Sensitive Periods for Cerebellar-Mediated Autistic-like Behaviors

Peter T. Tsai, Stephanie Rudolph, Chong Guo, Jacob Ellegood, Jennifer M. Gibson, Samantha M. Schaeffer, Jazmin Mogavero, Jason P. Lerch, Wade Regehr, Mustafa Sahin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Despite a prevalence exceeding 1%, mechanisms underlying autism spectrum disorders (ASDs) are poorly understood, and targeted therapies and guiding parameters are urgently needed. We recently demonstrated that cerebellar dysfunction is sufficient to generate autistic-like behaviors in a mouse model of tuberous sclerosis complex (TSC). Here, using the mechanistic target of rapamycin (mTOR)-specific inhibitor rapamycin, we define distinct sensitive periods for treatment of autistic-like behaviors with sensitive periods extending into adulthood for social behaviors. We identify cellular and electrophysiological parameters that may contribute to behavioral rescue, with rescue of Purkinje cell survival and excitability corresponding to social behavioral rescue. In addition, using anatomic and diffusion-based MRI, we identify structural changes in cerebellar domains implicated in ASD that correlate with sensitive periods of specific autism-like behaviors. These findings thus not only define treatment parameters into adulthood, but also support a mechanistic basis for the targeted rescue of autism-related behaviors. A mechanistic understanding of and establishment of time windows for effective therapy (sensitive periods) for autism-related behaviors remain unknown. Tsai et al. delineate specific time windows for treatment of specific autism-relevant behaviors and evaluate underlying cellular, electrophysiological, and anatomic mechanisms for these sensitive periods.

Original languageEnglish (US)
Pages (from-to)357-367.e4
JournalCell Reports
Volume25
Issue number2
DOIs
StatePublished - Oct 9 2018

Fingerprint

Sirolimus
Autistic Disorder
Magnetic resonance imaging
Cells
Cerebellar Diseases
Tuberous Sclerosis
Diffusion Magnetic Resonance Imaging
Social Behavior
Purkinje Cells
Cell Survival
Therapeutics
Autism Spectrum Disorder

Keywords

  • autism
  • cerebellum
  • Purkinje cell
  • sensitive periods
  • treatment
  • tuberous sclerosis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Tsai, P. T., Rudolph, S., Guo, C., Ellegood, J., Gibson, J. M., Schaeffer, S. M., ... Sahin, M. (2018). Sensitive Periods for Cerebellar-Mediated Autistic-like Behaviors. Cell Reports, 25(2), 357-367.e4. https://doi.org/10.1016/j.celrep.2018.09.039

Sensitive Periods for Cerebellar-Mediated Autistic-like Behaviors. / Tsai, Peter T.; Rudolph, Stephanie; Guo, Chong; Ellegood, Jacob; Gibson, Jennifer M.; Schaeffer, Samantha M.; Mogavero, Jazmin; Lerch, Jason P.; Regehr, Wade; Sahin, Mustafa.

In: Cell Reports, Vol. 25, No. 2, 09.10.2018, p. 357-367.e4.

Research output: Contribution to journalArticle

Tsai, PT, Rudolph, S, Guo, C, Ellegood, J, Gibson, JM, Schaeffer, SM, Mogavero, J, Lerch, JP, Regehr, W & Sahin, M 2018, 'Sensitive Periods for Cerebellar-Mediated Autistic-like Behaviors', Cell Reports, vol. 25, no. 2, pp. 357-367.e4. https://doi.org/10.1016/j.celrep.2018.09.039
Tsai PT, Rudolph S, Guo C, Ellegood J, Gibson JM, Schaeffer SM et al. Sensitive Periods for Cerebellar-Mediated Autistic-like Behaviors. Cell Reports. 2018 Oct 9;25(2):357-367.e4. https://doi.org/10.1016/j.celrep.2018.09.039
Tsai, Peter T. ; Rudolph, Stephanie ; Guo, Chong ; Ellegood, Jacob ; Gibson, Jennifer M. ; Schaeffer, Samantha M. ; Mogavero, Jazmin ; Lerch, Jason P. ; Regehr, Wade ; Sahin, Mustafa. / Sensitive Periods for Cerebellar-Mediated Autistic-like Behaviors. In: Cell Reports. 2018 ; Vol. 25, No. 2. pp. 357-367.e4.
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