Simultaneous mass spectrometry imaging of multiple neuropeptides in the brain and alterations induced by experimental parkinsonism and L-DOPA therapy

NEUROBIOLOGY OF DISEASE

卷:137

Article

Hulme, Heather^1,2  Fridjonsdottir, Elva¹  Gunnarsdottir, Halla¹  Vallianatou, Theodosia¹  Zhang, Xiaoqun³  Wadensten, Henrik¹  Shariatgorji, Reza^1,2  Nilsson, Anna^1,2  Bezard, Erwan^4,5  Svenningsson, Per³  Andren, Per E.^1,2 

[1] Uppsala Univ, Med Mass Spectrometry Imaging, Dept Pharmaceut Biosci, Uppsala, Sweden

[2] Uppsala Univ, Sci Life Lab, Natl Resource Mass Spectrometry Imaging, Uppsala, Sweden

[3] Karolinska Inst, Sect Neurol, Dept Clin Neurosci, Stockholm, Sweden

[4] Univ Bordeaux, Inst Malad Neurodegenerat, Bordeaux, France

[5] CNRS, Inst Malad Neurodegenerat, Bordeaux, France

关键词: Basal ganglia;    Dynorphin;    Enkephalin;    L-DOPA;    Mass spectrometry imaging;    Neuropeptide;    Parkinson's disease;    Tachykinin;   

DOI  :  10.1016/j.nbd.2020.104738

来源: Elsevier

【 摘 要 】

Neuropeptides are important signalling molecules in the brain and alterations in their expression levels have been linked to neurological disorders such as Parkinson's disease. It is challenging to map neuropeptide changes across and within brain regions because of their low in vivo concentrations and complex post-translational processing. Consequently, the role of neuropeptides in Parkinson's disease is not well understood. Thus, we have developed and evaluated a method to image multiple neuropeptides simultaneously in both rat and primate brain tissue sections by matrix-assisted laser desorption/ionisation mass spectrometry imaging at high lateral resolution. Using a unilateral 6-hydroxydopamine rat model of Parkinson's disease, we imaged changes in enkephalins, dynorphins, tachykinins and neurotensin associated with the dopaminergic denervation and L-DOPA treatment in multiple brain regions. L-DOPA administration significantly affected neuropeptides in the globus pallidus, while neuropeptides in the caudate-putamen were mostly affected by dopamine depletion. Using high lateral resolution imaging, we observed an increase of neurotensin in the dorsal sub-region of the globus pallidus after dopamine depletion. This study highlights the capacity of mass spectrometry imaging to elucidate the dynamics of neuropeptide signalling during Parkinson's disease and its treatment.