Background: The translocator protein (TSPO; 18 kDa), the new name of the peripheral-type benzodiazepine receptor, is localised in mitochondria of glial cells and expressed in very low concentrations in normal brain. Their expression rises after microglial activation following brain injury. Accordingly, TSPO are potential targets to evaluate neuroinflammatory changes in a variety of CNS disorders.
Purpose: To date, only a few effective tools are available to explore TSPO by SPECT. We characterised here 6-chloro-2-(4'iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide or CLINDE in a rat model with different stages of excitotoxic lesion.
Methods: Excitotoxicity was induced in male Wistar rats by unilateral intrastriatal injection of different amounts of quinolinic acid (75, 150 or 300 nmol). Six days later, two groups of rats (n = 5-6/group) were i.v. injected with [(125)I]-CLINDE (0.4 MBq); one group being pre-injected with PK11195 (5 mg/kg). Brains were removed 30 min after tracer injection and the radioactivity of cerebral areas measured. Complementary ex vivo autoradiography, in vitro autoradiography ([(3)H]-PK11195) and immunohistochemical studies (OX-42) were performed on brain sections.
Results: In the control group, [(125)I]-CLINDE binding was significantly higher (p < 0.001) in lesioned than that in intact side. This binding disappeared in rats pre-treated with PK11195 (p < 0.001), showing specific binding of CLINDE to TSPO. Ex vivo and in vitro autoradiographic studies and immunohistochemistry were consistent with this, revealing a spatial correspondence between radioactivity signal and activated microglia. Regression analysis yielded a positive relation between the ligand binding and the degree of neuroinflammation.
Conclusion: These results demonstrate that CLINDE is suitable for TSPO in vivo SPECT imaging to explore their involvement in neurodegenerative disorders associated with microglial activation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00259-008-0834-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Blood-brain barrier disruption and microglial activation during hypoxia and post-hypoxic recovery in aged mice.
Brain Commun
December 2024
San Diego Biomedical Research Institute, San Diego, CA 92121, USA.
Hypoxia triggers blood-brain barrier disruption and a strong microglial activation response around leaky cerebral blood vessels. These events are greatly amplified in aged mice which is translationally relevant because aged patients are far more likely to suffer hypoxic events from heart or lung disease, and because of the pathogenic role of blood-brain barrier breakdown in vascular dementia. Importantly, it is currently unclear if disrupted cerebral blood vessels spontaneously repair and if they do, whether surrounding microglia deactivates.
View Article and Find Full Text PDFThioredoxin-interacting protein (TXNIP) inhibition promotes retinal ganglion cell survival and facilitates M1-like microglial transformation via the PI3K/Akt pathway in glaucoma.
Mol Med
December 2024
Department of Ophthalmology, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, 197 Ruijin er Road, Shanghai, 200025, China.
Background: Glaucoma is a group of heterogeneous neurodegenerative diseases with abnormal energy metabolism and imbalanced neuroinflammation in the retina. Thioredoxin-interacting protein (TXNIP) is involved in glucose and lipid metabolism, and associated with oxidative stress and inflammation, however, not known whether to be involved in glaucoma neuropathy and its underlying mechanisms.
Methods: To establish the chronic ocular hypertension (COH) mice model.
Icariin maintaining TMEM119-positive microglial population improves hippocampus-associated memory in senescent mice in relation to R-3-hydroxybutyric acid metabolism.
J Ethnopharmacol
December 2024
Central Laboratory, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address:
Ethnopharmacological Relevance: Epimedium Tourn. ex L. is a traditional Chinese medicine used for thousands of years in China to treat forgetfulness.
View Article and Find Full Text PDFPentraxin 3 promotes microglial M2 polarization and excitatory synapse formation in the hippocampus in depression.
Int Immunopharmacol
December 2024
Department of Radiology, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212001, China. Electronic address:
Depression is a prevalent mental illness that significantly impairs individuals' overall quality of life and physical well-being. However, the pathological mechanisms of depression remain unclear, and effective treatment strategies are urgently needed. Pentraxin 3 (PTX3), a long pentraxin protein, plays a significant role in various pathological conditions, including infections, immune responses, and tissue repair.
View Article and Find Full Text PDFCLEC7A Knockdown Alleviates Ischemic Stroke by Inhibiting Pyroptosis and Microglia Activation.
J Integr Neurosci
December 2024
Department of Neurology, Hainan West Central Hospital, 571799 Danzhou, Hainan, China.
Background: Ischemic stroke (IS) is the leading cause of mortality worldwide. Herein, we aimed to identify novel biomarkers and explore the role of C-type lectin domain family 7 member A () in IS.
Methods: Differentially expressed genes (DEGs) were screened using the GSE106680, GSE97537, and GSE61616 datasets, and hub genes were identified through construction of protein-protein interaction networks.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!