@article{discovery1554123,
          volume = {121},
           title = {Targeting glutamatergic and cellular prion protein mechanisms of amyloid {\ensuremath{\beta}}-mediated persistent synaptic plasticity disruption: longitudinal studies},
           pages = {231--246},
            note = {This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.},
           month = {July},
            year = {2017},
         journal = {Neuropharmacology},
        keywords = {APP transgenic rat, Alzheimer's disease, Glutamate-oxalate transaminase, Long-term potentiation, Metabotropic glutamate receptor 5},
        abstract = {Alzheimer's disease amyloid-{\ensuremath{\beta}} (A{\ensuremath{\beta}}) oligomers are synaptotoxic, inappropriately increasing extracellular glutamate concentration and glutamate receptor activation to thereby rapidly disrupt synaptic plasticity. Thus, acutely promoting brain glutamate homeostasis with a blood-based scavenging system, glutamate-oxaloacetate transaminase (GOT), and blocking metabotropic glutamate 5 (mGlu5) receptor or its co-receptor cellular prion protein (PrP), prevent the acute inhibition of long-term potentiation (LTP) by exogenous A{\ensuremath{\beta}}. Here, we evaluated the time course of the effects of such interventions in the persistent disruptive effects of A{\ensuremath{\beta}} oligomers, either exogenously injected in wild type rats or endogenously generated in transgenic rats that model Alzheimer's disease amyloidosis. We report that repeated, but not acute, systemic administration of recombinant GOT type 1, with or without the glutamate co-substrate oxaloacetate, reversed the persistent deleterious effect of exogenous A{\ensuremath{\beta}} on synaptic plasticity. Moreover, similar repetitive treatment reversibly abrogated the inhibition of LTP monitored longitudinally in freely behaving transgenic rats. Remarkably, brief repeated treatment with an mGlu5 receptor antagonist, basimglurant, or an antibody that prevents A{\ensuremath{\beta}} oligomer binding to PrP, ICSM35, also had similar reversible ameliorative effects in the transgenic rat model. Overall, the present findings support the ongoing development of therapeutics for early Alzheimer's disease based on these complementary approaches.},
            issn = {1873-7064},
             url = {https://doi.org/10.1016/j.neuropharm.2017.03.036},
          author = {Zhang, D and Qi, Y and Klyubin, I and Ondrejcak, T and Sarell, CJ and Cuello, AC and Collinge, J and Rowan, MJ}
}