Elsevier

Neuroscience

Volume 95, Issue 2, December 1999, Pages 425-432
Neuroscience

The absence of reactive astrocytosis is indicative of a unique inflammatory process in Parkinson's disease

https://doi.org/10.1016/S0306-4522(99)00455-8Get rights and content

Abstract

Virtually any neurological disorder leads to activation of resident microglia and invasion of blood-borne macrophages, which are accompanied by an increase in number and change in phenotype of astrocytes, a phenomenon generally termed reactive astrocytosis. One of the functions attributed to activation of astrocytes is thought to involve restoration of tissue damage. Hitherto, the role of astrocytes in the inflammatory reaction occurring in Parkinson's disease has not received much attention. In the present study, we examined the inflammatory events in autopsies of the substantia nigra and putamen from Parkinson's disease patients using age-matched autopsies from normal patients as controls. In the substantia nigra, activation of microglia was consistently observed in all Parkinson's disease autopsies as verified from immunohistochemical detection of CR3/43 and ferritin. Activation of resident microglia was not observed in the putamen. No differences were observed between controls and Parkinson's disease autopsies from the substantia nigra and putamen, in terms of distribution, cellular density or cellular morphology of astrocytes stained for glial fibrillary acidic protein or metallothioneins I and II, the latter sharing high affinity for metal ions and known to be induced in reactive astrocytes, possibly to exert anti-oxidative effects.

Together, these findings indicate that the inflammatory process in Parkinson's disease is characterized by activation of resident microglia without reactive astrocytosis, suggesting that the progressive loss of dopaminergic neurons in Parkinson's disease is an ongoing neurodegenerative process with a minimum of involvement of the surrounding nervous tissue. The absence of reactive astrocytosis in Parkinson's disease contrasts what follows in virtually any other neurological disorder and may indicate that the inflammatory process in Parkinson's disease is a unique phenomenon.

Section snippets

Tissue sources

Brain samples of the SN and putamen from PD (n=5) and control subjects (n=5) were obtained from the Netherlands Brain Bank (Amsterdam, The Netherlands). Control samples were obtained among patients without previous neurological disease before death and no pathological changes in sections of the SNpc. The post mortem interval from the time of death until fixation was less than 24 h in all cases (Table 1). The samples were obtained from brains fixed in formalin and embedded in paraffin.

The

Results

The normal and PD cases did not differ significantly with respect to age and brain weight (Table 1). Likewise, the post mortem fixation delay and the pH values of cerebrospinal fluid sampled post mortem did not display significant differences (Table 1), indicating that the material employed for the study was of equal quality with respect to the potential risk of post mortem autolysis of the tissue.

Discussion

Our results show that astrocytes, in contrast to microglial cells, did not display signs of inflammation in the chronic settings of degenerating DA neurons in the SN of patients clinically and pathologically diagnosed with PD. MTs I and II were not up-regulated in astrocytes in PD cases in terms of cellular distribution or increased labelling intensity.

Conclusion

In PD, the SN harbours numerous cells of the myelo-monocytic lineage. Judging from the morphology of these cells, they represent residing, activated microglia rather than invading monocytes or macrophages. The microgliosis is not accompanied by activation of GFAP-containing astrocytes in PD autopsies. Supporting this observation, MTs I and II are not up-regulated in astrocytes. In the putamen, we did not find any inflammatory changes such as microgliosis or reactive astrocytosis. The absence of

Acknowledgements

The excellent technical assistance of Birgit Risto is greatly appreciated. This work was supported by The Mette and Mogens Mogensens Fund.

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