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The contribution of astrocytic Kir4.1 channels to behavioral impairments in a rat model of autism-like induced by valproic acid prenatal exposure
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Shima Davoudi   , Mona Rahdar , Narges Hosseinmardi , Gila Behzadi , Mahyar Janahmadi |
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Abstract: (251 Views) |
Introduction: Autism spectrum disorder is a developmental disease that affects the communication and behavior of affected individuals and is characterized by a wide variation in the types and severity of symptoms. Interestingly, gain-of-function defects in astrocytic Kir4.1 channels have been detected in children with ASD; however, the pathophysiological mechanisms of Kir4.1 channels underlying the development of ASD have yet to be ascertained. Here, we aim to explore through behavioral assessment the contribution of astrocytic Kir4.1 to the autism-like behaviors induced by prenatal valproic acid exposure.
Methods and Materials: From PND28 to PND35, PA-6 (5µg/ml), a specific Kir4.1 inhibitor, was microinjected into the hippocampus of control and VPA-exposed offspring for 7 successive days before behavioral tests. Then, behavioral assessments, including Crawley’s sociability and preference for social novelty, open field, elevated zero maze, and novel object recognition tests, were performed in order, with a time interval of at least 24 hours between each test from PND35 to PND38.
Results: We found that inhibition of Kir4.1 in the control offspring caused lower social interaction, higher anxiety, and decreased ability to recognize novel objects. Moreover, VPA-exposed offspring treated with PA-6, showed further remarkable behavioral impairments than those detected in the VPA-exposed rats.
Conclusions: The findings revealed that in control rats, inhibition of Kir4.1 channels is associated with behavioral impairments such as those observed in autistic-like offspring. Thus, these channels could be a potential pharmaceutical target for the treatment of behavioral impairments in autism in the future.
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| Keywords: Autism spectrum disorder, Valproic acid, Kir4.1, Anxiety, Novel object recognition |
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Full-Text [PDF 343 kb]
(41 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2024/01/18 | Accepted: 2023/08/23 | Published: 2023/08/23
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