Histamine H3 receptor antagonist, ciproxifan, alleviates cognition and synaptic plasticity alterations in a valproic acid-induced animal model of autism

Taheri, Farahnaz; Esmaeilpour, Khadijeh; Sepehri, Gholamreza; Sheibani, Vahid; Rehman, Naeem Ur; Maneshian, Marzieh

doi:10.1007/s00213-022-06155-z

Cited by 12 publications

(40 citation statements)

References 95 publications

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Section: Introductionmentioning

confidence: 73%

“…Animal studies have also reported social interaction deficits (Sabzalizadeh et al, 2022;Taheri et al, 2022) and increased repetitive behaviors in VPA-exposed animals (Baronio et al, 2015;Eissa et al, 2018b). Our previous study showed social deficits in adult VPA-exposed rats (Taheri et al, 2022). Additionally, prenatal VPA caused increased anxiety in mice, as indicated by a significant decrease in the number of rearing and the frequency of entries into the center field during an open-field task (Yamaguchi et al, 2017;Gao et al, 2019).…”

Section: Introductionmentioning

confidence: 85%

“…Pregnant rats were randomly divided into two groups. VPA: Pregnant rats received an intraperitoneal injection of 600 mg/kg VPA which was diluted with normal saline to a concentration of 200 mg/mL at embryonic day 12.5 (E12.5) (Taheri et al, 2022). Saline: Pregnant rats received an intraperitoneal injection of saline at E12.5.…”

Section: Pregnancy Determinationmentioning

confidence: 99%

“…The pharmaceutical company, SMS Life Sciences India Limited, prepared FAM. The drugs were dissolved in normal saline, with the exception of FAM, which was dissolved in one drop of 1 M hydrochloric acid and then diluted in normal saline (Taheri et al, 2022). The solutions were freshly prepared daily.…”

Section: Drugsmentioning

confidence: 99%

“…Several studies have focused on the various brain neurotransmitters such as histamine and their influence on behavior in brain disorders (Alhusaini et al, 2022;Taheri et al, 2022). Histamine plays a significant role in basic physiological functions such as sleep-wake cycles, sensory and motor functions, cognition, and attention, all of which are severely affected in neuropsychiatric disorders (Sadek et al, 2016a).…”

Section: Introductionmentioning

confidence: 99%

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Amelioration of cognition impairments in the valproic acid-induced animal model of autism by ciproxifan, a histamine H3-receptor antagonist

Taheri

Esmaeilpour

Sepehri

et al. 2023

Behavioural Pharmacology

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Autism spectrum disorder is a neurodevelopmental disorder characterized by deficits in social communication and repetitive behavior. Many studies show that the number of cognitive impairmentscan be reduced by antagonists of the histamine H3 receptor (H3R). In this study, the effects of ciproxifan (CPX) (1 and 3 mg/kg, intraperitoneally) on cognitive impairments in rat pups exposed to valproic acid (VPA) (600 mg/kg, intraperitoneally) wereexamined on postnatal day 48–50 (PND 48–50) using marble-burying task (MBT), open field, novel object recognition (NOR), and Passive avoidance tasks. Famotidine (FAM) (10, 20, and 40 mg/kg, intraperitoneally) was also used to determine whether histaminergic neurotransmission exerts its procognitive effects via H2 receptors (H2Rs). Furthermore, a histological investigation was conducted to assess the degree of degeneration of hippocampal neurons. The results revealed that repetitive behaviors increased in VPA-exposed rat offspring in the MBT. In addition, VPA-exposed rat offspring exhibited more anxiety-like behaviors in the open field than saline-treated rats. It was found that VPA-exposed rat offspring showed memory deficits in NOR and Passive avoidance tasks. Our results indicated that 3 mg/kg CPX improved cognitive impairments induced by VPA, while 20 mg/kg FAM attenuated them. We concluded that 3 mg/kg CPX improved VPA-induced cognitive impairments through H3Rs. The histological assessment showed that the number of CA1 neurons decreased in the VPA-exposed rat offspring compared to the saline-exposed rat offspring, but this decrease was not significant. The histological assessment also revealed no significant differences in CA1 neurons in VPA-exposed rat offspring compared to saline-exposed rat offspring. However, CPX3 increased the number of CA1 neurons in the VPA + CPX3 group compared to the VPA + Saline group, but this increase was not significant. This study showed that rats prenatally exposed to VPA exhibit cognitive impairments in the MBT, open field, NOR, and Passive avoidance tests, which are ameliorated by CPX treatment on PND 48–50. In addition, morphological investigations showed that VPA treatment did not lead to neuronal degeneration in the CA1 subfield of the hippocampus in rat pups.

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Section: Introductionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 85%

Section: Pregnancy Determinationmentioning

confidence: 99%

Section: Drugsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Amelioration of cognition impairments in the valproic acid-induced animal model of autism by ciproxifan, a histamine H3-receptor antagonist

Taheri

Esmaeilpour

Sepehri

et al. 2023

Behavioural Pharmacology

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Effects of music on cognitive behavioral impairments in both sex of adult rats exposed prenatally to valproic acid

Taheri,

Joushi,

Mohammadipoor‐Ghasemabad

et al. 2024

Birth Defects Research

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BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive behaviors and interests. In previous studies, music has been identified as an intervention therapy for children with ASD.ObjectivesThe present study evaluated the effects of music on cognitive behavioral impairments in both sexes of adult rats exposed prenatally to Valproic acid.MethodsFor induction of autism, pregnant female rats were pretreated with either saline or VPA (600 mg/kg.i.p.) at gestational day (GD) 12.5. Male and female offspring were divided into Saline.Non‐Music, VPA.Non‐Music, Saline.Music, and VPA.Music groups. The adult rats in the music groups were exposed to Mozart's piano sonata K.448 for 30 days (4 h/day), from postnatal day (PND) 60 to 90. Social interaction and Morris water maze (MWM) tasks were tested at PND 90.ResultsOur results revealed that prenatal exposure to VPA decreased sociability and social memory performance in both sexes of adult rats. Moreover, prenatal exposure to VPA created learning and memory impairments in both sexes of adult rats in the MWM task. Music intervention improved sociability in both sexes of VPA‐exposed rats and social memory in both sexes of VPA‐exposed rats, especially in females. Furthermore, our results revealed that music ameliorated learning impairments in VPA‐exposed female rats in the MWM task. In addition, music improved spatial memory impairments in VPA‐exposed rats of both sexes, especially in females, which needs more investigation in molecular and histological fields in future studies.ConclusionMusic intervention improved sociability and social memory in adult VPA‐exposed rats, especially in female animals. Furthermore, music improved memory impairments in VPA‐exposed rats of both sexes. It seems that music had a better influence on female rats. However, future studies need more investigations in molecular and histological fields.

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Transmission of behavioral and cognitive impairments across generations in rats subjected to prenatal valproic acid exposure

Taheri,

Joushi,

Esmaeilpour

et al. 2024

Birth Defects Research

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BackgroundAutism spectrum disorder (ASD) represents an inheritable neurodevelopmental condition characterized by social communication deficits and repetitive behaviors. Numerous studies have underscored the significant roles played by genetic and environmental factors in the etiology of ASD, and these factors are known to perpetuate behavioral impairments across generations.ObjectivesThe primary objective of this study was to assess the behavioral and cognitive attributes in the second filial (F2) generation of male and female rats, with a particular focus on those whose parents had been exposed to valproic acid (VPA) during embryonic development.MethodsIn this study, a cohort of 32 male and 32 female rats from the second filial (F2) generation, referred to as Mother.ASD, Father.ASD, or Both.ASD, was examined. These designations indicate whether the mother, father, or both parents had experienced embryonic exposure to valproic acid (600 mg/kg, i.p.). During adolescence, the F2 pups underwent behavioral and cognitive assessments, including open field testing, marble burying, social interaction evaluations, and Morris water maze tasks.ResultsOur data revealed that while both the Mother.ASD and Father.ASD groups, regardless of sex, exhibited elevated anxiety‐like behavior in the open field test. Only the Mother.ASD group displayed repetitive behaviors and deficits in social memory. Additionally, spatial memory impairments were observed in both sexes. These findings highlight the transmission of autistic‐like behaviors in the offspring of Mother.ASD rats from both sexes. Nevertheless, future research endeavors should be more targeted in identifying the specific genes responsible for this transmission.ConclusionIn summary, our findings underscore the transmission of autistic‐like behaviors, including anxiety‐like behavior, repetitive actions, impairments in social interactions, and deficits in memory, to the offspring of the Mother.ASD group, irrespective of their sex.

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Histamine H3 receptor antagonist, ciproxifan, alleviates cognition and synaptic plasticity alterations in a valproic acid-induced animal model of autism

Cited by 12 publications

References 95 publications

Amelioration of cognition impairments in the valproic acid-induced animal model of autism by ciproxifan, a histamine H3-receptor antagonist

Amelioration of cognition impairments in the valproic acid-induced animal model of autism by ciproxifan, a histamine H3-receptor antagonist

Effects of music on cognitive behavioral impairments in both sex of adult rats exposed prenatally to valproic acid

Transmission of behavioral and cognitive impairments across generations in rats subjected to prenatal valproic acid exposure

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