Parkinson's disease is a neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons in the nigrostriatal projection. Transplantation of fetal dopaminergic precursor cells has paved the way for the possibility of a cell replacement therapy that could ameliorate clinical symptoms in affected patients.
Neural stem cells have been identified in the neurogenic brain regions, where neurogenesis is constitutively ongoing, but also in the non-neurogenic zones, such as the midbrain and the striatum, where neurogenesis is not thought to occur under normal physiological conditions:
A) The ventral midbrain in a rat, stained immunohistochemically for tyrosine hydroxylase (green), comprises the substantia nigra pars compacta (SNc) containing predominantly dopaminergic neurons giving rise to nigrostriatal axons, the substantia nigra pars reticulata (SNr) containing mainly GABAergic neurons and some dopaminergic neurons, and the ventral tegmental area (VTA ) containing mainly dopaminergic neurons giving rise to mesolimbic axons.
B) In Parkinson’s disease and corresponding animal models (here exemplified by a 6-OHDA-lesioned rat), a preferential degeneration of the dopaminergic neurons in the substantia nigra with relative sparing of theVTA is observed.
C) In the parenchyma of the normal adult ventral midbrain, presence of neural stem cells (NSCs) has been reported, which unfold their neurogenic potential once explanted and stimulated with appropriate cues in vitro.
D) In vivo, however, the neurogenic potential of the adult parenchymal NSCs in the ventral midbrain appears to be restricted by presently unidentified inhibiting cues (flashes), which might be emitted for example by local glial cells or mature neurons, rendering the substantia nigra in the adult brain a primarily non-neurogenic area.
A detailed understanding of the factors governing adult neural stem cells in vivo may ultimately lead to elegant cell therapies for neurodegenerative disorders such as Parkinson's disease by mobilizing autologous endogenous neural stem cells to replace degenerated neurons.
References
Arias-Carrión O, Yamada E, Freundlieb N, Djufri M, Maurer L, Hermanns G, Ipach B, Chiu WH, Steiner C, Oertel WH, Höglinger GU. Neurogenesis in substantia nigra of Parkinsonian brains? J Neural Transm Suppl 73:279-85 (2009)
Depboylu C, Schäfer MKH, Arias-Carrión O, Oertel WH, Weihe E, Höglinger GU. Possible Involvement of complement factor C1q in the clearance of extracellular neuromelanin from the substantia nigra in Parkinson’s disease. J Neuropathol Exp Neurol 70 (2) 125-132 (2011)
Arias-Carrión O, Freundlieb N, Oertel WH, Höglinger GU. Adult Neurogenesis and Parkinson’s disease. CNS Neurol Disord Drug Targets 6:326-35 (2007)
Neural stem cells have been identified in the neurogenic brain regions, where neurogenesis is constitutively ongoing, but also in the non-neurogenic zones, such as the midbrain and the striatum, where neurogenesis is not thought to occur under normal physiological conditions:
A) The ventral midbrain in a rat, stained immunohistochemically for tyrosine hydroxylase (green), comprises the substantia nigra pars compacta (SNc) containing predominantly dopaminergic neurons giving rise to nigrostriatal axons, the substantia nigra pars reticulata (SNr) containing mainly GABAergic neurons and some dopaminergic neurons, and the ventral tegmental area (
B) In Parkinson’s disease and corresponding animal models (here exemplified by a 6-OHDA-lesioned rat), a preferential degeneration of the dopaminergic neurons in the substantia nigra with relative sparing of the
C) In the parenchyma of the normal adult ventral midbrain, presence of neural stem cells (NSCs) has been reported, which unfold their neurogenic potential once explanted and stimulated with appropriate cues in vitro.
D) In vivo, however, the neurogenic potential of the adult parenchymal NSCs in the ventral midbrain appears to be restricted by presently unidentified inhibiting cues (flashes), which might be emitted for example by local glial cells or mature neurons, rendering the substantia nigra in the adult brain a primarily non-neurogenic area.
A detailed understanding of the factors governing adult neural stem cells in vivo may ultimately lead to elegant cell therapies for neurodegenerative disorders such as Parkinson's disease by mobilizing autologous endogenous neural stem cells to replace degenerated neurons.
References
Arias-Carrión O, Yamada E, Freundlieb N, Djufri M, Maurer L, Hermanns G, Ipach B, Chiu WH, Steiner C, Oertel WH, Höglinger GU. Neurogenesis in substantia nigra of Parkinsonian brains? J Neural Transm Suppl 73:279-85 (2009)
Depboylu C, Schäfer MKH, Arias-Carrión O, Oertel WH, Weihe E, Höglinger GU. Possible Involvement of complement factor C1q in the clearance of extracellular neuromelanin from the substantia nigra in Parkinson’s disease. J Neuropathol Exp Neurol 70 (2) 125-132 (2011)
Arias-Carrión O, Freundlieb N, Oertel WH, Höglinger GU. Adult Neurogenesis and Parkinson’s disease. CNS Neurol Disord Drug Targets 6:326-35 (2007)
