Sonic hedgehog is a neuromodulator in the adult subthalamic nucleus.
It is well established that members of the hedgehog family are involved in tissue patterning during development. We herein show that sonic hedgehog signaling molecules are differentially regulated by dopamine depletion in the basal ganglia of adult animals and specifically that sonic hedgehog levels are reduced in an animal model of Parkinson's disease. In addition, we show that sonic hedgehog protein inhibits electrical activity in the subthalamic nucleus, a key element of basal ganglia, within minutes of application. As the subthalamic nucleus is overactive in parkinsonism, we suggest that enhancement of sonic hedgehog signaling in the subthalamic nucleus may be of therapeutic value in Parkinson's disease.
Bezard
Erwan
E
Basal Gang and CNRS UMR 5543, Université Victor Segalen, 33076 Bordeaux Cedex, France. erwan.bezard@umr5543.u-bordeaux2.fr
Baufreton
Jerome
J
Owens
Geraint
G
Crossman
Alan R
AR
Dudek
Hank
H
Taupignon
Anne
A
Brotchie
Jonathan M
JM
D000818:Animals; D002478:Cells, Cultured; D004553:Electric Conductivity; D005917:Globus Pallidus / Q000378:metabolism; D053823:Hedgehog Proteins; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020531:Subthalamic Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D053823:Hedgehog Proteins; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D015534:Trans-Activators