induced abnormalities in behaviors and dendritic spine density in mice

Cited by 39 publications

References 52 publications

Molecular Pathology and Pharmacological Treatment of Autism Spectrum Disorder-Like Phenotypes Using Rodent Models

Molecular Pathology and Pharmacological Treatment of Autism Spectrum Disorder-Like Phenotypes Using Rodent Models

A Systematic Review of the Valproic-Acid-Induced Rodent Model of Autism

Hydrogen-Rich Water Ameliorates Autistic-Like Behavioral Abnormalities in Valproic Acid-Treated Adolescent Mice Offspring

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