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Updated: Jun 27, 2026
Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins
Published on: August 15, 2017
Pannexin1 Mediates Early-Life Seizure-Induced Social Behavior Deficits
Price Obot1, Antonio Cibelli2, Jian Pan1
1Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York, USA.
Insights
Early-life seizures (ELS) in mice lead to lasting social deficits, dependent on Pannexin1 (Panx1) channels. Targeting neuronal Panx1 may mitigate these autism spectrum disorder-like behaviors.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Childhood epilepsy and autism spectrum disorder (ASD) frequently co-occur, with early seizure onset impacting behavioral outcomes.
- Early-life seizures (ELS) in animal models induce adult learning, memory, and autistic-like behaviors, potentially via altered excitation/inhibition balance.
- The role of ATP release channels, specifically Pannexin1 (Panx1), in ELS-induced behavioral changes remains unclear.
Purpose of the Study:
- To investigate the involvement of Pannexin1 (Panx1) channels in behavioral deficits following early-life seizures (ELS).
- To determine if global or cell-type specific deletion of Panx1 affects later-life behavioral outcomes in a mouse model.
Main Methods:
- Utilized the kainic acid-induced early-life seizure (ELS) model in transgenic mice with global and neuronal/astrocyte-specific Pannexin1 (Panx1) deletion.
- Assessed social behavior and spatial memory performance in adult mice subjected to ELS.
Main Results:
- ELS induced social behavior deficits that were dependent on Pannexin1 (Panx1).
- Spatial memory deficits were observed after ELS but were independent of Pannexin1 (Panx1).
- Neuronal Pannexin1 (Panx1), but not astrocyte Panx1, was identified as a key contributor to social deficits and astrogliosis post-ELS.
Conclusions:
- Early-life seizures (ELS) are linked to adult behavioral deficits, including social impairments.
- Neuronal Pannexin1 (Panx1) is a critical mediator of ELS-induced social deficits and astrogliosis.
- Targeting neuronal Pannexin1 presents a potential therapeutic strategy for mitigating behavioral consequences of early-life seizures.
Abstract:
There is a high co-morbidity between childhood epilepsy and autism spectrum disorder (ASD), with age of seizure onset being a critical determinant of behavioral outcomes. The interplay between these comorbidities has been investigated in animal models with results showing that the induction of seizures at early post-natal ages leads to learning and memory deficits and to autistic-like behavior in adulthood. Modifications of the excitation/inhibition (glutamate/GABA, ATP/adenosine) balance that follows early-life seizures (ELS) are thought to be the physiological events that underlie neuropsychiatric and neurodevelopmental disorders. Although alterations in purinergic/adenosinergic signaling have been implicated in seizures and ASD, it is unknown whether the ATP release channels, Pannexin1 (Panx1), contribute to ELS-induced behavior changes. To tackle this question, we used the ELS-kainic acid model in transgenic mice with global and cell type specific deletion of Panx1 to evaluate whether these channels were involved in behavioral deficits that occur later in life. Our studies show that ELS results in Panx1 dependent social behavior deficits and also in poor performance in a spatial memory test that does not involve Panx1. These findings provide support for a link between ELS and adult behavioral deficits. Moreover, we identify neuronal and not astrocyte Panx1 as a potential target to specifically limit astrogliosis and social behavioral deficits resultant from early-life seizures.
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