Aperçu: G.M.
Alors
que les mécanismes et l'étiologie des TSA sont encore inconnus, un
consensus surgit sur la nature synaptique du syndrome, suggérant une
voie possible pour le traitement pharmacologique avec des composés
synaptogéniques. Le
mélange peptidique de la célylysine (CBL) a été utilisé avec succès au
cours des trois dernières décennies dans le traitement des accidents
vasculaires cérébraux et des maladies neurodégénératives. Les
expériences sur les animaux indiquent qu'au moins un mécanisme d'action
possible de CBL est réalisé par neuroprotection et / ou synaptogenèse.
Dans
la présente étude, les chercheurs ont testé l'effet du traitement CBL
(injection quotidienne de 2,5 mL / Kg i.p. pendant 15 jours) sur un
modèle murin de TSA.
La
comparaison entre l'injection d'une solution saline et de CBL montre que
le traitement CBL améliore les déficiences comportementales et
synaptiques, mesurées par la performance comportementale (interaction
sociale, labyrinthe Y, plus-labyrinthe), réponse maximale de l'inhibiteur de type A de l'acide
γ-amino butyrique, les
courants synaptiques médiés par le récepteur (GABAA R), ainsi que leurs
propriétés cinétiques et leur modulation adrénergique et muscarinique.
J Neurosci Res. 2017 Jun 13. doi: 10.1002/jnr.24072.
Cerebrolysin prevents deficits in social behavior, repetitive conduct, and synaptic inhibition in a rat model of autism
Cuevas-Olguin R1, Roychowdhury S2, Banerjee A3,4, Garcia-Oscos F5, Esquivel-Rendon E1, Bringas ME6, Kilgard MP3, Flores G6, Atzori M1,3.
Author information
- 1
- Facultad de Ciencias, Programa de Biología, Universidad Autónoma de San Luis Potosí, San Luis Potosí, SLP, 78290, México.
- 2
- National Institute of Children and Human Development, NIH, Bethesda, MD, 20892, USA.
- 3
- School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, 75080, USA.
- 4
- Emory School of Medicine, Department of Cell Biology, Emory University, 615 Michael St. WBRB #415, Atlanta, GA 30322, USA.
- 5
- Department of Neuroscience, University of Texas Southwestern, Dallas, TX, 75390, USA.
- 6
- Benemerita Universidad Autónoma de Puebla, Instituto de Fisiología, Puebla Pue., 72000, México.
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
(GABAA 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.
© 2017 Wiley Periodicals, Inc.
- PMID:28609577
- DOI:10.1002/jnr.24072
