There are reports of P2Y1 receptor upregulation in CNS under pathological conditions such as mechanical injury,244 ischemia,245 and neurodegeneration.246 Additionally, hyperactivity of astrocytic P2Y1 receptors have been detected in animal models of AD246,247 and increased expression of the receptor has been observed in hippocampus and cortex of postmortem brain sections in patients with AD.248 P2Y1R is also upregulated after stroke and TBI and inhibition of the receptor has been shown to reduce cognition deficit resulted from these conditions.249 Indeed, antagonists of the P2Y1 receptor have shown to reduce neuronal injury and improve spatial memory in rat model of TBI.250,251
