RESUMO
The genetic traits that underlie vulnerability to neuronal damage across specific brain circuits in Parkinson's disease (PD) remain to be elucidated. In this study, we characterized the brain topological intersection between propagating connectivity networks in controls and PD participants and gene expression patterns across the human cortex - such as the SNCA gene. We observed that brain connectivity originated from PD-related pathology epicenters in the brainstem recapitulated the anatomical distribution of alpha-synuclein histopathology in postmortem data. We also discovered that the gene set most related to cortical propagation patterns of PD-related pathology was primarily involved in microtubule cellular components. Thus, this study sheds light on new avenues for enhancing detection of PD neuronal vulnerability via an evaluation of in vivo connectivity trajectories across the human brain and successful integration of neuroimaging-genetic strategies.
Assuntos
Doença de Parkinson , Encéfalo/patologia , Humanos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/genética , Doença de Parkinson/patologiaRESUMO
The diagnosis of Parkinson's disease (PD) is still based on the recognition of the cardinal motor features. However, it is now recognized that non-motor manifestations (NMM) may actually precede the emergence of motor manifestations. NMM are very frequently present in the overall population of PD patients and are a major determinant of their quality of life. In this article we discuss the origin of sensory manifestations in PD, particularly focus on pain mechanisms, which is the most frequent and better studied NMM. Analysis of experimental and clinical data reveals that the basal ganglia (BG) indeed have an anatomo-functional organization which sustains sensory functions. In addition, the dopaminergic system is also engaged in the modulation and integration of sensory information and the response to pain. In patients with PD, pain is often related with motor fluctuations and dyskinesias induced by dopaminergic treatments, which suggest some common mechanisms with the origin of motor complications in PD. Clinically, sensory manifestations are often disturbing and poorly treated and may occasionally become a major cause of disability for PD patients. Thus, more clinical and basic studies are warranted to clarify pain mechanisms in PD, with the aim of achieving better treatments.