Neurology -- Correspondence for Migliore et al., 58 (12) 1809-1815

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Correspondence published:

Reply to Letter to the Editor: U Bonucelli, C Lucetti, G Gambaccini, L. Petrozzi, and L. Migiliore (23 October 2002)

Oxidative damage and cytogenetic analysis in leukocytes of Parkinson’s disease patients: Gabriele Neurauter, Friedrich Leblhuber, Dietmar Fuchs (12 September 2002)

Reply to Letter to the Editor 23 October 2002

U Bonucelli
University of Pisa Italy,
C Lucetti, G Gambaccini, L. Petrozzi, and L. Migiliore
Send Correspondence to journal:
Re: Reply to Letter to the Editor

u.bonuccelli{at}med.unipi.it U Bonucelli, et al.

In our study the occurrence of DNA oxidative damage outside the CNS supports the hypothesis that a systemic derangement parallels neural abnormalities in patients with PD; this suggests that PD is a systemic disorder, even if the principal target of the damage is the CNS. [1] Moreover, there are evidences of immune activation in peripheral blood [2] and in CNS of patients with PD: glial reaction, increased expression of cytokines and components of complement have been reported in the brain of PD. [3]
All these findings lead to the hypothesis of immune reaction and consequent inflammation as a common mechanism contributing to the pathogenesis of neurodegeneration: this is well demonstrated in AD where inflammatory reactions are thought to be important contributors to the neuronal loss. [8] The deleterious effect of inflammation is potentially of great importance because it may point to target for possible therapeutic intervention. However, it is not know whether inflammation and oxidative stress play a central role or represent only an epiphenomenon in neuronal death of patients with PD.
The hypothesis that oxidative stress, developing in the peripheral blood as a result of immune activation, could contribute to the depletion of antioxidants in the brain is intriguing but needs more evidences. For what we known most available natural antioxidants do not cross the blood brain barrier. [5]
References:
1. Migliore L, Petrozzi L, Lucetti C, et al. Oxidative damage and cytogenetic analysis in leukocytes of Parkinson's disease patients. Neurology 2002;58:1809-1815.
2. Hisanaga K, Asagi M, Itoyama Y, Iwasaki Y. Increase in peripheral CD4 bright+ CD8 dull+ T cells in Parkinson disease. Arch Neurol 2001;58:1580-1583.
3. Członkowska A, Kurkowska-Jastrzębska I, Członkowski A, et al. Immune processes in the pathogenesis of Parkinson’s disease – a potential role for microglia and nitric oxide. Med Sci Monit 2002;8:165-177.
4. McGeer PL, McGeerEG. Mechanisms of cell death in Alzheimer disease -immunopathology. J Neural Transm Suppl 1998;54:159-166.
5. Gilgun-Sherki Y, Melamed E, Offen D. Oxidative stress induced- neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier. Neuropharmacology 2001;40:959-975.

Oxidative damage and cytogenetic analysis in leukocytes of Parkinson’s disease patients 12 September 2002

Gabriele Neurauter,
Research assistant
University of Innsbruck,
Friedrich Leblhuber, Dietmar Fuchs
Send Correspondence to journal:
Re: Oxidative damage and cytogenetic analysis in leukocytes of Parkinson’s disease patients

gabrile.neurauter{at}uibk.ac.at Gabriele Neurauter, et al.

We read with interest the recent article by Migliore et al. [1] in which oxidative damage was shown in lymphocytes of untreated patients with PD. This study confirms other data regarding abnormalities detectable outside the brains of patients and confirms chronic activation status of leukocytes as indicated by, for example, higher blood concentrations of tumor necrosis factor-a. [2] Other features of immune activation like accelerated neopterin production or degradation of tryptophan were described and correlate with, for example, Hoehn & Yahr stages. [3] Both neopterin production and degradation of tryptophan are inducible by interferon-g and thus coincide with cell-mediated (Th-1 type) immune activation. Finally, accumulation of homocysteine was reported in the blood of patients with PD and homocysteine concentrations correlated with the degree of immune activation. [4] Changes in neopterin and homocysteine concentrations and of tryptophan degradation were observed in the brain of patients, but changes seen in the peripheral blood were more significant.
These data could represent an epiphenomenon, but could also indicate that immune activation outside the brain may somehow contribute to the pathogenesis of this neurodegenerative disease, the pathology of which is confined to brain tissue. Activation of immunocompetent cells like T-lymphocytes and macrophages is associated with the production of huge amounts of oxidizing compounds, thereby oxidative stress develops in the peripheral blood. This could then contribute to depletion of antioxidants which then are also less available across the blood-brain-barrier.
References
1. Migliore L, Petrozzi L, Lucetti C, et al. Oxidative damage and cytogenetic analysis in leukocytes of Parkinson's disease patients. Neurology 2002;58:1809-1815.
2. Dobbs RJ, Charlett A, Purkiss AG, Dobbs SM, Weller C, Peterson DW. Association of circulating TNF-alpha and IL-6 with ageing and parkinsonism. Acta Neurol Scand 1999;100:34-41.
3. Widner B, Leblhuber F, Fuchs D. Increased neopterin production and tryptophan degradation in advanced Parkinson’s disease. J Neural Transm 2002;109:181-189.
4. Kuhn W, Roebroek R, Blom H, van Oppenraaij D, Müller T. Hyperhomocysteinaemia in Parkinson's disease. J Neurol 1998;245: 811-812.
5. Widner B, Leblhuber F, Frick B, Laich A, Artner-Dworzak E, Fuchs D. Moderate hyperhomocysteinaemia and immune activation in Parkinson’s disease. J Neural Transm (in press).