Cerebrolysin prevents deficits in social behavior, repetitive conduct, and synaptic inhibition in a rat model of autism.

Roberto Cuevas-Olguin, Swagata Roychowdhury, Anwesha Banerjee, Francisco Garcia-Oscos, Eric Esquivel-Rendon, María Elena Bringas, Michael P Kilgard, Gonzalo Flores, Marco Atzori
Author Information
  1. Roberto Cuevas-Olguin: Facultad de Ciencias, Programa de Biología, Universidad Autónoma de San Luis Potosí, San Luis Potosí, SLP, 78290, México.
  2. Swagata Roychowdhury: National Institute of Children and Human Development, NIH, Bethesda, MD, 20892, USA.
  3. Anwesha Banerjee: School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, 75080, USA.
  4. Francisco Garcia-Oscos: Department of Neuroscience, University of Texas Southwestern, Dallas, TX, 75390, USA.
  5. Eric Esquivel-Rendon: Facultad de Ciencias, Programa de Biología, Universidad Autónoma de San Luis Potosí, San Luis Potosí, SLP, 78290, México.
  6. María Elena Bringas: Benemerita Universidad Autónoma de Puebla, Instituto de Fisiología, Puebla Pue., 72000, México.
  7. Michael P Kilgard: School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, 75080, USA.
  8. Gonzalo Flores: Benemerita Universidad Autónoma de Puebla, Instituto de Fisiología, Puebla Pue., 72000, México.
  9. Marco Atzori: Facultad de Ciencias, Programa de Biología, Universidad Autónoma de San Luis Potosí, San Luis Potosí, SLP, 78290, México. ORCID

Abstract

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 (GABA R)-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.

Keywords

MeSH Term

Amino Acids
Animals
Autistic Disorder
Behavior, Animal
Brain
Disease Models, Animal
Female
Male
Neuroprotective Agents
Rats
Rats, Sprague-Dawley
Social Behavior
Synapses

Chemicals

Amino Acids
Neuroprotective Agents
cerebrolysin

Word Cloud

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