Abstract:
AIMS:Oxidative damage and an associated DNA damage response (DDR) are evident in mild cognitive impairment and early Alzheimer's disease, suggesting that neuronal dysfunction resulting from oxidative DNA damage may account for some of the cognitive impairment not fully explained by Alzheimer-type pathology. METHODS:Frontal cortex (Braak stage 0-II) was obtained from the Medical Research Council's Cognitive Function and Ageing Study cohort. Neurones were isolated from eight cases (four high and four low DDR) by laser capture microdissection and changes in the transcriptome identified by microarray analysis. RESULTS:Two thousand three hundred seventy-eight genes were significantly differentially expressed (1690 up-regulated, 688 down-regulated, P < 0.001) in cases with a high neuronal DDR. Functional grouping identified dysregulation of cholesterol biosynthesis, insulin and Wnt signalling, and up-regulation of glycogen synthase kinase 3β. Candidate genes were validated by quantitative real-time polymerase chain reaction. Cerebrospinal fluid levels of 24(S)-hydroxycholesterol associated with neuronal DDR across all Braak stages (rs = 0.30, P = 0.03). CONCLUSIONS:A persistent neuronal DDR may result in increased cholesterol biosynthesis, impaired insulin and Wnt signalling, and increased GSK3β, thereby contributing to neuronal dysfunction independent of Alzheimer-type pathology in the ageing brain.
journal_name
Neuropathol Appl Neurobioljournal_title
Neuropathology and applied neurobiologyauthors
Simpson JE,Ince PG,Minett T,Matthews FE,Heath PR,Shaw PJ,Goodall E,Garwood CJ,Ratcliffe LE,Brayne C,Rattray M,Wharton SB,MRC Cognitive Function and Ageing Neuropathology Study Group.doi
10.1111/nan.12252subject
Has Abstractpub_date
2016-02-01 00:00:00pages
167-79issue
2eissn
0305-1846issn
1365-2990journal_volume
42pub_type
杂志文章abstract::Ten minutes of total cerebral ischaemia was produced in normo- and hypoglycaemic rats. The most conspicuous findings were loss of hippocampal (CA-1) pyramidal cells and Purkinje cells, which were most pronounced in the normoglycaemic rats. While pre-ischaemic hypoglycaemia to some extent protected these cells, it led ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1981.tb00091.x
更新日期:1981-05-01 00:00:00
abstract::Immunohistochemistry using antibodies to dystrophin is the pathological basis for the diagnosis of Duchenne and Becker muscular dystrophy (DMD and BMD). While the sarcolemma of DMD muscle is negative, BMD muscle generally shows variable labelling because of the translation of a partially functional dystrophin that is ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2004.00561.x
更新日期:2004-10-01 00:00:00
abstract::Over the last decade, there has been increasing evidence that hyperactivation of the mechanistic target of rapamycin (mTOR) pathway is a hallmark of malformations of cortical development such as focal cortical dysplasia (FCD) or hemimegalencephaly. The mTOR pathway governs protein and lipid synthesis, cell growth and ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/nan.12463
更新日期:2018-02-01 00:00:00
abstract:AIMS:Infection of the mouse central nervous system with wild type (WT) and vaccine strains of measles virus (MV) results in lack of clinical signs and limited antigen detection. It is considered that cell entry receptors for these viruses are not present on murine neural cells and infection is restricted at cell entry....
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2009.01023.x
更新日期:2009-10-01 00:00:00
abstract::A detailed investigation of the neuropathology of a horse affected with stringhalt was performed. Qualitative and quantitative light and electron microscopy, and single teased fibre preparations of peripheral nerve demonstrated predominantly axonal degeneration, the stage of which was appropriate for the duration of c...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1986.tb00054.x
更新日期:1986-09-01 00:00:00
abstract:AIMS:The serotonin 2A receptor (HTR2A) is widely expressed in the brain and involved in the modulation of fear, mood, anxiety and other symptoms. HTR2A and HTR2A gene variations are implicated in depression, schizophrenia, anxiety and obsessive-compulsive disorder. To understand HTR2A signalling changes in psychiatric ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12167
更新日期:2015-06-01 00:00:00
abstract::Cell death in gliomas may occur either by apoptosis, or, in the case of high grade tumours, by necrosis, but questions remain as to the pathogenesis and relationship between these processes. The development of cell death was investigated in multicellular glioma spheroid cultures. Spheroids model the development of cel...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.0305-1846.2001.00319.x
更新日期:2001-08-01 00:00:00
abstract:AIMS:Microglial cells have been originally identified as a target for the CXC chemokine, SDF-1, by their expression of CXCR4. More recently, it has been recognized that SDF-1 additionally binds to CXCR7, which depending on the cell type acts as either a nonclassical, a classical or a scavenger chemokine receptor. Here,...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12015
更新日期:2013-10-01 00:00:00
abstract:BACKGROUND:In definite Creutzfeldt-Jakob disease (CJD), morphological and immunohistochemical patterns are useful to identify molecular subtypes. Severe cerebellar pathology and hippocampal involvement helps to identify VV subtypes. The rare VV1 variant (<1%), more frequent in young individuals, is additionally charact...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2011.01208.x
更新日期:2012-04-01 00:00:00
abstract::Pathologists have been establishing archives of human organs and tissue for research use for many years now. Controversy has arisen recently over these collections, particularly with regard to the right of patients or relatives to consent to removal and retention of tissue, genetic research using stored tissue samples...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2990.2000.00276.x
更新日期:2000-10-01 00:00:00
abstract:AIMS:Alzheimer's disease (AD) is characterized by degeneration of cholinergic basal forebrain (CBF) neurons in the nucleus basalis of Meynert (nbM), which provides the major cholinergic input to the cortical mantle and is related to cognitive decline in patients with AD. Cortical histone deacetylase (HDAC) dysregulatio...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12518
更新日期:2019-06-01 00:00:00
abstract::Ultrastructural studies of spongiform encephalopathy (SE) reveal no very early pathological changes in kuru where membrane lamellation has been reported. This observation is challenged. In the later stages of SE, two main theories are examined--the spiroplasma theory and the prion (6 nm filament) theory. Neither are s...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1986.tb00047.x
更新日期:1986-03-01 00:00:00
abstract:AIMS:Frontotemporal lobar degeneration (FTLD) is clinically and pathologically heterogeneous. Although associated with variations in MAPT, GRN and C9ORF72, the pathogenesis of these, and of other nongenetic, forms of FTLD, remains unknown. Epigenetic factors such as histone regulation by histone deacetylases (HDAC) may...
journal_title:Neuropathology and applied neurobiology
pub_type: 历史文章,杂志文章
doi:10.1111/nan.12153
更新日期:2015-02-01 00:00:00
abstract:AIMS:post-haemorrhagic ventricular dilatation (PHVD) is a significant problem in neonatal care, with sequelae extending beyond childhood. Its management is important in determining outcome. Although rodent hydrocephalus models have been developed, PHVD, as a specific entity with a distinct pathophysiology, has not been...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2010.01118.x
更新日期:2011-02-01 00:00:00
abstract::This paper continues the historical review on the concept of a sensorimotor cortex into the twentieth century. Paul Flechsig was probably the first to accept this concept after the turn of the century. Like Munk, he believed in an almost reflex-like unity between cortical sensory and motor function. With the help of h...
journal_title:Neuropathology and applied neurobiology
pub_type: 历史文章,杂志文章
doi:10.1111/j.1365-2990.1982.tb00264.x
更新日期:1982-03-01 00:00:00
abstract::Damage to the frontal cortex and to the hippocampus, both in terms of cell loss and neuronal dysfunction, is thought to underlie many of the neurological and behavioural consequences of traumatic brain injury (TBI). Several studies have indicated that the hippocampus is particularly susceptible to central nervous syst...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.2003.00439.x
更新日期:2003-04-01 00:00:00
abstract:AIMS:Paediatric low-grade gliomas (pLGGs) are a heterogeneous group of brain tumours associated with a high overall survival: however, they are prone to recur and supratentorial lesions are difficult to resect, being associated with high percentage of disease recurrence. Our aim was to shed light on the biology of pLGG...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12479
更新日期:2018-12-01 00:00:00
abstract:AIMS:Plectin, a universally expressed multi-functional cytolinker protein, is crucial for intermediate filament networking, including crosstalk with actomyosin and microtubules. In addition to its involvement in a number of diseases affecting skin, skeletal muscle, heart, and other stress-exposed tissues, indications f...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12635
更新日期:2021-02-01 00:00:00
abstract::To confirm the intracellular accumulation of amyloid beta-protein (Abeta), we carefully performed immunohistochemistry using brains of cynomolgus monkeys of various ages. Cortical neurones and their large neurites were immunostained with antibodies against Abeta in young monkey brains. In aged monkey brains, intracell...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2004.00624.x
更新日期:2005-04-01 00:00:00
abstract::Herpes simplex virus was injected into the vitreous of suckling and adult rabbits. In the suckling rabbits the infection caused an arrested myelination of the strip. Further, the infected strips showed degenerative changes with splitting and distension of myelin sheaths which then disintegrated. Ultrastructurally, her...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1978.tb00530.x
更新日期:1978-01-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of upper and lower motor neurones leading to muscle weakness and paralysis. Despite recent advances in the genetics of ALS, the mechanisms underlying motor neurone degeneration are not fully understood. Mitochondria are know...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2990.2011.01166.x
更新日期:2011-06-01 00:00:00
abstract::Over the past few years, the traditional view of brain tumorigenesis has been revolutionized by advances in genomic medicine, molecular biology, stem cell biology and genetically engineered small-animal modelling. We now appreciate that paediatric brain tumours arise following specific genetic mutations in specialized...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2990.2011.01230.x
更新日期:2012-06-01 00:00:00
abstract::We have examined the influence that axons may have on the expression of proteolipid protein (PLP), the major myelin protein of the CNS. Partial transections were made of the optic nerve of adult rats to produce approximately a 50% loss of axons. Twenty-eight days after lesioning, sections of the distal nerves were imm...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1991.tb00725.x
更新日期:1991-08-01 00:00:00
abstract::CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a type of small-artery stroke and vascular dementia-inducing pathology of the brain. In order to explain the molecular mechanisms behind the alterations to the blood vessels in CADASIL subjects, we scrutinized the e...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.2003.00478.x
更新日期:2003-08-01 00:00:00
abstract::The aims of this experimental scanning electron microscopic study were to identify the levels at which cervical ventral nerve roots, or the rootlets by which they are attached to the spinal cord, rupture under traction and to document the resulting damage. This information would provide the basis of a rationale for re...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1989.tb01254.x
更新日期:1989-11-01 00:00:00
abstract::Mutations in the tau gene cause familial frontotemporal dementia with parkinsonism linked to chromosome 17 characterized by filamentous tau protein deposits. Here we describe the clinical and neuropathological features of a case from a newly identified family with an intron 10+3-splice site mutation in the tau gene. T...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2005.00629.x
更新日期:2005-08-01 00:00:00
abstract::Mitochondrial abnormalities, in particular the accumulation of mitochondrial DNA mutations, have been proposed as a potential cause of normal ageing. One group of patients with mtDNA disorders have a nuclear DNA defect which accelerates the chronological accumulation of mitochondrial DNA mutations. These patients prov...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.2001.00315.x
更新日期:2001-06-01 00:00:00
abstract:AIMS:Secreted protein, acidic and rich in cysteine (SPARC) is a regulator of cell-matrix interaction and has been associated with tumour stage and patient survival in various malignancies. As no large-scale study has yet been undertaken, we investigated human brain and astrocytomas for SPARC expression and associations...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2010.01072.x
更新日期:2010-04-01 00:00:00
abstract:AIMS:We observed a microvascular structure in the cerebral cortex that has not, to our knowledge, been previously described. We have termed the structure a 'raspberry', referring to its appearance under a bright-field microscope. We hypothesized that raspberries form through angiogenesis due to some form of brain ischa...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12552
更新日期:2019-10-01 00:00:00
abstract::Recent studies have described silver- and tau-positive glia and threads in the degenerating lesions of progressive supranuclear palsy. In this study, Gallyas-Braak silver impregnation and several immunohistochemical techniques were employed to examine the distribution of tangles, abnormal glia and threads in the cereb...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1995.tb01066.x
更新日期:1995-08-01 00:00:00