Abstract
The role of astrocytes in Parkinson’s disease is still not well understood. This work studied the astrocytic response to the dopaminergic denervation. Rats were injected in the lateral ventricles with 6-hydroxydopamine (25μg), inducing a dopaminergic denervation of the striatum not accompanied by non-selective tissue damage. The dopaminergic debris were found within spheroids (free-spheroids) which retained some proteins of dopaminergic neurons (e.g., tyrosine hydroxylase, the dopamine transporter protein, and APP) but not others (e.g., α-synuclein). Free-spheroids showed the initial (LC3-autophagosomes) but not the late (Lamp1/Lamp2-lysosomes) components of autophagy (incomplete autophagy), preparing their autophagosomes for an external phagocytosis (accumulation of phosphatidylserine). Free-spheroids were penetrated by astrocyte processes (fenestrated-spheroids) which made them immunoreactive for GFAP and S100β, and which had some elements needed to continue the debris degradation (Lamp1/Lamp2). Finally, proteins normally found in neurons (TH, DAT and α-synuclein) were observed within astrocytes 2–5 days after the dopaminergic degeneration, suggesting that the intracellular contents of degenerated cells had been transferred to astrocytes. Taken together, present data suggest phagocytosis as a physiological role of striatal astrocytes, a role which could be critical for cleaning striatal debris during the initial stages of Parkinson’s disease.
Highlights
There is increasing evidence suggesting that the degeneration of dopamine neurons (DA-ergic neurons) which characterizes Parkinson’s disease (PD) starts in the striatal synapse and progresses by dying-back degeneration of the axon to the cell soma in the substantia nigra (SN) [1]
As shown on the right-side of Panel D4 in Fig 1, both the tyrosine hydroxylase (TH) and amyloid precursor protein (App) were distributed across the spheroid
Syn immunoreactivity was some time found in the extracellular space near fragmented axons (Panels E1-E3 in Fig 1), no statistical difference was found for Syn immunoreactivity inside vs. outside the spheroid
Summary
There is increasing evidence suggesting that the degeneration of dopamine neurons (DA-ergic neurons) which characterizes Parkinson’s disease (PD) starts in the striatal synapse and progresses by dying-back degeneration of the axon to the cell soma in the substantia nigra (SN) [1]. DA-ergic neurons present a slow degeneration with aging Striatal astrocytes have been involved in the starting and progression of PD but, because astrocytes may increase [8, 11, 14] and prevent [15,16,17,18] the neuronal damage, their actual role in the DA-ergic neuron degeneration is controversial [19]
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