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Mood disorders in Huntington's disease: from behavior to cellular and molecular mechanisms

Patrick Pla1, Sophie Orvoen2, Frédéric Saudou3

  • 1Institut Curie Orsay, France ; CNRS UMR3306 Orsay, France ; INSERM U1005 Orsay, France ; Faculté des Sciences, Université Paris-Sud Orsay, France.

Frontiers in Behavioral Neuroscience
|May 6, 2014
PubMed

Insights

Huntington's disease (HD) involves mood disturbances like depression and anxiety, often preceding motor symptoms. Pathogenic huntingtin (HTT) dysfunction disrupts cellular pathways crucial for mood regulation and neurogenesis, contributing to these behavioral changes.

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Huntington's disease (HD) is a neurodegenerative disorder primarily affecting motor control.
  • Mood disturbances, including depression and anxiety, are highly prevalent in HD patients, often appearing before motor symptoms.
  • Rodent models of HD exhibit anxiety and depressive behaviors similar to human patients.

Purpose of the Study:

  • To review the cellular and molecular mechanisms underlying behavioral disorders in Huntington's disease.
  • To explore the role of huntingtin (HTT) dysfunction in mood disturbances associated with HD.
  • To understand how pathogenic HTT affects neuronal pathways and neurogenesis.

Main Methods:

  • Literature review of studies on Huntington's disease cellular and molecular mechanisms.
  • Analysis of research on huntingtin protein (HTT) function and dysfunction.
  • Examination of findings related to BDNF/TrkB signaling, serotonergic pathways, and adult hippocampal neurogenesis in HD models.

Main Results:

  • Dysfunctional huntingtin (HTT) impacts cellular pathways involved in mood regulation and antidepressant response, such as BDNF/TrkB and serotonergic signaling.
  • Huntingtin (HTT) influences adult hippocampal neurogenesis, a process linked to anxiety control and antidepressant effects.
  • The pathogenic polyglutamine expansion in HTT may cause mood disorders through toxic gain of function or by disrupting normal HTT function.

Conclusions:

  • Wild-type huntingtin (HTT) plays a critical role in neuronal development and physiology.
  • Perturbation of normal HTT function, in addition to toxic gain of function, contributes to mood disorders in Huntington's disease.
  • Understanding these mechanisms offers insights into potential therapeutic strategies for HD-associated behavioral symptoms.

Keywords:
BDNFHPA axisHuntingtinHuntington's diseaseanxietydepressionneurogenesisserotonin

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