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Updated: Apr 16, 2026
Strategies for Assessing Autistic-Like Behaviors in Mice
Published on: September 20, 2024
Sera from children with autism induce autistic features which can be rescued with a CNTF small peptide mimetic in
Syed Faraz Kazim1, Maria Del Carmen Cardenas-Aguayo2, Mohammad Arif2
1Inge Grundke-Iqbal Research Floor, Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities (NYSIBR), Staten Island, New York, United States of America; Neural and Behavioral Science Graduate Program, State University of New York (SUNY) Downstate Medical Center, Brooklyn, New York, United States of America; SUNY Downstate/NYSIBR Center for Developmental Neuroscience (CDN), Staten Island, New York, United States of America.
Insights
Autism sera from children induced neurotoxicity and oxidative stress in neurons. A peptide mimetic, Peptide 6 (P6), reversed these effects and autism-like behaviors in rats, suggesting a therapeutic potential.
Area of Science:
- Neuroscience
- Developmental Biology
- Autism Spectrum Disorder Research
Background:
- Autism Spectrum Disorder (ASD) is a neurodevelopmental condition linked to early brain environment alterations.
- Imbalances in neurotrophic support are hypothesized to contribute to ASD pathophysiology.
- Neurotrophic factors play critical roles in neuronal development and survival.
Purpose of the Study:
- To investigate the neurotoxic effects of sera from children with autism on neuronal cells.
- To evaluate the potential of Peptide 6 (P6) as a therapeutic agent for autism-related neurotoxicity and behavioral deficits.
- To explore the role of neurotrophic factor imbalance in early brain development and its connection to autism.
Main Methods:
- Exposure of mouse primary cortical neurons to sera from children with autism.
- Treatment of neurons with Peptide 6 (P6), a ciliary neurotrophic factor (CNTF) mimetic.
- Intracerebroventricular injection of autism sera into neonatal Wistar rats.
- Assessment of neurobiological changes (cell death, oxidative stress, neuroinflammation) and behavioral phenotypes in rats.
Main Results:
- Sera from children with autism induced neuronal cell death and oxidative stress.
- Pre-treatment with P6 rescued neurons from autism sera-induced toxicity.
- Rats injected with autism sera exhibited developmental delays, social deficits, and neuroinflammation.
- P6 treatment ameliorated both the neurobiological changes and the autistic behavioral phenotype in rats.
Conclusions:
- Neurotrophic factor imbalance during early brain development is implicated in autism pathophysiology.
- Peptide 6 (P6) demonstrates neuroprotective effects against autism-associated neurotoxicity.
- P6 shows promise as a potential therapeutic strategy for addressing neurobiological and behavioral aspects of autism.
Abstract:
Autism is a neurodevelopmental disorder characterized clinically by impairments in social interaction and verbal and non-verbal communication skills as well as restricted interests and repetitive behavior. It has been hypothesized that altered brain environment including an imbalance in neurotrophic support during early development contributes to the pathophysiology of autism. Here we report that sera from children with autism which exhibited abnormal levels of various neurotrophic factors induced cell death and oxidative stress in mouse primary cultured cortical neurons. The effects of sera from autistic children were rescued by pre-treatment with a ciliary neurotrophic factor (CNTF) small peptide mimetic, Peptide 6 (P6), which was previously shown to exert its neuroprotective effect by modulating CNTF/JAK/STAT pathway and LIF signaling and by enhancing brain derived neurotrophic factor (BDNF) expression. Similar neurotoxic effects and neuroinflammation were observed in young Wistar rats injected intracerebroventricularly with autism sera within hours after birth. The autism sera injected rats demonstrated developmental delay and deficits in social communication, interaction, and novelty. Both the neurobiological changes and the behavioral autistic phenotype were ameliorated by P6 treatment. These findings implicate the involvement of neurotrophic imbalance during early brain development in the pathophysiology of autism and a proof of principle of P6 as a potential therapeutic strategy for autism.
