Reactive Astrocytes Are Key Players in Nigrostriatal Dopaminergic Neurorepair in the Mptp Mouse Model of Parkinson’s Disease: Focus on Endogenous Neurorestoration
Francesca L.’ Episcopo, Cataldo Tirolo, Nuccio Testa, Salvo Caniglia, Maria Concetta Morale and Bianca Marchetti
Pages 45-55 (11)
Parkinsons’disease (PD), a common neurodegenerative disorder, is characterized by progressive loss of dopaminergic
(DAergic) neurons in the subtantia nigra pars compacta (SNpc) and gliosis. The cause and mechanisms underlying
the demise of nigrostriatal DAergic neurons are not completely clarified, but interactions between genes and environmental
factors are recognized to play a critical role in modulating the vulnerability to PD. Current evidence points to reactive
glia as a pivotal factor in PD, but whether astroglia activation may protect or exacerbate DAergic neuron loss is presently
the subject of much debate. Astrocytes and microglia are the key players in neuroinflammatory responses, by secreting
an array of pro- and anti-inflammatory cytokines, anti-oxidant and neurotrophic factors. Here, the contribution of astrocytes
and their ability to influence DAergic neurodegeneration, neuroprotection and neurorepair will be discussed. In
particular, the dynamic interplay between astrocyte-derived factors and neurogenic signals in MPTP-induced plasticity of
nigrostriatal DAergic neurons will be summarized together with recent findings showing that reactive astrocytes may contribute
to promote DAergic neurogenesis from midbrain adult neural stem/precursor cells (NPCs). Within a host of astrocyte-
derived factors, we unveiled Wingless-type MMTV integration site (Wnt)/β-catenin signalling was unveiled, as a
strong candidate in MPTP-induced DAergic neuroplasticty/neurorepair. Understanding the intrinsic plasticity of nigrostriatal
DAergic neurons and decifering the signals facilitating the crosstalk between astrocytes and midbrain neuroprogenitors
may have implications for the role of stem cells technology in PD and for identifying potential therapeutic targets to
promote endogenous neurorepair.
Astrocytes, dopaminergic neurons, neurodegeneration, neurogenesis, neuroprotection, Parkinson’s disease.
Department of Clinical and Molecular Biomedicine, University of Catania and Lab Head at the OASI Institute for Research and Care on Mental Retardation and Brain Aging (IRCCS), Section of Neuropharmacology, Via Conte Ruggero 73, 94018 Troina (EN) Italy.