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Göteborgs universitets publikationer

Striatal deafferentation increases dopaminergic neurogenesis in the adult olfactory bulb.

Författare och institution:
Beate Winner (-); Martin Geyer (-); Sebastien Couillard-Despres (-); Robert Aigner (-); Ulrich Bogdahn (-); Ludwig Aigner (-); Hans-Georg Kuhn (Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering); Jürgen Winkler (-)
Publicerad i:
Experimental neurology, 197 ( 1 ) s. 113-21
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Dopaminergic loss is known to be one of the major hallmarks of Parkinson disease (PD). In addition to its function as a neurotransmitter, dopamine plays significant roles in developmental and adult neurogenesis. Both dopaminergic deafferentation and stimulation modulate proliferation in the subventricular zone (SVZ)/olfactory bulb system as well as in the hippocampus. Here, we study the impact of 6-hydroxydopamine (6-OHDA) lesions to the medial forebrain bundle on proliferation and neuronal differentiation of newly generated cells in the SVZ/olfactory bulb axis in adult rats. Proliferation in the SVZ decreased significantly after dopaminergic deafferentation. However, the number of neural progenitor cells expressing the proneuronal cell fate determinant Pax-6 increased in the SVZ. Survival and quantitative cell fate analysis of newly generated cells revealed that 6-OHDA lesions induced opposite effects in the two different regions of neurogenesis in the olfactory bulb: a transient decrease in the granule cell layer contrasts to a sustained increase of newly generated neurons in the glomerular layer. These data point towards a shift in the ratio of newly generated interneurons in the olfactory bulb layers. Dopaminergic neurogenesis in the glomerular layer tripled after lesioning and consistent with this finding, the total number of tyrosine hydroxylase (TH)-positive cells increased. Thus, loss of dopaminergic input to the SVZ led to a distinct cell fate decision towards stimulation of dopaminergic neurogenesis in the olfactory bulb glomerular layer. This study supports the accumulating evidence that neurotransmitters play a crucial role in determining survival and differentiation of newly generated neurons.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Animals, Antimetabolites, pharmacology, Apoptosis, physiology, Bromodeoxyuridine, pharmacology, Cell Count, Cell Survival, physiology, Cerebral Ventricles, cytology, physiology, Denervation, Dopamine, physiology, Eye Proteins, genetics, Female, Fluorescent Antibody Technique, Homeodomain Proteins, genetics, Immunohistochemistry, Neostriatum, cytology, physiology, Neurons, Afferent, physiology, Olfactory Bulb, cytology, physiology, Oxidopamine, Paired Box Transcription Factors, genetics, Rats, Rats, Wistar, Repressor Proteins, genetics, Sympathectomy, Chemical, Sympatholytics
Postens nummer:
Posten skapad:
2009-01-13 12:59
Posten ändrad:
2011-01-20 09:59

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