Biology subjects

Kecheliev, V.

Publications and source records attributed to Kecheliev, V..

2 recordsLinked to original sources

bioRxiv2022

Evaluation of CB2R expression and pyridine-based radiotracers in brains from a mouse model of Alzheimer's disease

Neuroinflammation plays an important role in the pathophysiology of Alzheimers disease. The cannabinoid type 2 receptor (CB2R) is an emerging target for neuroinflammation and therapeutics of Alzheimers disease. Here, we aimed to assess the alterations in brain CB2R levels and evaluate novel CB2R imaging tracers in the arcA{beta} mouse model of Alzheimers disease amyloidosis. Immunohistochemical staining for A{beta} deposits (6E10), microgliosis (anti-Iba1 and anti-CD68 antibodies), astrocytes (GFAP) and the anti-CB2R antibody was performed on brain slices from arcA{beta} mice 17 months of age. Autoradiography using the CB2R imaging probes [18F]RoSMA-18-d6, [11C]RSR-056 and [11C]RS-028 and mRNA analysis were performed in brain tissue from arcA{beta} and nontransgenic littermate (NTL) mice at 6, 17, and 24 months of age. Specific increased CB2R immunofluorescence intensities on the increased number of GFAP-positive astrocytes and Iba1-positive microglia were detected in the hippocampus and cortex of 17-month-old arcA{beta} mice compared to NTL mice. CB2R immunofluorescence was higher in the glial cells inside 6E10-positive amyloid-{beta} deposits than peri-plaque with a low background. Ex vivo autoradiography showed that the binding of [18F]RoSMA-18-d6 and [11C]RSR-056 was comparable in arcA{beta} and NTL mice at 6, 17 and 24 months. The level of Cnr2 mRNA expression in the brain was not significantly different between arcA{beta} and NTL mice at 6, 17 or 24 months. In conclusion, we demonstrated pronounced specific increases in microglial and astroglial CB2R expression levels in a model of AD-related cerebral amyloidosis/AD mouse model, emphasizing CB2R as a suitable target for imaging neuroinflammation.

neuroscience↗

bioRxiv2022

Aquaporin 4 is differentially increased and depolarized in association with tau and amyloid-beta

Neurovascular-glymphatic dysfunction plays an important role in Alzheimers disease and has been analyzed mainly in association with amyloid-beta (A{beta}) pathology. The neurovascular-glymphatic link with tauopathies has not been well elucidated. Here, we aimed to investigate the alterations in the neurovasculature and map the aquaporin 4 (AQP4) distribution and depolarization associated with tau and A{beta}. Perfusion, susceptibility weighted imaging and structural magnetic resonance imaging (MRI) were performed in the pR5 P301L mouse model of 4-repeat tau and the arcA{beta} mouse model of amyloidosis. Immunofluorescence staining was performed using antibodies against AQP4, CD31, astroglia (GFAP, s100{beta}), phospho-tau (AT-8) and A{beta} (6E10) in brain tissue slices from P301L, arcA{beta} and nontransgenic mice. P301L mice showed regional atrophy, preserved cerebral blood flow and reduced cerebral vessel density compared to nontransgenic mice, while arcA{beta} mice showed cerebral microbleeds and reduced cerebral vessel density. AQP4 depolarization and peri-tau enrichment in the hippocampus and increased AQP4 levels in the forebrain and hippocampus were detected in P301L mice compared to nontransgenic mice. In comparison, cortical AQP4 depolarization and cortical/hippocampal peri-plaque increases were observed in arcA{beta} mice. Increased s100{beta}-GFAP fluorescence intensities indicative of reactive astrocytes were detected surrounding tau inclusions in P301L mice and A{beta} plaques in arcA{beta} mice. In conclusion, we observed a divergent region-specific AQP4 increase and association with phospho-tau and A{beta} pathologies.

neuroscience↗