Hyperexcitability of hippocampal CA1 pyramidal neurons in male offspring of a rat model of autism spectrum disorder (ASD) induced by prenatal exposure to valproic acid: A possible involvement of Ih channel current

Hajisoltani, Razieh; Karimi, Seyed Asaad; Rahdar, Mona; Davoudi, Shima; Borjkhani, Mehdi; Hosseinmardi, Narges; Behzadi, Gila; Janahmadi, Mahyar

doi:10.1016/j.brainres.2018.12.011

Cited by 34 publications

(26 citation statements)

References 69 publications

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“…Recent studies of several neuropsychiatric disorders, including ASDs and their animal models, have led to the hypothesis that social and communication deficits are associated with neuronal hyperexcitability in the hippocampal CA1 pyramidal neurons 15,41,42 . Despite this association between CA1 and social deficits, the underlying disturbances in the CA1 region remain largely unexplored.…”

Section: Discussionmentioning

confidence: 99%

“…To determine the impacts of PRMT7 deletion on behaviors, we subjected the PRMT7 KO mice to a battery of behavioral tests. Because PRMT7 is highly expressed in the hippocampal CA1 region and has been shown to be associated with ASDs and depression 15,33 , we first tested whether the PRMT7 KO mice displayed social deficits. To assess the social interaction of the PRMT7 KO mice, we utilized the three-chamber social approach test, which has been extensively used in studies of sociality with various mouse lines 34 .…”

Section: The Prmt7 Ko Mice Show Impaired Social Behaviormentioning

confidence: 99%

“…The hippocampal CA1 region stores social memory, and dysfunction of the CA1 pyramidal neurons has been associated with impairments in social interactions and ASDs 15,33 . To identify the neural mechanisms underlying the impaired social interaction in the PRMT7 KO mice, we performed electrophysiological recordings of the CA1 pyramidal cells from the hippocampal slices obtained from the WT and KO mice.…”

Section: Enhanced Excitability and Input Resistance Of The Ca1 Pyramimentioning

confidence: 99%

“…Kim and colleagues 14 showed that HCN1 in CA1 was increased with chronic mild stress and that short hairpin RNA (shRNA) knockdown of HCN1 in CA1 led to a reduction in anhedonia-like behavior and an increase in antidepressantlike behavior. In addition, hyperexcitability of the hippocampal CA1 pyramidal neurons was observed in a rat model of autism spectrum disorders (ASDs) 15 . Furthermore, autism-associated SHANK3 haploinsufficiency causes I h channelopathy in hippocampal neurons 16 .…”

Section: Introductionmentioning

confidence: 99%

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PRMT7 deficiency causes dysregulation of the HCN channels in the CA1 pyramidal cells and impairment of social behaviors

Lee

Vuong

et al. 2020

Exp Mol Med

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HCN channels regulate excitability and rhythmicity in the hippocampal CA1 pyramidal cells. Perturbation in the HCN channel current (I h ) is associated with neuropsychiatric disorders, such as autism spectrum disorders. Recently, protein arginine methyltransferase 7 (PRMT7) was shown to be highly expressed in the hippocampus, including the CA1 region. However, the physiological function of PRMT7 in the CA1 neurons and the relationship to psychiatric disorders are unclear. Here we showed that PRMT7 knockout (KO) mice exhibit hyperactivity and deficits in social interaction. The firing frequency of the CA1 neurons in the PRMT7 KO mice was significantly higher than that in the wild-type (WT) mice. Compared with the WT CA1 neurons, the PRMT7 KO CA1 neurons showed a more hyperpolarized resting potential and a higher input resistance, which were occluded by the I h -current inhibitor ZD7288; these findings were consistent with the decreased I h and suggested the contribution of I h -channel dysfunction to the PRMT7 KO phenotypes. The HCN1 protein level was decreased in the CA1 region of the PRMT7 KO mice in conjunction with a decrease in the expression of Shank3, which encodes a core scaffolding protein for HCN channel proteins. A brief application of the PRMT7 inhibitor DS437 did not reproduce the phenotype of the PRMT7 KO neurons, further indicating that PRMT7 regulates I h by controlling the channel number rather than the open probability. Moreover, shRNA-mediated PRMT7 suppression reduced both the mRNA and protein levels of SHANK3, implying that PRMT7 deficiency might be responsible for the decrease in the HCN protein levels by altering Shank3 expression. These findings reveal a key role for PRMT7 in the regulation of HCN channel density in the CA1 pyramidal cells that may be amenable to pharmacological intervention for neuropsychiatric disorders.

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Section: Discussionmentioning

confidence: 99%

Section: The Prmt7 Ko Mice Show Impaired Social Behaviormentioning

confidence: 99%

Section: Enhanced Excitability and Input Resistance Of The Ca1 Pyramimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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PRMT7 deficiency causes dysregulation of the HCN channels in the CA1 pyramidal cells and impairment of social behaviors

Lee

Vuong

et al. 2020

Exp Mol Med

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“…Apparatus MWM task is a hippocampal-dependent test of spatial learning for rodents (37,38).The water maze apparatus consisted of a black-painted circular pool, (155 cm diameter, 60 cm height), filled to a depth of 35 cm with water (22 ± 1°C). The pool was divided into four equal quadrants.…”

Section: Morris Water Maze (Mwm) Taskmentioning

confidence: 99%

Effects of post-training administration of LY341495, as a mGluR2/3 antagonist on spatial memory deficit in rats fed with high-fat diet

Moridi

Sarihi

Habibitabar

et al. 2020

Preprint

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Background High-fat diets (HFDs) adversely influence glutamate metabolism and neurotransmission. The precise role of the group II metabotropic glutamate receptors (mGluR2/3) antagonist on spatial memory deficit following consumption of HFD has not yet been clarified. Therefore, in this study, we examined the effects of post-training administration of mGluR2/3 antagonism; LY341495 on spatial memory in rats fed with HFD by using Morris Water Maze (MWM) task. Intraperitoneal injection (i.p) injection of LY341495 was done 30 minutes before retention test. Results Our results showed that HFD did not have any effect on memory acquisition. There were not significant differences in escape latency and swimming distance between experimental groups (P>0.05, Two-way ANOVA). Our finding showed that consumption of an HFD leads to spatial memory impairment. There were significant differences in time spent in target zone between experimental groups [F (3, 20) = 7.031, P=0.0021, one-way ANOVA]. Also, LY341495 improved HFD-induced reference memory impairment. HFD animals treated with LY341495 spent more time in the target zone in compare with HFD animals (P= 0.0449). Conclusions Our results suggested that prolonged consumption of high-fat diet has no effects on the acquisition of spatial learning, but can impair memory retention of the adult male rats and post-training administration of LY341495 can improve HFD-induced reference memory impairment.

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Prangos ferulacea (L.) ameliorates behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid

Saadat,

Taherian,

Aldaghi

et al. 2023

Brain and Behavior

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BackgroundPrenatal exposure to valproic acid (VPA) may enhance the risk of autism spectrum disorder (ASD) in children. This study investigated the effect of Prangos ferulacea (L.) on behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid.MethodsPregnant rats received VPA (600 mg/kg, intraperitoneally [i.p.]) or saline on gestational day 12.5 (E 12.5). Starting from the 30th postnatal day (PND 30), the pups were i.p. administered Prangos ferulacea (PF, 100 and 200 mg/kg), or the vehicle, daily until PND 58. On PND 30 and 58, various behavioral tasks were used to evaluate pups, including the open field, elevated plus‐maze, hot‐plate, and rotarod test. On PND 65, the animals were euthanized, and their brains were removed for histopathological and biochemical assay.ResultsPrenatal exposure to VPA caused significant behavioral changes in the offspring, reversed by administering an extract of Prangos ferulacea (L.). Additionally, prenatal VPA administration resulted in increased levels of malondialdehyde and deficits in antioxidant enzyme activities in the hippocampus, including catalase and glutathione, ameliorated by PF. Likewise, postnatal treatment with PF improved VPA‐induced dysregulation of Bax and Blc2 in the hippocampus and reduced neuronal death in CA1, CA3, and dentate gyrus.ConclusionThe findings of this study suggest that postnatal administration of PF can prevent VPA‐induced ASD‐like behaviors by exhibiting antiapoptotic and antioxidant properties. Therefore, PF may have the potential as an adjunct in the management of ASD.

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Hyperexcitability of hippocampal CA1 pyramidal neurons in male offspring of a rat model of autism spectrum disorder (ASD) induced by prenatal exposure to valproic acid: A possible involvement of Ih channel current

Cited by 34 publications

References 69 publications

PRMT7 deficiency causes dysregulation of the HCN channels in the CA1 pyramidal cells and impairment of social behaviors

PRMT7 deficiency causes dysregulation of the HCN channels in the CA1 pyramidal cells and impairment of social behaviors

Effects of post-training administration of LY341495, as a mGluR2/3 antagonist on spatial memory deficit in rats fed with high-fat diet

Prangos ferulacea (L.) ameliorates behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid

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