Animal models of dystonia

Lessons from a mutant rat

Research output: Contribution to journalReview article

37 Citations (Scopus)

Abstract

Dystonia is a motor sign characterized by involuntary muscle contractions which produce abnormal postures. Genetic factors contribute significantly to primary dystonia. In comparison, secondary dystonia can be caused by a wide variety of metabolic, structural, infectious, toxic and inflammatory insults to the nervous system. Although classically ascribed to dysfunction of the basal ganglia, studies of diverse animal models have pointed out that dystonia is a network disorder with important contributions from abnormal olivocerebellar signaling. In particular, work with the dystonic (dt) rat has engendered dramatic paradigm shifts in dystonia research. The dt rat manifests generalized dystonia caused by deficiency of the neuronally restricted protein caytaxin. Electrophysiological and biochemical studies have shown that defects at the climbing fiber-Purkinje cell synapse in the dt rat lead to abnormal bursting firing patterns in the cerebellar nuclei, which increases linearly with postnatal age. In a general sense, the dt rat has shown the scientific and clinical communities that dystonia can arise from dysfunctional cerebellar cortex. Furthermore, work with the dt rat has provided evidence that dystonia (1) is a neurodevelopmental network disorder and (2) can be driven by abnormal cerebellar output. In large part, work with other animal models has expanded upon studies in the dt rat and shown that primary dystonia is a multi-nodal network disorder associated with defective sensorimotor integration. In addition, experiments in genetically engineered models have been used to examine the underlying cellular pathologies that drive primary dystonia. This article is part of a Special Issue entitled "Advances in dystonia".

Original languageEnglish (US)
Pages (from-to)152-161
Number of pages10
JournalNeurobiology of Disease
Volume42
Issue number2
DOIs
StatePublished - May 1 2011

Fingerprint

Dystonia
Animal Models
Dystonic Disorders
Cerebellar Nuclei
Cerebellar Cortex
Poisons
Purkinje Cells
Muscle Contraction
Basal Ganglia
Posture
Synapses
Nervous System
Smooth Muscle
Pathology
Research

All Science Journal Classification (ASJC) codes

  • Neurology

Cite this

Animal models of dystonia : Lessons from a mutant rat. / Ledoux, Mark.

In: Neurobiology of Disease, Vol. 42, No. 2, 01.05.2011, p. 152-161.

Research output: Contribution to journalReview article

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