Gene expression profile at single nucleus level of hippocampal cells from APP-TG mice treated with THC and Cel

Delta-9-tetrahydrocannabinol (?9-THC) is reported to rescue cognitive and synaptic functions in Alzheimer's disease (AD) mice model. However, ?9-THC treatment resulted in neuroinflammation via activating Cox2 in the brain. Our hypothesis is that inhibiting cox2 via celecoxib treatment could inhibit neuroinflammation and enhance the neuroprotective effects of ?9-THC. Our results indicated that Cel-THC treatment inhibited spatial learning and memory impairments of APP-TG mice via water maze test. To investigate the molecular mechanisms, we performed single nucleus RNA sequence of hippocampal cells from WT-Veh, APP-TG-Veh, APP-TG-THC, APP-TG-Cel, and APP-TG-Cel-THC groups. Our results showed that Cel-THC treatment reversed changes of synaptic, inflammation-, and AD-related differentially expressed genes caused by beta amyloid accumulation. Overall design: Single nucleus transcriptomics of hippocampus from WT and transgenic mice were analyzed by snRNA-seq.