P4‐034: Udp Attenuates Beta‐amyloid Burden and Reverses the Deficit of Long Term Potentiation in Psapp Animals
Year: 2010
Type: article
Abstract: Accumulation of beta-amyloid peptide is a defining feature of Alzheimer's disease (AD) and shows a strong correlation with the degree of neurological dysfunction. It has been suggested that microglial phagocytosis of beta-amyloid deposits is a major clearance pathway in AD pathology. Uridine diphosphate (UDP) has been shown to trigger microglial phagocytosis through activation of metabotropic purinergic receptor P2Y6. In the present study, we evaluate the effect of acute intraventricular administration of UDP on plaque burden in PSAPP transgenic animals. Using two-photon in vivo imaging, amyloid plaques labeled by methoxy-x04 were imaged in the barrel cortex through a thinned skull. Immediately following one pre-treatment imaging session, UDP or vehicle were injected intracerebroventricularly and three days later images were obtained from the same area using identical imaging parameters. Brains were subjected to long term potentiation recording or were subsequently fixed, sectioned and examined histologically. Treatment with UDP led to a 12.6 % (p < 0.05) reduction in the number of plaques and a 17.2 % (p < 0.05) reduction in area occupied by plaques as assessed by two-photon microscopy. Individually identified plaques that were detected on the second imaging session showed an 18.2% reduction in cross-sectional area following UDP treatment which was significantly (P < 0.0001) reduced compared to vehicle injection. Post-hoc staining also demonstrated that UDP treatment reduced the plaque burden. PSAPP mice injected with UDP displayed fewer β1-42 and β1-40 labeled plaque and thioflavinS labeled dense core in both cortex and hippocampus. We further showed that acute UDP treatment reversed the deficits in long term potentiation (LTP) in hippocampal Schaffer collateral pathway in PSAPP mice. Moreover, we showed that UDP treatment improved cognitive behavior of PSAPP mice in fear conditioning test. Taken together, this study leads us to conclude that UDP, potentially acting through P2Y6 receptors, stimulates plaque clearance, which might contribute to the improvement of cognitive behavior of PSAPP mice.
Source: Alzheimer s & Dementia
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2037028978