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Striatal deafferentation increases dopaminergic neurogenesis in the adult olfactory bulb.

Artikel i vetenskaplig tidskrift
Författare Beate Winner
Martin Geyer
Sebastien Couillard-Despres
Robert Aigner
Ulrich Bogdahn
Ludwig Aigner
Hans-Georg Kuhn
Jürgen Winkler
Publicerad i Experimental neurology
Volym 197
Nummer/häfte 1
Sidor 113-21
ISSN 0014-4886
Publiceringsår 2006
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering
Sidor 113-21
Språk en
Länkar dx.doi.org/10.1016/j.expneurol.2005...
Ämnesord 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
Ämneskategorier Medicin och Hälsovetenskap

Sammanfattning

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.

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