Serotonin (5-HT) neuron-specific inactivation of Cadherin-13 impacts 5-HT system formation and cognitive function

Andrea Forero*, Hsing-Ping Ku, Ana Belen Malpartida, Sina Waeldchen, Judit Alhama-Riba, Christina Kulka, Benjamin Aboagye, William H. J. Norton, Andrew M. J. Young, Yu-Qiang Ding, Robert Blum, Markus Sauer, Olga Rivero, Klaus-Peter Lesch*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Web of Science)

Abstract

Genome-wide screening approaches identified the cell adhesion molecule Cadherin-13 (CDH13) as a risk factor for neurodevelopmental disorders, nevertheless the contribution of CDH13 to the disease mechanism remains obscure. CDH13 is involved in neurite outgrowth and axon guidance during early brain development and we previously provided evidence that constitutive CDH13 deficiency influences the formation of the raphe serotonin (5-HT) system by modifying neuron-radial glia interaction.

Here, we dissect the specific impact of CDH13 on 5-HT system development and function using a 5-HT neuron-specific Cdh13 knockout mouse model (conditional Cdh13 knockout, Cdh13 cKO).

Our results show that exclusive inactivation of CDH13 in 5-HT neurons selectively increases 5-HT neuron density in the embryonic dorsal raphe, with persistence into adulthood, and serotonergic innervation of the developing prefrontal cortex. At the behavioral level, adult Cdh13 cKO mice display delayed acquisition of several learning tasks and a subtle impulsive-like phenotype, with decreased latency in a sociability paradigm alongside with deficits in visuospatial memory. Anxiety-related traits were not observed in Cdh13 cKO mice.

Our findings further support the critical role of CDH13 in the development of dorsal raphe 5-HT circuitries, a mechanism that may underlie specific clinical features observed in neurodevelopmental disorders.

Original languageEnglish
Article number108018
Number of pages14
JournalNeuropharmacology
Volume168
DOIs
Publication statusPublished - 15 May 2020

Keywords

  • Serotonin (5-HT)
  • Raphe nucleus
  • Cadherin-13
  • Cell adhesion molecules
  • Neurodevelopment
  • Learning and memory
  • T-CADHERIN
  • CORTEX
  • DEFICIENCY
  • MODULATION
  • DOPAMINE
  • PATHWAY
  • REGIONS
  • GENES
  • MICE

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