Excitotoxic neurodegeneration is associated with a focal decrease in metabotropic glutamate receptor type 5 availability: an in vivo PET imaging study

Autor: Melissa Crabbé, Koen Van Laere, Nina Dirkx, Cindy Casteels
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
ALPHA-SYNUCLEIN
animal diseases
Excitotoxicity
lcsh:Medicine
PROTEIN
Striatum
medicine.disease_cause
ACTIVATION
chemistry.chemical_compound
0302 clinical medicine
PARKINSONS-DISEASE
RAT MODEL
Image Processing
Computer-Assisted
VITRO
lcsh:Science
Multidisciplinary
Behavior
Animal
Metabotropic glutamate receptor 5
Glutamate receptor
Neurodegenerative Diseases
Immunohistochemistry
Multidisciplinary Sciences
Experimental models of disease
Globus pallidus
QUINOLINIC ACID
Science & Technology - Other Topics
Cell Survival
Receptor
Metabotropic Glutamate 5
MGLUR5
Glutamic Acid
Nucleus accumbens
Article
03 medical and health sciences
mental disorders
medicine
Animals
Science & Technology
business.industry
lcsh:R
Excitatory Postsynaptic Potentials
Corpus Striatum
Rats
Disease Models
Animal
030104 developmental biology
chemistry
NMDA
nervous system
Metabotropic glutamate receptor
NEUROTOXICITY
Positron-Emission Tomography
Diseases of the nervous system
lcsh:Q
business
Neuroscience
030217 neurology & neurosurgery
Biomarkers
Quinolinic acid
Zdroj: Scientific Reports
Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
ISSN: 2045-2322
Popis: Metabotropic glutamate receptors (mGluRs) have been proposed as promising therapeutic targets to correct the dysregulated glutamate signaling, associated with neurodegenerative pathologies. Of all mGluR subtypes, especially mGluR5 acts as a modulator of glutamate-induced excitotoxicity. To study the behavior of mGluR5 following localized excitotoxicity, we utilised a pharmacological model that portrays exacerbated neuronal glutamate release, mediated by the endogenous excitotoxin quinolinic acid (QA). Using longitudinal positron emission tomography (PET) with [18F]FPEB, we investigated cerebral changes in mGluR5 following striatal QA-lesioning. Behavioral tests were executed to monitor motor and cognitive performance. Decreased mGluR5 binding potential (BPND) was found in the affected striatum and globus pallidus of QA-lesioned rats at week 3, and further decreased at week 7, as compared to sham-injected controls. mGluR5 availability in the ipsilateral nucleus accumbens was significantly decreased at 7 weeks post-injection. QA rats performed significantly worse on motor coordination and balance compared to control rats. Correlation analysis indicated a positive correlation between striatal mGluR5 BPND and rotarod performance whereas print width of the unaffected forepaws showed a positive relation with mGluR5 BPND in the contralateral motor cortex. Together, our results suggest decreased mGluR5 availability to be related to excitotoxin-induced neurodegeneration and symptomatology although late stage effects do indicate possible cortical mGluR5-mediated effects on motor behavior.
Databáze: OpenAIRE
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