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Beneficial Effect of Erythropoietin on Ameliorating Propionic Acid-Induced Autistic-Like Features in Young Rats
Sara A Hosny1, Alshaymaa M Abdelmenem2, Taha Azouz3
1Histology Department, Faculty of Medicine, Cairo University, Manial, Cairo, Egypt.
Insights
Erythropoietin (EPO) shows promise in mitigating autism-like behaviors in rats induced by propionic acid (PPA). EPO treatment preserved cerebellar structure and reduced oxidative stress, offering potential therapeutic benefits for autism spectrum disorder.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social and communication deficits.
- Propionic acid (PPA) administration in rodents can induce experimental autistic-like behaviors, providing a model for studying ASD.
- Oxidative stress and neuroinflammation are implicated in the pathophysiology of ASD.
Purpose of the Study:
- To investigate the neuroprotective and behavioral effects of erythropoietin (EPO) in a rat model of PPA-induced autistic-like behaviors.
- To assess the impact of EPO on cerebellar structure, oxidative stress markers, and neurotransmitter levels.
Main Methods:
- Rats were divided into control, PPA-induced, and PPA+EPO groups.
- Behavioral changes were assessed, followed by histological and ultrastructural examination of cerebellar tissue.
- Immunohistochemistry for GFAP and calbindin-D28K, and biochemical assays for GSH-Px, MDA, GABA, and serotonin were performed.
Main Results:
- PPA administration induced significant behavioral impairments, reduced cerebellar Purkinje cell counts, and increased oxidative stress (elevated MDA, depleted GSH-Px, GABA, serotonin).
- Histological analysis revealed Purkinje cell degeneration, astrogliosis, and decreased calbindin staining in PPA-treated rats.
- EPO treatment ameliorated behavioral deficits, protected Purkinje cell structure, reduced oxidative stress, and suppressed inflammation.
Conclusions:
- Erythropoietin demonstrates significant protective effects against propionic acid-induced autistic-like features in rats.
- EPO alleviates neuroinflammation and oxidative stress, supporting its potential as a therapeutic agent for ASD-related conditions.
Abstract:
Autism is a neurodevelopmental disorder that impairs communication and social interaction. This study investigated the possible beneficial effects of erythropoietin (EPO) on experimental autistic-like behaviors induced by propionic acid (PPA). Twenty-four rats were distributed into three groups: (i) control; (ii) PPA_Gp: daily injected subcutaneously with PPA for five consecutive days; PPA+EPO-Gp: injected with PPA, then received intraperitoneal injection of EPO once daily for two weeks. Behavioral changes in the rats were assessed. Specimens from the cerebellar hemispheres were subjected to histological and ultrastructure examination, immunohistochemistry for glial fibrillary acidic protein (GFAP) and calbindin-D28K, and biochemical analysis for glutathione peroxidase (GSH-Px), malondialdehyde (MDA), gamma amino-butyric acid (GABA), and serotonin. PPA-Gp showed significant behavioral impairment, with a significant depletion in GSH-px, GABA, and serotonin and a significant increase in MDA. Histological examination revealed reduced Purkinje cell count with ultrastructural degeneration, irregularly arranged nerve fibers in the molecular layer, astrogliosis, and significantly decreased calbindin-immunostaining compared to the control. EPO protected cerebellar structure, increased Purkinje cell count, improved neuronal morphology, reduced PPA-induced autistic-like features, alleviated neuronal oxidative stress, increased intercellular antioxidant levels, and suppressed inflammation. EPO provided significant protection against PPA-induced autistic features in rats, with structural preservation of Purkinje cells.
