Neurodegenerative Diseases

Imarisio A.a· Ferrari E.b· Pilotto A.a· Di Luca M.b· Padovani A.a,b· Gardoni F.b

Author affiliations

aNeurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
bDepartment of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, Milan, Italy

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Article / Publication Details

First-Page Preview

Received: December 28, 2021
Accepted: June 10, 2022
Published online: August 08, 2022

Number of Print Pages: 8
Number of Figures: 3
Number of Tables: 0

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: https://www.karger.com/NDD

Abstract

Introduction: Although neurofilaments are mainly expressed in large caliber myelinated axons, recent evidence supports the existence of a specific synaptic pool, where neurofilament light chain (NfL) has been proposed to stabilize NMDA receptor (NMDAR) at postsynaptic membrane through a direct interaction with the GluN1 subunit. Here, we assessed the expression and synaptic abundance of neurofilaments and their interaction with NMDAR in experimental α-synucleinopathy models. Methods: We used confocal imaging and biochemical approaches to confirm NMDAR-NfL interaction at synapses. Western blotting in purified fractions and co-immunoprecipitation assays were then performed to assess synaptic neurofilament expression and GluN1-NfL interaction in (i) α-synuclein pre-formed fibrils (α-syn PFF)-treated hippocampal neuronal cultures and (ii) mice intrastriatally injected with α-syn-PFF. Results: We identified the existence of a direct protein-protein interaction between NMDAR and NfL endogenously expressed in neurons. Our findings showed increased striatal GluN1-NfL interaction levels at early phases of α-syn PFF-treated mice compared to controls (NfL/GluN1 optical density: α-syn PFF 0.71 ± 0.04; controls 0.48 ± 0.03; t(9) = 4.67; p = 0.001). In agreement with this observation, we found that NfL levels are increased in striatal postsynaptic fractions of α-syn PFF-treated mice (normalized optical density: α-syn PFF 1.86 ± 0.14; controls 1.34 ± 0.13; t(18) = 2.70; p = 0.015). Conclusions: Our results demonstrate alterations of striatal synaptic neurofilament pool in α-synucleinopathy models and open the way to further investigations evaluating a potential role of neurofilament dysregulation in explaining glutamatergic synaptic dysfunction observed in α-synucleinopathies such as Parkinson’s disease.

© 2022 S. Karger AG, Basel

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First-Page Preview

Received: December 28, 2021
Accepted: June 10, 2022
Published online: August 08, 2022

Number of Print Pages: 8
Number of Figures: 3
Number of Tables: 0

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: https://www.karger.com/NDD

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