Skip to content
Project Directory
  • Français
Donate Now
  • Français
  • About
    • What We Do
    • Leadership
    • Team
    • Publications
    • Careers
  • Diseases/Disorders
    • One Brain
    • ALS
    • Alzheimer’s
    • Autism
    • Brain Cancer
    • Brain Injury
    • Epilepsy
    • Mental Illness
    • Multiple Sclerosis
    • Parkinson’s
    • Stroke
    • Other
  • Research
    • Programs
    • Funding Opportunities
    • Program Partners
    • Announcements
  • Impact
  • Ways To Give
    • Giving to Research
    • How You Can Help
    • Events

Funded Grants

Back to results

Impaired translational regulation of brain development in autism spectrum disorders

Project Overview

Autism spectrum disorders (ASDs) are a group of complex neurodevelopmental disorders with distinguished early emerging behavioral disruptions (speech impairments, social communication, repetitive behaviors) and a rising rate of diagnosis to an estimated 1 in 68 children. Synaptogenesis occurs in the vertebrate central nervous system from early embryonic life to adulthood. Proper assembly of neural circuits during synaptogenesis depends on the balance between excitatory and inhibitory (E/I) inputs. Disruption of this balance can lead to neurodevelopmental disorders such as autism, epilepsy, Rett syndrome or Fragile X syndrome. Gamma-aminobutyric acid (GABA) is a main inhibitory neurotransmitter in the brain, but during early development, GABAergic currents are mainly excitatory. The shift from excitatory to inhibitory actions of GABA occurs between the first two postnatal weeks in rodents due to the reduction of intracellular chloride concentration which is mediated by a decrease in the expression of the main chloride importer, NKCC1, and an increase in the main chloride exporter, KCC2. Protein synthesis (mRNA translation) is an essential process in all organisms. Eukaryotic translation initiation factor 4E (eIF4E) is the least abundant translation-initiation factor, and its activity is rate-limiting and tightly regulated. 4E-BP2 is the major eIF4E-binding protein which acts as a translational suppressor. It has an important role in long-lasting synaptic plasticity, learning, and memory. Dysregulation of chloride homeostasis and a delay in the shift of GABAergic transmission during synaptogenesis in BP2KO mice could be the cause of the ASD-like phenotype observed in these mice. Therefore, normalization of the increased NKCC1/KCC2 ratio using bumetanide, in order to reverse ASD-like phenotypes, could provide an important insight into the developmental mechanisms of translational control in ASD and might lead to a new pharmaco-therapeutical direction for the prevention of behavioral impairments in ASD.

Principal Investigator

Jelena Popic , McGill University

Partners and Donors

Azrieli Foundation

McGill University

Project Ongoing

Impaired translational regulation of brain development in autism spectrum disorders

  • Program Type

    Capacity building grants

  • Area of research

    Neurodevelopment

  • Disease Area

    Autism

  • Competition

    Brain Canada - Kids Brain Health Network Training Awards

  • Province

    Québec

  • Start Date

    2016

  • Total Grant Amount

    $110,000

  • Health Canada Contribution

    $55,000

Contact Us

1200 McGill College Avenue
Suite 1600, Montreal, Quebec
H3B 4G7

+1 (514) 989-2989 info@braincanada.ca

Playing with Marbles Podcast

Join us and take a journey to the real last great frontier – the brain.

Listen

Subscribe to Brain News

Receive our monthly electronic newsletter with updates on funded projects, upcoming events and breakthroughs in brain research.

Sign Up

Territorial acknowledgement

The offices of Brain Canada Foundation are located on the traditional, ancestral territory of the Kanien'kehá:ka Peoples, a place which has long served as a site of meeting and exchange amongst nations. We honour and pay respect to elders past, present and emerging, and dedicate ourselves to moving forward in the spirit of partnership, collaboration, and reconciliation. In our work, we focus our efforts on the Truth and Reconciliation Commission’s Calls to Action, particularly those that pertain to improving health for Indigenous Peoples and that focus on advancing our own learning on Indigenous issues.

© 2023 Brain Canada Foundation

Registration number: 89105 2094 RR0001

  • Terms and Conditions
  • Privacy Policy

Design by Field Trip & Co