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Molecular markers for granulovacuolar degeneration are present in rimmed vacuoles.

Nakamori M, Takahashi T, Nishikawa T, Yamazaki Y, Kurashige T, Maruyama H, Arihiro K, Matsumoto M - PLoS ONE (2013)

Bottom Line: We compared immunoreactivity and staining patterns for GVD markers.GVD markers, including lipid raft-associated proteins and tau kinases, were detected in RVs.These results suggest that RVs of muscle cells and GVD bodies of neurons share a number of molecules, such as raft-related proteins and tau-modifying proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.

ABSTRACT

Background: Rimmed vacuoles (RVs) are round-oval cytoplasmic inclusions, detected in muscle cells of patients with myopathies, such as inclusion body myositis (IBM) and distal myopathy with RVs (DMRV). Granulovacuolar degeneration (GVD) bodies are spherical vacuoles containing argentophilic and hematoxyphilic granules, and are one of the pathological hallmarks commonly found in hippocampal pyramidal neurons of patients with aging-related neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. These diseases are common in the elderly and share some pathological features. Therefore, we hypothesized that mechanisms of vacuolar formation in RVs and GVD bodies are common despite their role in two differing pathologies. We explored the components of RVs by immunohistochemistry, using antibodies for GVD markers.

Methods: Subjects included one AD case, eight cases of sporadic IBM, and three cases of DMRV. We compared immunoreactivity and staining patterns for GVD markers. These markers included: (1) tau-modifying proteins (caspase 3, cyclin-dependent kinase 5 [CDK5], casein kinase 1δ [CK1δ], and c-jun N-terminal kinase [JNK]), (2) lipid raft-associated materials (annexin 2, leucine-rich repeat kinase 2 [LRRK2], and flotillin-1), and (3) other markers (charged multi-vesicular body protein 2B [CHMP2B] and phosphorylated transactive response DNA binding protein-43 [pTDP43]) in both GVD bodies and RVs. Furthermore, we performed double staining of each GVD marker with pTDP43 to verify the co-localization.

Results: GVD markers, including lipid raft-associated proteins and tau kinases, were detected in RVs. CHMP2B, pTDP43, caspase 3, LRRK2, annexin 2 and flotillin-1 were detected on the rim and were diffusely distributed in the cytoplasm of RV-positive fibers. CDK5, CK1δ and JNK were detected only on the rim. In double staining experiments, all GVD markers colocalized with pTDP43 in RVs.

Conclusions: These results suggest that RVs of muscle cells and GVD bodies of neurons share a number of molecules, such as raft-related proteins and tau-modifying proteins.

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Related in: MedlinePlus

Immunohistochemistry for GVD markers in the Alzheimer's disease hippocampus.Anti-CHMP2B (A), anti-caspase3 (B), anti-cyclin-dependent kinase 5 (CDK5) (C), anti-casein kinase 1δ (CK1δ) (D), anti-c-jun N-terminal kinase (JNK) (E), anti-leucine-rich repeat kinase 2 (LRRK2) (F), anti-annexin2 (G), anti-flotillin-1 (H), and anti-phosphorylated transactive response DNA binding protein-43 (pTDP43) (I). Arrows indicate granulovacuolar degeneration (GVD) bodies. Scale bars  = 20 µm.
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pone-0080995-g003: Immunohistochemistry for GVD markers in the Alzheimer's disease hippocampus.Anti-CHMP2B (A), anti-caspase3 (B), anti-cyclin-dependent kinase 5 (CDK5) (C), anti-casein kinase 1δ (CK1δ) (D), anti-c-jun N-terminal kinase (JNK) (E), anti-leucine-rich repeat kinase 2 (LRRK2) (F), anti-annexin2 (G), anti-flotillin-1 (H), and anti-phosphorylated transactive response DNA binding protein-43 (pTDP43) (I). Arrows indicate granulovacuolar degeneration (GVD) bodies. Scale bars  = 20 µm.

Mentions: We next compared the immunoreactivity of RVs in the hippocampus of an AD case with those of muscle tissue, using antibodies against reported GVD markers (tau-modifying proteins, lipid raft-associated materials, CHMP2B and pTDP43). GVD bodies were immunopositive for all antibodies and mainly found in the CA1 subregion of the hippocampus (Fig. 3). In pyramidal cells, caspase 3, CDK5, JNK, annexin 2, LRRK2, flotillin-1 and pTDP43 were diffusely distributed in the cytoplasm, forming fine spherical granules, as well as GVD bodies (Fig. 3). NFTs were immunopositive for caspase 3, CDK5, LRRK2, annexin 2, flotillin-1 and pTDP43.


Molecular markers for granulovacuolar degeneration are present in rimmed vacuoles.

Nakamori M, Takahashi T, Nishikawa T, Yamazaki Y, Kurashige T, Maruyama H, Arihiro K, Matsumoto M - PLoS ONE (2013)

Immunohistochemistry for GVD markers in the Alzheimer's disease hippocampus.Anti-CHMP2B (A), anti-caspase3 (B), anti-cyclin-dependent kinase 5 (CDK5) (C), anti-casein kinase 1δ (CK1δ) (D), anti-c-jun N-terminal kinase (JNK) (E), anti-leucine-rich repeat kinase 2 (LRRK2) (F), anti-annexin2 (G), anti-flotillin-1 (H), and anti-phosphorylated transactive response DNA binding protein-43 (pTDP43) (I). Arrows indicate granulovacuolar degeneration (GVD) bodies. Scale bars  = 20 µm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842945&req=5

pone-0080995-g003: Immunohistochemistry for GVD markers in the Alzheimer's disease hippocampus.Anti-CHMP2B (A), anti-caspase3 (B), anti-cyclin-dependent kinase 5 (CDK5) (C), anti-casein kinase 1δ (CK1δ) (D), anti-c-jun N-terminal kinase (JNK) (E), anti-leucine-rich repeat kinase 2 (LRRK2) (F), anti-annexin2 (G), anti-flotillin-1 (H), and anti-phosphorylated transactive response DNA binding protein-43 (pTDP43) (I). Arrows indicate granulovacuolar degeneration (GVD) bodies. Scale bars  = 20 µm.
Mentions: We next compared the immunoreactivity of RVs in the hippocampus of an AD case with those of muscle tissue, using antibodies against reported GVD markers (tau-modifying proteins, lipid raft-associated materials, CHMP2B and pTDP43). GVD bodies were immunopositive for all antibodies and mainly found in the CA1 subregion of the hippocampus (Fig. 3). In pyramidal cells, caspase 3, CDK5, JNK, annexin 2, LRRK2, flotillin-1 and pTDP43 were diffusely distributed in the cytoplasm, forming fine spherical granules, as well as GVD bodies (Fig. 3). NFTs were immunopositive for caspase 3, CDK5, LRRK2, annexin 2, flotillin-1 and pTDP43.

Bottom Line: We compared immunoreactivity and staining patterns for GVD markers.GVD markers, including lipid raft-associated proteins and tau kinases, were detected in RVs.These results suggest that RVs of muscle cells and GVD bodies of neurons share a number of molecules, such as raft-related proteins and tau-modifying proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.

ABSTRACT

Background: Rimmed vacuoles (RVs) are round-oval cytoplasmic inclusions, detected in muscle cells of patients with myopathies, such as inclusion body myositis (IBM) and distal myopathy with RVs (DMRV). Granulovacuolar degeneration (GVD) bodies are spherical vacuoles containing argentophilic and hematoxyphilic granules, and are one of the pathological hallmarks commonly found in hippocampal pyramidal neurons of patients with aging-related neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. These diseases are common in the elderly and share some pathological features. Therefore, we hypothesized that mechanisms of vacuolar formation in RVs and GVD bodies are common despite their role in two differing pathologies. We explored the components of RVs by immunohistochemistry, using antibodies for GVD markers.

Methods: Subjects included one AD case, eight cases of sporadic IBM, and three cases of DMRV. We compared immunoreactivity and staining patterns for GVD markers. These markers included: (1) tau-modifying proteins (caspase 3, cyclin-dependent kinase 5 [CDK5], casein kinase 1δ [CK1δ], and c-jun N-terminal kinase [JNK]), (2) lipid raft-associated materials (annexin 2, leucine-rich repeat kinase 2 [LRRK2], and flotillin-1), and (3) other markers (charged multi-vesicular body protein 2B [CHMP2B] and phosphorylated transactive response DNA binding protein-43 [pTDP43]) in both GVD bodies and RVs. Furthermore, we performed double staining of each GVD marker with pTDP43 to verify the co-localization.

Results: GVD markers, including lipid raft-associated proteins and tau kinases, were detected in RVs. CHMP2B, pTDP43, caspase 3, LRRK2, annexin 2 and flotillin-1 were detected on the rim and were diffusely distributed in the cytoplasm of RV-positive fibers. CDK5, CK1δ and JNK were detected only on the rim. In double staining experiments, all GVD markers colocalized with pTDP43 in RVs.

Conclusions: These results suggest that RVs of muscle cells and GVD bodies of neurons share a number of molecules, such as raft-related proteins and tau-modifying proteins.

Show MeSH
Related in: MedlinePlus