Developmental molecular and functional cerebellar alterations induced by PCP4/PEP19 overexpression: implications for Down syndrome.

Abstract : PCP4/PEP19 is a modulator of Ca(2+)-CaM signaling. In the brain, it is expressed in a very specific pattern in postmitotic neurons. In particular, Pcp4 is highly expressed in the Purkinje cell, the sole output neuron of the cerebellum. PCP4, located on human chromosome 21, is present in three copies in individuals with Down syndrome (DS). In a previous study using a transgenic mouse model (TgPCP4) to evaluate the consequences of 3 copies of this gene, we found that PCP4 overexpression induces precocious neuronal differentiation during mouse embryogenesis. Here, we report combined analyses of the cerebellum at postnatal stages (P14 and adult) in which we identified age-related molecular, electrophysiological, and behavioral alterations in the TgPCP4 mouse. While Pcp4 overexpression at P14 induces an earlier neuronal maturation, at adult stage it induces increase in cerebellar CaMK2alpha and in cerebellar LTD, as well as learning impairments. We therefore propose that PCP4 contributes significantly to the development of Down syndrome phenotypes through molecular and functional changes.
Document type :
Journal articles
Complete list of metadatas

https://hal.archives-ouvertes.fr/hal-01179506
Contributor : Isabelle Frapart <>
Submitted on : Wednesday, July 22, 2015 - 4:17:03 PM
Last modification on : Friday, June 28, 2019 - 9:38:04 AM

Identifiers

  • HAL Id : hal-01179506, version 1
  • PUBMED : 24291518

Citation

François Mouton-Liger, Ignasi Sahún, Thibault Collin, Patricia Lopes Pereira, Debora Masini, et al.. Developmental molecular and functional cerebellar alterations induced by PCP4/PEP19 overexpression: implications for Down syndrome.. Neurobiology of Disease, Elsevier, 2014, 63, pp.92-106. ⟨hal-01179506⟩

Share

Metrics

Record views

168