Dopaminergic modulation of neurogenesis in the subventricular zone of the adult brain.
Dopaminergic receptors are expressed on neural precursor cells (NPCs) in the subventricular zone (SVZ) and are known to regulate NPC proliferation and differentiation fate in this region. We now report that this optimally requires the simultaneous activation of both D1-like and D2-like dopaminergic receptors with the agonists Bromocriptine, SKF-38393 and 7-OH-pipat maleate (BSP) in vitro. This is consistent with our previous findings that dopamine stimulates NPC proliferation through an EGF paracrine mechanism within the SVZ. Furthermore this combined dopamine agonist therapy rescues NPC proliferation in the SVZ in the 6-OHDA animal model of PD and importantly significantly increases neuronal differentiation in the olfactory bulb to a greater extent than we showed previously with levodopa. This result has implications for the use of dopaminergic therapies in PD and in the development of such therapies focusing on upregulating SVZ neurogenesis.
O'Keeffe
Gráinne C
GC
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. go215@cam.ac.uk
Barker
Roger A
RA
Caldwell
Maeve A
MA
D053687:Adult Stem Cells / Q000502:physiology; D000818:Animals; D001921:Brain / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000166:cytology; D010300:Parkinson Disease / Q000188:drug therapy; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000819:agonists; D017448:Receptors, Dopamine D2 / Q000819:agonists
D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D004298:Dopamine