TY - JOUR
T1 - α-Synuclein involvement in hippocampal synaptic plasticity
T2 - Role of NO, cGMP, cGK and CaMKII
AU - Liu, Shumin
AU - Fa, Mauro
AU - Ninan, Ipe
AU - Trinchese, Fabrizio
AU - Dauer, William
AU - Arancio, Ottavio
PY - 2007/6
Y1 - 2007/6
N2 - Synaptic plasticity involves a series of coordinate changes occurring both pre- and postsynaptically, of which α-synuclein is an integral part. We have investigated on mouse primary hippocampal neurons in culture whether redistribution of α-synuclein during plasticity involves retrograde signaling activation through nitric oxide (NO), cGMP, cGMP-dependent protein kinase (cGK) and calmodulin-dependent protein kinase II. We have found that deletion of the α-synuclein gene blocks both the long-lasting enhancement of evoked and miniature transmitter release and the increase in the number of functional presynaptic boutons evoked through the NO donor, DEA/NO, and the cGMP analog, 8-Br-cGMP. In agreement with these findings both DEA/NO and 8-Br-cGMP were capable of producing a long-lasting increase in number of clusters for α-synuclein through activation of soluble guanylyl cyclase, cGK and calcium/calmodulin-dependent protein kinase IIα. Thus, our results suggest that NO, cGMP, GMP-dependent protein kinase and calmodulin-dependent protein kinase II play a key role in the redistribution of α-synuclein during plasticity.
AB - Synaptic plasticity involves a series of coordinate changes occurring both pre- and postsynaptically, of which α-synuclein is an integral part. We have investigated on mouse primary hippocampal neurons in culture whether redistribution of α-synuclein during plasticity involves retrograde signaling activation through nitric oxide (NO), cGMP, cGMP-dependent protein kinase (cGK) and calmodulin-dependent protein kinase II. We have found that deletion of the α-synuclein gene blocks both the long-lasting enhancement of evoked and miniature transmitter release and the increase in the number of functional presynaptic boutons evoked through the NO donor, DEA/NO, and the cGMP analog, 8-Br-cGMP. In agreement with these findings both DEA/NO and 8-Br-cGMP were capable of producing a long-lasting increase in number of clusters for α-synuclein through activation of soluble guanylyl cyclase, cGK and calcium/calmodulin-dependent protein kinase IIα. Thus, our results suggest that NO, cGMP, GMP-dependent protein kinase and calmodulin-dependent protein kinase II play a key role in the redistribution of α-synuclein during plasticity.
KW - Cell culture
KW - Immunoreactive clusters
KW - Mouse
KW - Synaptic plasticity
KW - Vesicle cycling
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U2 - 10.1111/j.1460-9568.2007.05569.x
DO - 10.1111/j.1460-9568.2007.05569.x
M3 - Article
C2 - 17610578
AN - SCOPUS:34347387566
SN - 0953-816X
VL - 25
SP - 3583
EP - 3596
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 12
ER -