Effects of Infliximab in a Propionic Acid-Induced Experimental Autism Rat Model.

Area of Science:

• Neuroscience
• Immunology
• Developmental Biology

Background:

• Autism spectrum disorder (ASD) is linked to neuroinflammation and altered neurotrophic factors.
• Tumor necrosis factor-alpha (TNF-α) is implicated in ASD, but its blockade effects on neurodevelopment are unclear.

Purpose of the Study:

• To investigate the impact of infliximab (IFX), an anti-TNF-α antibody, on behavioral outcomes, neuroinflammation, and brain-derived neurotrophic factor (BDNF) signaling in an experimental ASD rat model.
• To assess the effects of TNF-α blockade on cytokine-neurotrophin interactions during neurodevelopment.

Main Methods:

• Propionic acid (PPA) induced an ASD model in rats.
• Behavioral tests (Morris Water Maze, social interaction) assessed cognitive and social deficits.
• Cytokine (TNF-α, IL-1β, IL-6) and BDNF levels were measured; glial activation was assessed via immunohistochemistry.

Main Results:

• PPA-induced ASD rats showed learning, memory, and social impairments with elevated cytokines and BDNF.
• IFX treatment reduced TNF-α but failed to improve behavior.
• IFX was associated with persistent IL-1β/IL-6 elevation, sustained glial activation, and altered BDNF levels.

Conclusions:

• Single-agent TNF-α blockade does not normalize the neuroimmune-neurotrophic axis in experimental ASD.
• Non-selective TNF-α blockade during development may not yield behavioral benefits and can alter BDNF signaling.
• Targeting cytokine-BDNF interactions is crucial for developing effective immunomodulatory strategies for neurodevelopmental disorders.