Antonio de Iure1,2, Petra Mazzocchetti1, Guendalina Bastioli1, Barbara Picconi2,3, Cinzia Costa1, Ivan Marchionni4, Giorgio Casari5, Alessandro Tozzi6, Daniela Pietrobon4,7, Paolo Calabresi1. 1. 1 Neurological Clinic, Department of Medicine, Hospital Santa Maria della Misericordia, University of Perugia, Perugia, Italy. 2. 2 Laboratory of Experimental Neurophysiology, IRCCS San Raffaele Pisana, Rome, Italy. 3. 3 San Raffaele University, Rome, Italy. 4. 4 Department of Biomedical Sciences and Padova Neuroscience Center (PNC), University of Padova, Padova, Italy. 5. 5 Vita Salute San Raffaele and San Raffaele Scientific Institute, Milano, Italy. 6. 6 Department of Experimental Medicine, Section of Physiology and Biochemistry, University of Perugia, Perugia, Italy. 7. 7 CNR Institute of Neuroscience, Padova, Italy.
Abstract
INTRODUCTION: Familial hemiplegic migraine 2 is a pathology linked to mutation of the ATP1A2 gene producing loss of function of the α2 Na+/K+-ATPase (NKA). W887R/+ knock-in (KI) mice are used to model the familial hemiplegic migraine 2 condition and are characterized by 50% reduced NKA expression in the brain and reduced rate of K+ and glutamate clearance by astrocytes. These alterations might, in turn, produce synaptic changes in synaptic transmission and plasticity. Memory and learning deficits observed in familial hemiplegic migraine patients could be ascribed to a possible alteration of hippocampal neuronal plasticity and measuring possible changes of long-term potentiation in familial hemiplegic migraine 2 KI mice might provide insights to strengthen this link. RESULTS: Here we have investigated synaptic plasticity in distinct hippocampal regions in familial hemiplegic migraine 2 KI mice. We show that the dentate gyrus long-term potentiation of familial hemiplegic migraine 2 mice is abnormally increased in comparison with control animals. Conversely, in the CA1 area, KI and WT mice express long-term potentiation of similar amplitude. CONCLUSIONS: The familial hemiplegic migraine 2 KI mice show region-dependent hippocampal plasticity abnormality, which might underlie some of the memory deficits observed in familial migraine.
INTRODUCTION:Familial hemiplegic migraine 2 is a pathology linked to mutation of the ATP1A2 gene producing loss of function of the α2 Na+/K+-ATPase (NKA). W887R/+ knock-in (KI) mice are used to model the familial hemiplegic migraine 2 condition and are characterized by 50% reduced NKA expression in the brain and reduced rate of K+ and glutamate clearance by astrocytes. These alterations might, in turn, produce synaptic changes in synaptic transmission and plasticity. Memory and learning deficits observed in familial hemiplegic migrainepatients could be ascribed to a possible alteration of hippocampal neuronal plasticity and measuring possible changes of long-term potentiation in familial hemiplegic migraine 2 KI mice might provide insights to strengthen this link. RESULTS: Here we have investigated synaptic plasticity in distinct hippocampal regions in familial hemiplegic migraine 2 KI mice. We show that the dentate gyrus long-term potentiation of familial hemiplegic migraine 2 mice is abnormally increased in comparison with control animals. Conversely, in the CA1 area, KI and WT mice express long-term potentiation of similar amplitude. CONCLUSIONS: The familial hemiplegic migraine 2 KI mice show region-dependent hippocampal plasticity abnormality, which might underlie some of the memory deficits observed in familial migraine.