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Increased DJ-1 expression under oxidative stress and in Alzheimer's disease brains.

Baulac S, Lu H, Strahle J, Yang T, Goldberg MS, Shen J, Schlossmacher MG, Lemere CA, Lu Q, Xia W - Mol Neurodegener (2009)

Bottom Line: We found that DJ-1 was expressed early during zebrafish development and throughout adulthood.While a slight reduction in staining for islet-1 positive neurons was observed in both DJ-1 KD and H2O2 treated embryos, the number of apoptotic cells was significantly increased in both KD and H2O2 treated embryos.Therefore, our results strongly suggest that DJ-1 expression is not necessary during zebrafish development but can be induced in zebrafish exposed to oxidative stress and is present in human AD brains.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Harvard University, Boston, MA 02115, USA. wxia@rics.bwh.harvard.edu.

ABSTRACT
Mutations in the DJ-1 gene have been linked to autosomal recessive familial Parkinson's disease. To understand the function of DJ-1, we determined the DJ-1 expression in both zebrafish and post mortem human brains. We found that DJ-1 was expressed early during zebrafish development and throughout adulthood. Knock down (KD) of DJ-1 by injection of morpholino did not cause dramatic morphologic alterations during development, and no loss of dopaminergic neurons was observed in embryos lacking DJ-1. However, DJ-1 KD embryos were more susceptible to programmed cell death. While a slight reduction in staining for islet-1 positive neurons was observed in both DJ-1 KD and H2O2 treated embryos, the number of apoptotic cells was significantly increased in both KD and H2O2 treated embryos. Interestingly, DJ-1 expression was increased in brains of zebrafish under conditions of oxidative stress, indicating that DJ-1 is a part of stress-responsive machinery. Since oxidative stress is one of the major contributors to the development of Alzheimer's disease (AD), we also examined DJ-1 expression in AD brains. Using DJ-1 specific antibodies, we failed to detect a robust staining of DJ-1 in brain tissues from control subjects. However, DJ-1 immunoreactivity was detected in hippocampal pyramidal neurons and astrocytes of AD brains. Therefore, our results strongly suggest that DJ-1 expression is not necessary during zebrafish development but can be induced in zebrafish exposed to oxidative stress and is present in human AD brains.

No MeSH data available.


Related in: MedlinePlus

Enhanced immunostaining of DJ-1 in AD but not control brains. A, B. control brains (n = 9) showed weak or no DJ-1 staining in pyramidal neurons of the CA1, CA2, CA3 sub-regions and the hilus of the dentate gyrus (CA4). C, D. AD brains (n = 6/10) showed DJ-1 immunoreactivity in pyramidal neurons (cytoplasm and neuronal processes) of CA1–4 regions. Magnification: A, C = 4×; B, D = 40×.
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Figure 6: Enhanced immunostaining of DJ-1 in AD but not control brains. A, B. control brains (n = 9) showed weak or no DJ-1 staining in pyramidal neurons of the CA1, CA2, CA3 sub-regions and the hilus of the dentate gyrus (CA4). C, D. AD brains (n = 6/10) showed DJ-1 immunoreactivity in pyramidal neurons (cytoplasm and neuronal processes) of CA1–4 regions. Magnification: A, C = 4×; B, D = 40×.

Mentions: Control brains (n = 9) also showed DJ-1 immunoreactivity in scattered astrocytes (data not shown), but they showed weak or no DJ-1 staining in pyramidal neurons of the CA1, CA2, CA3 sub-regions and the hilus of the dentate gyrus (CA4) (Fig. 6A, B), except for one case (C2, Table 1). In AD brains, 6 out of 10 cases showed moderate to abundant staining of DJ-1 (Table 1). DJ-1 immunoreactivity was observed in pyramidal neurons (cytoplasm and neuronal processes) of CA1–4 regions (Fig. 6C, D). Examination of other cortical areas revealed DJ-1 immunopositive neurons in the enthorinal cortex, frontal lobe and occipital lobe (data not shown). The staining for DJ-1 in brain sections from control and AD subjects was summarized in Table 1.


Increased DJ-1 expression under oxidative stress and in Alzheimer's disease brains.

Baulac S, Lu H, Strahle J, Yang T, Goldberg MS, Shen J, Schlossmacher MG, Lemere CA, Lu Q, Xia W - Mol Neurodegener (2009)

Enhanced immunostaining of DJ-1 in AD but not control brains. A, B. control brains (n = 9) showed weak or no DJ-1 staining in pyramidal neurons of the CA1, CA2, CA3 sub-regions and the hilus of the dentate gyrus (CA4). C, D. AD brains (n = 6/10) showed DJ-1 immunoreactivity in pyramidal neurons (cytoplasm and neuronal processes) of CA1–4 regions. Magnification: A, C = 4×; B, D = 40×.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2654450&req=5

Figure 6: Enhanced immunostaining of DJ-1 in AD but not control brains. A, B. control brains (n = 9) showed weak or no DJ-1 staining in pyramidal neurons of the CA1, CA2, CA3 sub-regions and the hilus of the dentate gyrus (CA4). C, D. AD brains (n = 6/10) showed DJ-1 immunoreactivity in pyramidal neurons (cytoplasm and neuronal processes) of CA1–4 regions. Magnification: A, C = 4×; B, D = 40×.
Mentions: Control brains (n = 9) also showed DJ-1 immunoreactivity in scattered astrocytes (data not shown), but they showed weak or no DJ-1 staining in pyramidal neurons of the CA1, CA2, CA3 sub-regions and the hilus of the dentate gyrus (CA4) (Fig. 6A, B), except for one case (C2, Table 1). In AD brains, 6 out of 10 cases showed moderate to abundant staining of DJ-1 (Table 1). DJ-1 immunoreactivity was observed in pyramidal neurons (cytoplasm and neuronal processes) of CA1–4 regions (Fig. 6C, D). Examination of other cortical areas revealed DJ-1 immunopositive neurons in the enthorinal cortex, frontal lobe and occipital lobe (data not shown). The staining for DJ-1 in brain sections from control and AD subjects was summarized in Table 1.

Bottom Line: We found that DJ-1 was expressed early during zebrafish development and throughout adulthood.While a slight reduction in staining for islet-1 positive neurons was observed in both DJ-1 KD and H2O2 treated embryos, the number of apoptotic cells was significantly increased in both KD and H2O2 treated embryos.Therefore, our results strongly suggest that DJ-1 expression is not necessary during zebrafish development but can be induced in zebrafish exposed to oxidative stress and is present in human AD brains.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Harvard University, Boston, MA 02115, USA. wxia@rics.bwh.harvard.edu.

ABSTRACT
Mutations in the DJ-1 gene have been linked to autosomal recessive familial Parkinson's disease. To understand the function of DJ-1, we determined the DJ-1 expression in both zebrafish and post mortem human brains. We found that DJ-1 was expressed early during zebrafish development and throughout adulthood. Knock down (KD) of DJ-1 by injection of morpholino did not cause dramatic morphologic alterations during development, and no loss of dopaminergic neurons was observed in embryos lacking DJ-1. However, DJ-1 KD embryos were more susceptible to programmed cell death. While a slight reduction in staining for islet-1 positive neurons was observed in both DJ-1 KD and H2O2 treated embryos, the number of apoptotic cells was significantly increased in both KD and H2O2 treated embryos. Interestingly, DJ-1 expression was increased in brains of zebrafish under conditions of oxidative stress, indicating that DJ-1 is a part of stress-responsive machinery. Since oxidative stress is one of the major contributors to the development of Alzheimer's disease (AD), we also examined DJ-1 expression in AD brains. Using DJ-1 specific antibodies, we failed to detect a robust staining of DJ-1 in brain tissues from control subjects. However, DJ-1 immunoreactivity was detected in hippocampal pyramidal neurons and astrocytes of AD brains. Therefore, our results strongly suggest that DJ-1 expression is not necessary during zebrafish development but can be induced in zebrafish exposed to oxidative stress and is present in human AD brains.

No MeSH data available.


Related in: MedlinePlus