Striatal deafferentation increases dopaminergic neurogenesis in the adult olfactory bulb.

• 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.

Nyckelord

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

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