Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012:2012:271732.
doi: 10.1155/2012/271732. Epub 2012 Mar 25.

Neuroinflammation in Parkinson's Disease and Related Disorders: A Lesson from Genetically Manipulated Mouse Models of α-Synucleinopathies

Kazunari Sekiyama  1 , Shuei Sugama, Masayo Fujita, Akio Sekigawa, Yoshiki Takamatsu, Masaaki Waragai, Takato Takenouchi, Makoto Hashimoto
Affiliations

Neuroinflammation in Parkinson's Disease and Related Disorders: A Lesson from Genetically Manipulated Mouse Models of α-Synucleinopathies

Kazunari Sekiyama et al. Parkinsons Dis. 2012.

Abstract

Neuroinflammation in Parkinson's disease (PD) is a chronic process that is associated with alteration of glial cells, including astrocytes and microglia. However, the precise mechanisms remain obscure. To better understand neuroinflammation in PD, we focused on glial activation in α-synuclein (αS) transgenic and related model mice. In the majority of αS transgenic mice, astrogliosis was observed concomitantly with accumulation of αS during the early stage of neurodegeneration. However, microglia were not extensively activated unless the mice were treated with lipopolysaccharides or through further genetic modification of other molecules, including familial PD risk factors. Thus, the results in αS transgenic mice and related model mice are consistent with the idea that neuroinflammation in PD is a double-edged sword that is protective in the early stage of neurodegeneration but becomes detrimental with disease progression.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Characterization of glial activation in a P123HβS tg mouse and an αS/P123HβS bigenic mouse.(a) Concomitant with P123HβS-positive dot-like axonal accumulation (upper), GFAP-positive reactive astrocytes were observed in the hippocampus of a P123HβS tg mouse, but not in a wild-type mouse (lower). Scale bar = 20 μm. (b) Immunostaining with anti-CD11b antibody showed microglial activation in an αS/P123HβS bigenic mouse, but not in a wild-type mouse. Scale bar = 20 μm. The figures in (a) and (b) were reprinted from Fujita et al., [28], with permission, or are unpublished data related to the same paper.
Figure 2
Figure 2
Schematic hypothesis of glial activations in the αS tg mouse. Astrocytes may quickly respond to αS released from degenerating neurons to protect against neurodegeneration. During the long time course of neurodegeneration, these activated astrocytes may lose their protective properties or might be aberrantly activated, leading to stimulation of neuroinflammation. This process may be stimulated by loss of function of DJ-1. In contrast, microglia may be protective during the early stage of neurodegeneration and are not readily activated unless they are stimulated with LPS or with alterations of other familial PD risk factors such as Parkin, PINK1, LRRK2, and other members of the synuclein family of peptides, including mutant βS.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hashimoto M, Masliah E. α-Synuclein in Lewy body disease and Alzheimer’s disease. Brain Pathology. 1999;9(4):707–720. - PMC - PubMed
    1. Trojanowski JQ, Goedert M, Iwatsubo T, Lee VMY. Fatal attractions: abnormal protein aggregation and neuron death in Parkinson’s disease and Lewy body dementia. Cell Death and Differentiation. 1998;5(10):832–837. - PubMed
    1. Rochet JC, Lansbury PT., Jr. Amyloid fibrillogenesis: themes and variations. Current Opinion in Structural Biology. 2000;10(1):60–68. - PubMed
    1. Beyer K, Domingo-Sabat M, Ariza A. Molecular pathology of lewy body diseases. International Journal of Molecular Sciences. 2009;10(3):724–745. - PMC - PubMed
    1. Block ML, Zecca L, Hong JS. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nature Reviews Neuroscience. 2007;8(1):57–69. - PubMed

LinkOut - more resources