Cerebrolysin prevents deficits in social behavior, repetitive conduct, and synaptic inhibition in a rat model of autism
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Autism spectrum disorder (ASD) is a syndrome of diverse neuropsychiatric diseases of growing incidence characterized by repetitive conduct and impaired social behavior and communication for which effective pharmacological treatment is still unavailable. While the mechanisms and etiology of ASD are still unknown, a consensus is emerging about the synaptic nature of the syndrome, suggesting a possible avenue for pharmacological treatment with synaptogenic compounds. The peptidic mixture cerebrolysin (CBL) has been successfully used during the last three decades in the treatment of stroke and neurodegenerative disease. Animal experiments indicate that at least one possible mechanism of action of CBL is through neuroprotection and/or synaptogenesis. In the present study, we tested the effect of CBL treatment (daily injection of 2.5 mL/Kg i.p. during 15 days) on a rat model of ASD. This was based on the offspring (43 male and 51 female pups) of a pregnant female rat injected with valproic acid (VPA, 600 mg/Kg) at the embryonic day 12.5, which previous work has shown to display extensive behavioral, as well as synaptic impairment. Comparison between saline vs. CBL-injected VPA animals shows that CBL treatment improves behavioral as well as synaptic impairments, measured by behavioral performance (social interaction, Y-maze, plus-maze), maximal response of inhibitory γ-amino butyric acid type A receptor (GABAAR)-mediated synaptic currents, as well as their kinetic properties and adrenergic and muscarinic modulation. We speculate that CBL might be a viable and effective candidate for pharmacological treatment or co-treatment of ASD patients. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
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behavior; GABA; patch-clamp; synapses; VPA 4 aminobutyric acid; 4 aminobutyric acid A receptor; cerebrolysin; sodium chloride; amino acid; cerebrolysin; neuroprotective agent; 4 aminobutyric acid release; action potential; animal experiment; animal model; anxiety; Article; autism; cholinergic system; compulsion; controlled study; drug efficacy; electrophysiological procedures; elevated plus maze test; embryo; female; GABAergic transmission; inhibitory postsynaptic potential; male; neuromodulation; nonhuman; priority journal; rat; social behavior; social interaction; synaptic inhibition; synaptic transmission; Y-maze test; animal; animal behavior; autism; brain; disease model; drug effect; social behavior; Sprague Dawley rat; synapse; Amino Acids; Animals; Autistic Disorder; Behavior, Animal; Brain; Disease Models, Animal; Female; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Social Behavior; Synapses
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