Impaired intracortical transmission in G2019S leucine rich‐repeat kinase Parkinson patients
- 10 February 2017
- journal article
- research article
- Published by Wiley in Movement Disorders
- Vol. 32 (5), 750-756
- https://doi.org/10.1002/mds.26931
Abstract
Objectives: A mutation in leucine-rich repeat kinase 2 is the most common cause of hereditary Parkinson's disease (PD), yet the neural mechanisms and the circuitry potentially involved are poorly understood. Methods: We used different transcranial magnetic stimulation protocols to explore in the primary motor cortex the activity of intracortical circuits and cortical plasticity (long-term potentiation) in patients with the G2019S leucine-rich repeat kinase 2 gene mutation when compared with idiopathic PD patients and age-matched healthy subjects. Paired pulse transcranial magnetic stimulation was used to investigate short intracortical inhibition and facilitation and short afferent inhibition. Intermittent theta burst stimulation, a form of repetitive transcranial magnetic stimulation, was used to test long-term potentiation-like cortical plasticity. Leucine-rich repeat kinase 2 and idiopathic PD were tested both in ON and in OFF l-dopa therapy. Results: When compared with idiopathic PD and healthy subjects, leucine-rich repeat kinase 2 PD patients showed a remarkable reduction of short intracortical inhibition in both ON and in OFF l-dopa therapy. This reduction was paralleled by an increase of intracortical facilitation in OFF l-dopa therapy. Leucine-rich repeat kinase 2 PD showed abnormal long-term potentiation-like cortical plasticity in ON l-dopa therapy. Discussion: The motor cortex in leucine-rich repeat kinase 2 mutated PD patients is strongly disinhibited and hyperexcitable. These abnormalities could be a result of an impairment of inhibitory (gamma-Aminobutyric acid) transmission eventually related to altered neurotransmitter release. © 2017 International Parkinson and Movement Disorder SocietyKeywords
This publication has 30 references indexed in Scilit:
- Transcranial magnetic stimulation follow‐up study in early Parkinson's disease: A decline in compensation with disease progression?Movement Disorders, 2015
- LRRK2 Affects Vesicle Trafficking, Neurotransmitter Extracellular Level and Membrane Receptor LocalizationPLOS ONE, 2013
- Dopaminergic Neuronal Loss, Reduced Neurite Complexity and Autophagic Abnormalities in Transgenic Mice Expressing G2019S Mutant LRRK2PLOS ONE, 2011
- LRRK2 regulates synaptic vesicle endocytosisExperimental Cell Research, 2008
- The Familial Parkinsonism Gene LRRK2 Regulates Neurite Process MorphologyNeuron, 2006
- Genetics of Parkinson disease: paradigm shifts and future prospectsNature Reviews Genetics, 2006
- Mutations in LRRK2 Cause Autosomal-Dominant Parkinsonism with Pleomorphic PathologyNeuron, 2004
- Cloning of the Gene Containing Mutations that Cause PARK8-Linked Parkinson's DiseaseNeuron, 2004
- Intracortical inhibition and facilitation are impaired in patients with early Parkinson's disease: a paired TMS studyEuropean Journal of Neurology, 2003
- Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.Journal of Neurology, Neurosurgery & Psychiatry, 1992