PMU-Autor/inn/en
Aigner LudwigAbstract
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 ill 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. (c) 2005 Elsevier Inc. All rights reserved.
Useful keywords (using NLM MeSH Indexing)
Animals
Antimetabolites/pharmacology
Apoptosis/physiology
Bromodeoxyuridine/pharmacology
Cell Count
Cell Survival/physiology
Cerebral Ventricles/cytology
Cerebral Ventricles/physiology
Denervation
Dopamine/physiology*
Eye Proteins/genetics
Female
Fluorescent Antibody Technique
Homeodomain Proteins/genetics
Immunohistochemistry
Neostriatum/cytology*
Neostriatum/physiology*
Neurons, Afferent/physiology*
Olfactory Bulb/cytology*
Olfactory Bulb/physiology*
Oxidopamine
Paired Box Transcription Factors/genetics
Rats
Rats, Wistar
Repressor Proteins/genetics
Sympathectomy, Chemical
Sympatholytics
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