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Agmatine rescues autistic behaviors in the valproic acid-induced animal model of autism
- Source :
- Neuropharmacology. 113:71-81
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized primarily by two core behavioral symptoms of social communication deficits and restricted/repetitive behaviors. Investigating the etiological process and identifying an appropriate therapeutic target remain as formidable challenges to overcome ASD due to numerous risk factors and complex symptoms associated with the disorder. Among the various mechanisms that contribute to ASD, the maintenance of excitation and inhibition balance emerged as a key factor to regulate proper functioning of neuronal circuitry. Interestingly, our previous study involving the valproic acid animal model of autism (VPA animal model) has demonstrated excitatory-inhibitory imbalance (E/I imbalance) due to enhanced differentiation of glutamatergic neurons and reduced GABAergic neurons. Here, we investigated the potential of agmatine, an endogenous NMDA receptor antagonist, as a novel therapeutic candidate in ameliorating ASD symptoms by modulating E/I imbalance using the VPA animal model. We observed that a single treatment of agmatine rescued the impaired social behaviors as well as hyperactive and repetitive behaviors in the VPA animal model. We also observed that agmatine treatment rescued the overly activated ERK1/2 signaling in the prefrontal cortex and hippocampus of VPA animal models, possibly, by modulating over-excitability due to enhanced excitatory neural circuit. Taken together, our results have provided experimental evidence suggesting a possible therapeutic role of agmatine in ameliorating ASD-like symptoms in the VPA animal model of ASD.
- Subjects :
- Male
0301 basic medicine
Agmatine
Autism Spectrum Disorder
MAP Kinase Signaling System
Primary Cell Culture
Prefrontal Cortex
Hippocampus
Mice, Transgenic
Hyperkinesis
Receptors, N-Methyl-D-Aspartate
Rats, Sprague-Dawley
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Glutamatergic
0302 clinical medicine
Neural Stem Cells
Seizures
medicine
Animals
Social Behavior
Prefrontal cortex
Neurons
Pharmacology
Valproic Acid
medicine.disease
Grooming
Rats
Developmental disorder
Disease Models, Animal
030104 developmental biology
chemistry
Autism spectrum disorder
Autism
Psychology
Neuroscience
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 00283908
- Volume :
- 113
- Database :
- OpenAIRE
- Journal :
- Neuropharmacology
- Accession number :
- edsair.doi.dedup.....4c7fcc9c84d6fe33b7b03693f94e265f