Cited by 86Parkinson's Disease Mechanisms and TreatmentsNeurological disorders and treatmentsNeuroscience and Neuropharmacology Research

Striatal glutamatergic hyperactivity in Parkinson's disease

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Campanelli, F., Natale, G., Marino, G., Ghiglieri, V., Calabresi, P.·2022·Neurobiology of Disease

Abstract

Glutamatergic hyperactivity in the nucleus striatum, the main basal ganglia input, has been involved in the progression of Parkinson's disease (PD) and the onset of L-Dopa-induced dyskinesias (LIDs). Abnormalities in the spiny projection neurons excitability and firing, and in the overactivity of glutamate transmission found in animal models of PD, pointed to the synaptic dysfunctions as a primary target to counteract alterations before overt neurodegeneration, conferring a key role to striatal glutamatergic transmission in the early phases of the disease. The present paper provides an overview of the evidence that glutamatergic overactivity is a critical mechanism underlying different PD-associated striatal alterations in early and advanced symptomatic stages of the disease. These aberrant changes, under L-Dopa therapy, lead to a more complex synaptopathy that involves other neurotransmitter systems and persistent modifications to generate LIDs. The review discusses the main changes in glutamatergic functions found in PD preclinical models and clinical studies and an update of the current pharmacological strategies to modulate the glutamatergic systems at the pre- and postsynaptic levels will be provided.

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  1. Kandel, E.R., et al., 2003. In: Ambrosiana (Ed.), Principi di neuroscienze.

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Authors
Campanelli, F., Natale, G., Marino, G., Ghiglieri, V., & Calabresi, P.
Affiliations
  • Università Cattolica del Sacro Cuore (IT)
  • Agostino Gemelli University Polyclinic (IT)
Corresponding author
  • Ghiglieri, V.
  • Calabresi, P.
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2022-06
Volume
168
Pages
105697
ISSN
0969-9961 (ISSN-L)
OpenAlex
W4220725017
Cited by
86
References
146
Citations by year
2026: 19 · 2025: 32 · 2024: 15 · 2023: 15 · 2022: 5
FWCI
2.42
Type
journal article
Language
en
Open access
Locations
  • Neurobiology of Disease (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • York University
  • Ministero della Salute
  • National Institutes of Health (NS045962)
  • School of Medicine, New York University
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Parkinson's disease, striatum, levodopa-induced dyskinesia, basal ganglia, medium spiny neurons, synaptic dysfunction, glutamatergic neurotransmission, synaptopathy, preclinical animal models, early-stage disease
MeSH terms
Animals, Basal Ganglia, Corpus Striatum, Levodopa, Parkinson Disease, Neostriatum

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