Journal article
Knockdown of the Non-canonical Wnt Gene Prickle2 Leads to Cerebellar Purkinje Cell Abnormalities While Cerebellar-Mediated Behaviors Remain Intact
Cerebellum (London, England), Vol.23(5), pp.1741-1753
10/2024
DOI: 10.1007/s12311-023-01648-9
PMCID: PMC11217148
PMID: 38165577
Abstract
Autism spectrum disorders (ASD) involve brain wide abnormalities that contribute to a constellation of symptoms including behavioral inflexibility, cognitive dysfunction, learning impairments, altered social interactions, and perceptive time difficulties. Although a single genetic variation does not cause ASD, genetic variations such as one involving a non-canonical Wnt signaling gene, Prickle2, has been found in individuals with ASD. Previous work looking into phenotypes of Prickle2 knock-out (Prickle2
) and heterozygous mice (Prickle2
) suggest patterns of behavior similar to individuals with ASD including altered social interaction and behavioral inflexibility. Growing evidence implicates the cerebellum in ASD. As Prickle2 is expressed in the cerebellum, this animal model presents a unique opportunity to investigate the cerebellar contribution to autism-like phenotypes. Here, we explore cerebellar structural and physiological abnormalities in animals with Prickle2 knockdown using immunohistochemistry, whole-cell patch clamp electrophysiology, and several cerebellar-associated motor and timing tasks, including interval timing and eyeblink conditioning. Histologically, Prickle2
mice have significantly more empty spaces or gaps between Purkinje cells in the posterior lobules and a decreased propensity for Purkinje cells to fire action potentials. These structural cerebellar abnormalities did not impair cerebellar-associated behaviors as eyeblink conditioning and interval timing remained intact. Therefore, although Prickle
mice show classic phenotypes of ASD, they do not recapitulate the involvement of the adult cerebellum and may not represent the pathophysiological heterogeneity of the disorder.
Details
- Title: Subtitle
- Knockdown of the Non-canonical Wnt Gene Prickle2 Leads to Cerebellar Purkinje Cell Abnormalities While Cerebellar-Mediated Behaviors Remain Intact
- Creators
- Parker W Abbott - University of IowaJason B Hardie - University of IowaKyle P Walsh - University of IowaAaron J Nessler - University of IowaSean J Farley - University of IowaJohn H Freeman - University of IowaJohn A Wemmie - University of IowaLinder Wendt - University of IowaYoung-Cho Kim - University of IowaLevi P Sowers - University of IowaKrystal L Parker - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cerebellum (London, England), Vol.23(5), pp.1741-1753
- DOI
- 10.1007/s12311-023-01648-9
- PMID
- 38165577
- PMCID
- PMC11217148
- NLM abbreviation
- Cerebellum
- ISSN
- 1473-4230
- eISSN
- 1473-4230
- Language
- English
- Electronic publication date
- 01/02/2024
- Date published
- 10/2024
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Psychological and Brain Sciences; Iowa Neuroscience Institute; Biochemistry and Molecular Biology; Neurology (Pediatrics); Neurosurgery
- Record Identifier
- 9984539659602771
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