Dopaminergic lesion enhances growth factor-induced striatal neuroblast migration.

• Adult neurogenesis persists in the subventricular zone and is decreased in Parkinson disease (PD). The therapeutic potential of neurogenesis in PD requires understanding of mechanisms of 1) neural stem cell generation; 2) their guidance to the lesion site; and 3) the environment that enables neuronal differentiation, survival, and functional integration. We examined the combined intraventricular infusion of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF-2) in a 6-hydroxydopamine-induced rodent model of PD. Epidermal growth factor and FGF-2 induced a massive increase in cell proliferation and in numbers of doublecortin-expressing neuroblasts in the subventricular zone. These growth factors also increased dopaminergic neurogenesis in the olfactory bulb and promoted the migration of newly generated neuroblasts from the subventricular zone into the adjacent striatum. The effects of EGF and FGF-2 were present in unlesioned animals but were dramatically enhanced in 6-hydroxydopamine-lesioned animals.These findings suggest that newly generated neuroblasts may be redirected to the region of dopaminergic deficit, and that EGF and FGF-2 can enhance dopaminergic neurogenesis in the olfactory bulb but not in the striatum. Similar mechanisms may be involved in the increased numbers of dopaminergic neurons observed in the olfactory bulbs of PD patients and their functional olfactory deficits.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

Animals

Brain Injuries

chemically induced

drug therapy

pathology

physiopathology

Cell Count

Cell Differentiation

drug effects

Cell Movement

drug effects

physiology

Cell Proliferation

drug effects

Corpus Striatum

drug effects

pathology

Disease Models

Animal

Dopamine

metabolism

Female

In Situ Nick-End Labeling

Intercellular Signaling Peptides and Proteins

administration & dosage

Nerve Tissue Proteins

metabolism

Neurons

drug effects

physiology

Oxidopamine

Rats

Rats

Wistar

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)