Abnormal compartmentalization of norepinephrine in mouse dentate gyrus in alpha-synuclein knockout and A30P transgenic mice.
In the dentate gyrus of the mouse hippocampus, presynaptic recruitment of norepinephrine in response to repeated-burst stimulation can be described in terms of an interaction between storage and readily releasable pools. The dynamics of this interaction depends on neuronal activity (bursting), so that the higher the demand for norepinephrine, the faster it is delivered from the storage pool. We also found that alpha-synuclein, a presynaptic protein that plays a crucial role in dopamine compartmentalization in the striatum, is also involved in the compartmentalization of norepinephrine in the dentate gyrus. Experiments in transgenic mice with modified or absent alpha-synuclein revealed that the familial Parkinson's disease-linked alpha-synuclein mutation A30P can cause selective changes in the function of noradrenergic terminals. Addition of mutated human alpha-synuclein abolished the normal norepinephrine mobilization. There were no compensatory mechanisms available in the norepinephrine presynaptic terminals. In contrast, deletion of mouse alpha-synuclein is compensated for by increased vesicle transport from the storage pool. The effects are essentially the same as previously reported for dopaminergic terminals in the striatum, indicating that the important role of alpha-synuclein in neurotransmitter mobilization is not limited to dopaminergic terminals.
Yavich
Leonid
L
Department of Pharmacology and Toxicology, University of Kuopio, Finland. Leonid.Yavich@uku.fi
Jäkälä
Pekka
P
Tanila
Heikki
H
D000818:Animals; D003627:Data Interpretation, Statistical; D018891:Dentate Gyrus / Q000378:metabolism* / Q000502:physiology; D004558:Electric Stimulation; D004563:Electrochemistry; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology*; D017072:Neostriatum / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism* / Q000502:physiology; D017729:Presynaptic Terminals / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism*
D018341:Receptors, Adrenergic, alpha-2; D051844:alpha-Synuclein; D009638:Norepinephrine