Fine structure of the Pick and Hirano bodies in a case of Pick's disease

Ss, Schochet; Pw, Lampert; Lindenberg, Richard

doi:10.1007/bf00686729

Cited by 101 publications

(26 citation statements)

References 9 publications

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“…4 and 5). The Hirano bodies induced by the expression of the 34-kDa ⌬EF1 protein are similar to the Hirano bodies seen in autopsy samples of brain tissue on the basis of the following criteria: (i) the Hirano bodies are enriched for actin and actin binding proteins (19,22,25,27,39,61); (ii) the structures are highly ordered and present elliptical cross-sections that are rod or disk shaped, depending on the overall length (24,25); (iii) the appearance varies with the plane of section or tilt of the stage due to the paracrystalline order of the structure (62,69); (iv) the inclusions frequently reveal juxtaposition of ordered and disordered regions (53,62); and (v) the structures contain strata of intersecting or interwoven parallel filament arrays (62). Hirano bodies are distinct from actin-cofilin rods, which are needlelike structures composed of a single large bundle of longitudinally oriented actin filaments that can form either in the nucleus or in the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

“…During the past three decades, Hirano bodies have been reported to be associated with a broad array of conditions, including Alzheimer's disease (21,44,45,60), Parkinson's disease (25), Pick's disease (61), amyotrophic lateral sclerosis (25), ataxic Creutzfeldt-Jakob disease (3), kuru (9), scrapie (10), leukoencephalopathy (23), chronic alcoholism (32), diabetes (64), cancer (12,20), muscle degeneration (11), and neuronal degeneration associated with abnormal copper homeostasis (1,46,53,71). Hirano bodies are paracrystalline cytoplasmic inclusions that contain actin filaments and actinassociated proteins (19,22,39).…”

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Formation of Hirano Bodies Induced by Expression of an Actin Cross-Linking Protein with a Gain-of-Function Mutation

et al. 2003

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Hirano bodies are paracrystalline actin filament-containing structures reported to be associated with a variety of neurodegenerative diseases. However, the biological function of Hirano bodies remains poorly understood, since nearly all prior studies of these structures were done with postmortem samples of tissue. In the present study, we generated a full-length form of a Dictyostelium 34-kDa actin cross-linking protein with point mutations in the first putative EF hand, termed 34-kDa ⌬EF1. The 34-kDa ⌬EF1 protein binds calcium normally but has activated actin binding that is unregulated by calcium. The expression of the 34-kDa ⌬EF1 protein in Dictyostelium induces the formation of Hirano bodies, as assessed by both fluorescence microscopy and transmission electron microscopy. Dictyostelium cells bearing Hirano bodies grow normally, indicating that Hirano bodies are not associated with cell death and are not deleterious to cell growth. Moreover, the expression of the 34-kDa ⌬EF1 protein rescues the phenotypes of cells lacking the 34-kDa protein and cells lacking both the 34-kDa protein and ␣-actinin. Finally, the expression of the 34-kDa ⌬EF1 protein also initiates the formation of Hirano bodies in cultured mouse fibroblasts. These results show that the failure to regulate the activity and/or affinity of an actin cross-linking protein can provide a signal for the formation of Hirano bodies. More generally, the formation of Hirano bodies is a cellular response to or a consequence of aberrant function of the actin cytoskeleton.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Formation of Hirano Bodies Induced by Expression of an Actin Cross-Linking Protein with a Gain-of-Function Mutation

et al. 2003

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“…There are several characterized actin inclusions found in human disease such as ADF/cofilin rods (AC rods) and hyaline bodies [44][45][46]. Hirano bodies are differentiated from these other actin aggregates by their eosinophilic nature, ability to bind to phalloidin, and distinctive ultrastructure [47,8,7,45]. To definitively prove an actin inclusion is a Hirano body, electron microscopy must be performed for ultrastructural analysis.…”

Section: Incidence and Ultrastructure Of Hirano Bodies In Transgenic mentioning

confidence: 99%

Hirano body expression impairs spatial working memory in a novel mouse model

Furgerson

Clark

Crystal

et al. 2014

Acta Neuropathologica Communications

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Introduction: Hirano bodies are actin-rich intracellular inclusions found in the brains of patients with neurodegenerative conditions such as Alzheimer's disease or frontotemporal lobar degeneration-tau. While Hirano body ultrastructure and protein composition have been well studied, little is known about the physiological function of Hirano bodies in an animal model system. Results: Utilizing a Cre/Lox system, we have generated a new mouse model which develops an age-dependent increase in the number of model Hirano bodies present in both the CA1 region of the hippocampus and frontal cortex. These mice develop normally and experience no overt neuron loss. Mice presenting model Hirano bodies have no abnormal anxiety or locomotor activity as measured by the open field test. However, mice with model Hirano bodies develop age-dependent impairments in spatial working memory performance assessed using a delayed win-shift task in an 8-arm radial maze. Synaptic transmission, short-term plasticity, and long-term plasticity was measured in the CA1 region from slices obtained from both the ventral and dorsal hippocampus in the same mice whose spatial working memory was assessed. Baseline synaptic responses, paired pulse stimulation and long-term potentiation measurements in the ventral hippocampus were indistinguishable from control mice. In contrast, in the dorsal hippocampus, synaptic transmission at higher stimulus intensities were suppressed in 3 month old mice with Hirano bodies as compared with control mice. In addition, long-term potentiation was enhanced in the dorsal hippocampus of 8 month old mice with Hirano bodies, concurrent with observed impairment of spatial working memory. Finally, an inflammatory response was observed at 8 months of age in mice with Hirano bodies as assessed by the presence of reactive astrocytes. Conclusion: This study shows that the presence of model Hirano bodies initiates an inflammatory response, alters hippocampal synaptic responses, and impairs spatial working memory in an age-dependent manner. This suggests that Hirano bodies may promote disease progression. This new model mouse provides a tool to investigate how Hirano bodies interact with other pathologies associated with Alzheimer's disease. Hirano bodies likely play a complex and region specific role in the brain during neurodegenerative disease progression.

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“…Hirano bodies are large, eosinophilic, actin-rich intracytoplasmic structures that contain paracrystalline arrays of F-actin (6) and actin-binding proteins (7). Hirano bodies have been described in postmortem tissues and are found primarily in the CA1 area of Ammon's horn of the hippocampus (8)(9)(10). Hirano bodies have been found to be associated with a number of different neurodegenerative diseases, such as Alzheimer's disease (11-13), Pick's disease (9,14), and Guam amylotrophic lateral sclerosis and parkinsonism-dementia complex (8).…”

mentioning

confidence: 99%

“…Hirano bodies have been described in postmortem tissues and are found primarily in the CA1 area of Ammon's horn of the hippocampus (8)(9)(10). Hirano bodies have been found to be associated with a number of different neurodegenerative diseases, such as Alzheimer's disease (11-13), Pick's disease (9,14), and Guam amylotrophic lateral sclerosis and parkinsonism-dementia complex (8). Hirano bodies have also been associated with chronic alcoholism (15), as well as general aging (5).…”

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confidence: 99%