Brain Pathology
1015-6305
1750-3639
Mỹ
Cơ quản chủ quản: Wiley-Blackwell , WILEY
Lĩnh vực:
Pathology and Forensic MedicineNeurology (clinical)Neuroscience (miscellaneous)
Phân tích ảnh hưởng
Thông tin về tạp chí
Brain Pathology is the journal of choice for biomedical scientists investigating diseases of the nervous system. The official journal of the International Society of Neuropathology, Brain Pathology is a peer-reviewed quarterly publication that includes original research, review articles and symposia focuses on the pathogenesis of neurological disease.
Các bài báo tiêu biểu
Presence of Tissue Transglutaminase in Granular Endoplasmic Reticulum is Characteristic of Melanized Neurons in Parkinson's Disease Brain Abstract Parkinson's disease (PD) is characterized by the accumulation of α‐synuclein aggregates and degeneration of melanized neurons. The tissue transglutaminase (tTG) enzyme catalyzes molecular protein cross‐linking. In PD brain, tTG‐induced cross‐links have been identified in α‐synuclein monomers, oligomers and α‐synuclein aggregates. However, whether tTG and α‐synuclein occur together in PD affected neurons remains to be established. Interestingly, using immunohistochemistry, we observed a granular distribution pattern of tTG, characteristic of melanized neurons in PD brain. Apart from tTG, these granules were also positive for typical endoplasmic reticulum (ER)‐resident chaperones, that is, protein disulphide isomerase, ERp57 and calreticulin, suggesting a direct link to the ER. Additionally, we observed the presence of phosphorylated pancreatic ER kinase (pPERK), a classical ER stress marker, in tTG granule positive neurons in PD brain, although no subcellular colocalization of tTG and pPERK was found. Our data therefore suggest that tTG localization to granular ER compartments is specific for stressed melanized neurons in PD brain. Moreover, as also α‐synuclein aggregates were observed in tTG granule positive neurons, these results provide a clue to the cellular site of interaction between α‐synuclein and tTG.
Tập 21 Số 2 - Trang 130-139 - 2011
Ubiquitin in Neurodegenerative Diseases Immunochemical staining to detect ubiquitin has become an essential technique in evaluating neurodegenerative processes. Age related staining is seen in myelin, in nerve processes in lysosome‐related dense bodies, and in corpora amylacea. There is a constant association between filamentous inclusions and the presence of ubiquitin. Intermediate filaments associated with ubiquitin, α B crystallin and enzymes of the ubiquitin pathway are the basis of Lewy bodies and Rosenthal fibres, as well as related bodies outside the nervous system. Neurofibrillary tangles in diverse diseases are associated with ubiquitin as are several other tau containing inclusions in both neurones and glia. Inclusions in motor neurones and non‐motor cortex characterizing amyotrophic lateral sclerosis (ALS) and certain related forms of frontal lobe dementia can only be readily detected by anti‐ubiquitin. Anti‐ubiquitin also identifies both filamentous and lysosomal structures in neuronal processes as well as in some swollen neurones. Involvement of ubiquitin‐containing elements of the lysosomal system appears important in pathogenesis of prion encephalopathies. Despite great advances in understanding cell biology of the ubiquitin pathway there are as yet few insights into the precise role played by ubiquitin in neuronal disease.
Tập 3 Số 1 - Trang 55-65 - 1993
Activity‐Regulated Cytoskeleton‐Associated Protein in Rodent Brain is Down‐Regulated by High Fat Diet <i>in vivo</i> and by 27‐Hydroxycholesterol <i>in vitro</i> Abstract Growing evidence strongly suggests that high fat diet (HFD) has an important role in some neurodegenerative disorders, including Alzheimer's disease (AD). To identify new cellular pathways linking hypercholesterolemia and neurodegeneration, we analyzed the effects of HFD on gene expression in mouse brain. Using cDNA microarrays and real time RT‐PCR, we found that HFD has a mild, but significant effect on the expression of several genes. The altered genes include molecules linked to AD pathology and others of potential interest for neurodegeneration. We further investigated the effect of HFD on the activity‐regulated cytoskeleton‐associated protein (Arc). Expression of Arc was decreased in cerebral cortex and hippocampus of HFD‐fed animals. From the known regulatory mechanisms of Arc expression, HFD reduced N‐methyl‐D‐aspartate receptor (NMDAR) activity, as seen by decreases in tyrosine phosphorylation of NMDAR2A and levels of NMDAR1. Additionally, we demonstrated that 27‐hydroxycholesterol, a cholesterol metabolite that enters the brain from the blood, decreases Arc levels as well as NMDAR and Src kinase activities in rat primary hippocampal neurons. Finally, we showed that Arc levels are decreased in the cortex of AD brains. We propose that one of the mechanisms, by which hypercholesterolemia contributes to neurodegenerative diseases, could be through Arc down‐regulation caused by 27‐hydroxycholesterol.
Tập 19 Số 1 - Trang 69-80 - 2009
Bovine Spongiform Encephalopathy: A Neuropathological Perspective The occurrence of bovine spongiform encephalopathy (BSE), recognition that it is a new scrapie‐like disease epidemic in domestic cattle in the United Kingdom and concern of a remote zoonotic potential has, in four years, produced a plethora of documented information. While much of this information has been communicated outwith the scientific literature, this review attempts to summarise, from a neuropathological viewpoint, the main findings to emerge. The initial studies established the nosological homology of BSE with the subacute spongiform encephalopathies or “prion” diseases of animals and man. Epidemiological data are consistent with an extended common source epidemic originating from an abrupt change, commencing in 1981‐82, in the exposure of domestic cattle to a scrapie‐like agent in meat and bone meal incorporated into commercial animal feedstuffs. It is currently proposed that the method of production of meat and bone meal has contributed vital factors to the change in exposure. Invariability of the distribution pattern of vacuolar pathology in the natural disease and on primary transmission to cattle suggests a uniformity of the pathogenesis of BSE. Studies in mice suggest uniformity also of the biological properties of different BSE isolates but indicate that the properties differ from those of sheep scrapie isolates. Human health risks, although perceived to be negligible, have been addressed by various strategies including statutory measures and long term monitoring.
Tập 1 Số 2 - Trang 69-78 - 1991
Role of Microglia in Neuronal Cell Death in Prion Disease To elucidate the role played by the prion protein in scrapie pathogenesis, we performed experiments with PrP27–30 isolated from scrapie‐infected hamster brains in cell culture and studied in vivo the temporal and spatial correlation between deposition of the disease‐associated isoform of the prion protein (PrPSc ), microglial activation and neuronal cell death in mice infected with scrapie strains 79A, ME7 and RML. The results presented here show that cellular expression of PrPc and the presence of microglia are necessary for the neurotoxicity of PrPSc in vitro. In vivo , accumulation of protease‐resistant prion protein was detected early in the incubation period using the histoblot technique. Microglial activation was also detected early in the incubation period of all models studied. Both the time course and the spatial distribution of microglial activation closely resembled the pattern of PrPSc deposition. Microglial activation clearly preceded the detection of apoptotic neuronal cell death which was assessed using the in situ end‐labeling technique (ISEL). Taken together, our results indicate that microglial activation is involved in the neurotoxicity of PrPSc both in vitro and in vivo.
Tập 8 Số 3 - Trang 449-457 - 1998
Neuronal Apoptosis in Fatal Familial Insomnia The possibility that neuronal loss in prion diseases occurs through an apoptotic process has been postulated and is consistent with the lack of inflammation in these disorders. In order to test this hypothesis in FFI, in which neuronal loss is the predominant neuropathological feature, we examined samples of thalamus, basal ganglia, cerebral cortex, cerebellum and medulla from 10 subjects with FFI. All the patients had the characteristic 178 N mutation of the PrP gene. Eight subjects were homozygous methionine/methionine at codon 129 and 2 were heterozygous methionine/valine. Apoptotic neurons were identified by in situ end labelling in all the FFI cases and in none of the controls. They were mostly found in damaged regions and their presence and abundance seemed to correlate closely with the neuronal loss. They were particularly abundant in the thalamus and medullary olives. In heterozygous cases who had a longer disease duration and more widespread cerebral changes, apoptotic neurons were also found in the neocortex and striatum. The abundance of apoptotic neurons also correlated well with microglial activation as demonstrated by the expression of major histocompatibility complex class II antigens. PrPres immunostaining was almost invariably negative, consistent with previous data showing the lack of obvious correlation between neuronal loss and PrPres deposits in prion diseases.
Tập 8 Số 3 - Trang 531-537 - 1998
Clinicopathological Correlations in Pituitary Adenomas Abstract Pituitary adenomas are common neuroendocrine neoplasms arising from adenohypophysial cells. Recent progress in our understanding of pituitary tumorigenesis as well as pathways involved in molecular cytodifferentiation of the adenohypophysis has impacted on the classification of pituitary adenomas. The detailed comprehensive classification of pituitary adenomas is now well recognized to reflect specific clinical features and genetic changes that predict targeted treatments, as well as prognostic information for patients with pituitary adenomas. Therefore, the clinical responsibility of pathologists is not only limited to the distinction of pituitary adenomas from other sellar lesions, but also to provide a comprehensive subtype classification using appropriate ancillary tools. In this article, we highlight an approach to clinical diagnosis and pitfalls in the classification of these common neoplasms.
Tập 22 Số 4 - Trang 443-453 - 2012
Detection of Ectopic B‐cell Follicles with Germinal Centers in the Meninges of Patients with Secondary Progressive Multiple Sclerosis Multiple sclerosis (MS) is characterized by synthesis of oligoclonal immunoglobulins and the presence of B‐cell clonal expansions in the central nervous system (CNS). Because ectopic lymphoid tissue generated at sites of chronic inflammation is thought to be important in sustaining immunopathological processes, we have investigated whether structures resembling lymphoid follicles could be identified in the CNS of MS patients. Sections from post‐mortem MS brains and spinal cords were screened using immunohistochemistry for the presence of CD20+ B‐cells, CD3+ T‐cells, CD 138+ plasma cells and CD21+ , CD35+ follicular dendritic cells, and for the expression of lymphoid chemokines (CXCL13, CCL21) and peripheral node addressin (PNAd). Lymphoid follicle‐like structures containing B‐cells, T‐cells and plasma cells, and a network of follicular dendritic cells producing CXCL13 were observed in the cerebral meninges of 2 out of 3 patients with secondary progressive MS, but not in relapsing remitting and primary progressive MS. We also show that proliferating B‐cells are present in intrameningeal follicles, a finding which is suggestive of germinal center formation. No follicle‐like structures were detected in parenchymal lesions. The formation of ectopic lymphoid follicles in the meninges of patients with MS could represent a critical step in maintaining humoral autoimmunity and in disease exacerbation.
Tập 14 Số 2 - Trang 164-174 - 2004
Genetically Engineered Mouse Models of Brain Cancer and the Promise of Preclinical Testing Abstract Recent improvements in the understanding of brain tumor biology have opened the door to a number of rational therapeutic strategies targeting distinct oncogenic pathways. The successful translation of such “designer drugs” to clinical application depends heavily on effective and expeditious screening methods in relevant disease models. By recapitulating both the underlying genetics and the characteristic tumor‐stroma microenvironment of brain cancer, genetically engineered mouse models (GEMMs) may offer distinct advantages over cell culture and xenograft systems in the preclinical testing of promising therapies. This review focuses on recently developed GEMMs for both glioma and medulloblastoma, and discusses their potential use in preclinical trials. Examples showcasing the use of GEMMs in the testing of molecularly targeted therapeutics are given, and relevant topics, such as stem cell biology, in vivo imaging technology and radiotherapy, are also addressed.
Tập 19 Số 1 - Trang 132-143 - 2009
Charcot‐Marie‐Tooth Neuropathy Type 2 and P0 Point Mutations: Two Novel Amino Acid Substitutions (Asp61Gly; Tyr119Cys) and a Possible “Hotspot” on Thr124Met Mutations in the gene for the major protein component of peripheral nerve myelin, myelin protein zero (MPZ, P0), cause hereditary disorders of Schwann cell myelin such as Charcot‐Marie‐Tooth neuropathy type 1B (CMT1B), Dejerine‐Sottas syndrome (DSS), and congenital hypomyelinating neu‐ropathy (CHN). More recently, P0 mutations were identified in the axonal type of CMT neuropathy, CMT2, which is different from the demyelinating variants with respect to electroneurography and nerve pathology. We screened 49 patients with a clinical and histopathological diagnosis of CMT2 for mutations in the P0 gene. Three heterozygous single nucleotide changes were detected: two novel mis‐sense mutations, Asp61Gly and Tyr119Cys, and the known Thr124Met substitution, that has already been reported in several CMT patients from different European countries. Haplotype analysis for the P0 locus proved that our patients with the 124Met allele were not related to a cohort of patients with the same mutation, all of Belgian descent and all found to share a common ancestor (7).Our data suggest that P0 mutations account for a detectable proportion of CMT2 cases with virtually every patient harbouring a different mutation but recurrence of the Thr124Met amino acid substitution.The high frequency of this peculiar genotype in the European CMT population is presumably not only due to a founder effect but Thr124Met might constitute a mutation hotspot in the P0 gene as well.
Tập 10 Số 2 - Trang 235-248 - 2000