Extracellular matrix protein anosmin-1 overexpression alters dopaminergic phenotype in the CNS and the PNS with no pathogenic consequences in a MPTP model of Parkinson’s disease

Abstract

The development and survival of dopaminergic neurons are influenced by the fibroblast growth factor (FGF) pathway. Anosmin-1 (A1) is an extracellular matrix protein that acts as a major regulator of this signaling pathway, controlling FGF diffusion, and receptor interaction and shuttling. In particular, previous work showed that A1 overexpression results in more dopaminergic neurons in the olfactory bulb. Prompted by those intriguing results, in this study, we investigated the effects of A1 overexpression on different populations of catecholaminergic neurons in the central (CNS) and the peripheral nervous systems (PNS). We found that A1 overexpression increases the number of dopaminergic substantia nigra pars compacta (SNpc) neurons and alters the striosome/matrix organization of the striatum. Interestingly, these numerical and morphological changes in the nigrostriatal pathway of A1-mice did not confer an altered susceptibility to experimental MPTP-parkinsonism with respect to wild-type controls. Moreover, the study of the effects of A1 overexpression was extended to different dopaminergic tissues associated with the PNS, detecting a significant reduction in the number of dopaminergic chemosensitive carotid body glomus cells in A1-mice. Overall, our work shows that A1 regulates the development and survival of dopaminergic neurons in different nuclei of the mammalian nervous system.

A Systematic Review of Extracellular Matrix-Related Alterations in Parkinson’s Disease

“…Articles were included if they (1) described published, peer-reviewed research studies of transcriptomics, proteomics, or genomics in PD, (2) were conducted using tissues or cells derived from humans with PD, (3) employed gene set enrichment analysis (GSEA), and (4) identified one or more ECM-related pathway among the top-10 enriched gene sets. Reviews, preprints, and studies that evaluated ECM in animal models of PD were excluded, although very few studies have reported changes in the ECM in animal models of PD [ 19 , 20 , 21 ], with the major focus on matrix metalloproteinases (MMPs), which regulate the ECM [ 22 , 23 , 24 ]; for review, see [ 25 ]. Studies conducted in multiple disease populations were also excluded unless results for Parkinson’s disease patients were reported separately.…”