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

Elva Fridjonsdottir¹  Per E. Andrén¹  Erwan Bezard¹  Reza Shariatgorji²  Anna Nilsson²  Xiaoqun Zhang²  Per Svenningsson²  Heather Hulme²  Halla Gunnarsdottir²  Theodosia Vallianatou²  Henrik Wadensten³ 

[1] Science for Life Laboratory, National Resource for Mass Spectrometry Imaging, Uppsala University, Uppsala, Sweden;

[2] Medical Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden;

[3] Section of Neurology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden;

关键词: Basal ganglia;    Dynorphin;    Enkephalin;    L-DOPA;    Mass spectrometry imaging;    Neuropeptide;   

DOI  :  

来源: DOAJ

【 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.

【 授权许可】

Unknown