Abstract:
:Defects of mitochondrial function have been proposed as a potential mechanism in the development and pathogenesis of Alzheimer's disease (AD) and neuronal apoptosis. Mitochondrial enzyme-deficient pyramidal neurones are found in greater quantities in the hippocampus of AD patients than in age-matched controls. The presence of these neurones indicates that high levels of mutant mtDNA (mitochondrial DNA), sufficient to cause a biochemical deficiency within individual neurones, occur more frequently in AD than in normal ageing. This study analyses the relationship of cytochrome c oxidase (COX)-deficient neurones with the neuropathological markers of AD, neurofibrillary tangles (NFTs) and amyloid plaques, as well as markers of neuronal apoptosis known to occur in AD brains. Frozen sections of hippocampi from three AD patients were used to directly colocalize in situ the presence of histochemically COX-deficient neurones with immunohistology for the classical neuropathological markers of AD, tau and beta-amyloid. In addition, we also directly colocalized these mitochondrial-enzyme deficient neurones using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling and cleaved caspase-3. The distribution of amyloid plaques is anatomically distinct from the COX-deficient hippocampal pyramidal neurones and the neurones that contained NFTs or apoptotic labelling were always COX-positive. COX-deficient, succinate dehydrogenase-positive hippocampal neurones indicative of high mtDNA mutation load do not appear to be prone to apoptosis or to directly participate in the over production of tau or beta-amyloid. Biochemically significant mitochondrial defects do occur in AD and are likely to contribute to the overall central nervous system dysfunction in impairing neuronal function and possibly causing neurodegeneration via mechanisms other than apoptosis.
journal_name
Neuropathol Appl Neurobioljournal_title
Neuropathology and applied neurobiologyauthors
Cottrell DA,Borthwick GM,Johnson MA,Ince PG,Turnbull DMdoi
10.1046/j.1365-2990.2002.00414.xkeywords:
subject
Has Abstractpub_date
2002-10-01 00:00:00pages
390-6issue
5eissn
0305-1846issn
1365-2990pii
414journal_volume
28pub_type
杂志文章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: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:UNLABELLED:It is well known that glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for motoneurons. We have previously shown that it greatly enhanced motoneuron survival and axon regeneration after implantation of peripheral nerve graft following spinal root avulsion. AIMS:In the curre...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2012.01253.x
更新日期:2012-12-01 00:00:00
abstract::In many experimental models of skeletal muscle damage and in human muscle disease, empty basement membrane tubes remain following the destruction of muscle fibres. In the present study we test the hypothesis that the empty basement membrane tubes play an essential role in the orientation of regenerating muscle fibres....
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1990.tb01159.x
更新日期:1990-06-01 00:00:00
abstract::Sarcoplasmic masses contain disorganized myofibrillar material and are a striking feature of myotonic dystrophy. However their significance is still unclear. Using immunocytochemistry we studied the expression of cytoskeletal proteins (desmin and vimentin), dystrophin, markers of myogenic differentiation (foetal myosi...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2004.00602.x
更新日期:2005-02-01 00:00:00
abstract::The mechanisms underlying secondary or delayed cell death following traumatic brain injury (TBI) are poorly understood. Recent evidence from experimental models of TBI suggest that diffuse and widespread neuronal damage and loss is progressive and prolonged for months to years after the initial insult in selectively v...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2990.1998.00121.x
更新日期:1998-08-01 00:00:00
abstract::The brain is vulnerable to a number of acute insults, with traumatic brain injury being among the commonest. Neuroinflammation is a common response to acute injury and microglial activation is a key component of the inflammatory response. In the acute and subacute phase it is likely that this response is protective an...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/nan.12006
更新日期:2013-02-01 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::Dystrophic (D) and normal (N) chicken pectoral muscle was analysed for histopathological differences from the embryo (day 20) through to the mature adult stage. A variety of indices of structural changes were used, to express the progression quantitatively. At the embryonic stage, fibroblast numbers (but not satellite...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1983.tb00332.x
更新日期:1983-03-01 00:00:00
abstract:AIMS:HSPB8 is a small heat shock protein that forms a complex with the co-chaperone BAG3. Overexpression of the HSPB8-BAG3 complex in cells stimulates autophagy and facilitates the clearance of mutated aggregation-prone proteins, whose accumulation is a hallmark of many neurodegenerative disorders. HSPB8-BAG3 could thu...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2011.01198.x
更新日期:2012-02-01 00:00:00
abstract:AIMS:Resident and peripherally derived glioma associated microglia/macrophages (GAMM) play a key role in driving tumour progression, angiogenesis, invasion and attenuating host immune responses. Differentiating these cells' origins is challenging and current preclinical models such as irradiation-based adoptive transfe...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12489
更新日期:2019-02-01 00:00:00
abstract::Medulloblastomas (MBs) are malignant primitive neuroectodermal tumours (PNETs) of the cerebellum occurring predominantly in childhood. The association of monosomy of chromosome 22 with MB is controversial. Atypical teratoid/rhabdoid tumours (AT/RTs) of the brain share clinical and histological features with MBs and su...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.2002.00388.x
更新日期:2002-04-01 00:00:00
abstract::We present the clinical and neuropathological findings of a patient with early onset Alzheimer's dementia (AD), heterozygous carrier of the rare Apolipoprotein E Christchurch (APOEch) variant. The patient did not harbor any pathogenic mutation in known Mendelian genes related to AD or other neurodegenerative disorders...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12670
更新日期:2020-10-23 00:00:00
abstract::Apoptotic bodies are frequently found in oligodendrogliomas, particularly in the anaplastic subtype. A range of proteins, such as those of the Bcl family, are implicated in the control of apoptosis. The ratio of antagonists of apoptosis, such as Bcl-2, to agonists, such as Bax, is thought to determine the outcome for ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.1999.00199.x
更新日期:1999-10-01 00:00:00
abstract:AIMS:In Alzheimer's disease (AD), microglial activation prompted by the presence of amyloid has been proposed as an important contributor to the neurodegenerative process. Conversely following Aβ immunization, phagocytic microglia have been implicated in plaque removal, potentially a beneficial effect. We have investig...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2010.01156.x
更新日期:2011-08-01 00:00:00
abstract::Productive infection of the central nervous system by HIV predominantly involves the white matter and basal ganglia. Involvement of the cerebral cortex with neuronal loss is also described in AIDS patients but not in asymptomatic HIV-positive patients. The mechanism of neuronal damage is unknown. To enquire whether ne...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1995.tb01053.x
更新日期:1995-06-01 00:00:00
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:AIMS:Limb-girdle muscular dystrophy R9 (LGMDR9) is an autosomal recessive disorder caused by mutations in the fukutin-related protein gene (FKRP), encoding a glycosyltransferase involved in α-dystroglycan modification. Muscle atrophy, a significant feature of LGMDR9, occurs by a change in the normal balance between pro...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12684
更新日期:2020-12-18 00:00:00
abstract::Monolayer cultures of rat glial cells derived from 12 to 14 day fetal spinal cords and rat C6 glioma cells were examined for immunofluorescent reactivity with human or rabbit autoantibodies to intermediate filaments and with rabbit antibody to GFAP. The embryonic glial cells and C6 glima cells reacted identically with...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1980.tb00213.x
更新日期:1980-07-01 00:00:00
abstract:AIMS:The purpose of this study was to determine the functional recovery and protein regulation by transplanted induced pluripotent stem cells in a rat model of Huntington's disease (HD). METHODS:In a quinolinic acid-induced rat model of striatal degeneration, induced pluripotent stem cells were transplanted into the i...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12315
更新日期:2016-10-01 00:00:00
abstract:AIMS:Amyloid-β (Aβ) oligomers trigger synaptic degeneration that precedes plaque and tangle pathology. However, the signalling molecules that link Aβ oligomers to synaptic pathology remain unclear. Here, we addressed the potential role of RAPGEF2 as a novel signalling molecule in Aβ oligomer-induced synaptic and cognit...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12686
更新日期:2020-12-20 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::The avirulent demyelinating strain A7(74) of Semliki Forest virus after passage through mouse brain in vivo and mouse brain cell cultures has been shown to react immunologically with immune sera against galactocerebroside, glucocerebroside, total ganglioside and GT1b ganglioside but not against myelin or sulphatide . ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:
更新日期:1984-03-01 00:00:00
abstract::The spectrum of glioneuronal lesions underlying intractable epilepsies includes malformative pathologies like focal cortical dysplasia (FCD); and neoplastic lesions like gangliogliomas (GG) and dysembryoplastic neuroepithelial tumours (DNT). These may occur either singly or as dual lesions, having simultaneous presenc...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2006.00734.x
更新日期:2006-10-01 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::Adhalin and alpha-dystroglycan are two components of a complex of proteins that, in conjunction with dystrophin, provide a link between the subsarcolemmal cytoskeleton and the basal lamina of the extracellular matrix of skeletal muscle. In the absence of dystrophin, in Duchenne muscular dystrophy (DMD) and the mdx mou...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract:AIM:Peroxisomes play a key role in lipid metabolism, and peroxisome defects have been associated with neurodegenerative diseases such as X-adrenoleukodystrophy and Alzheimer's disease. This study aims to elucidate the contribution of peroxisomes in lipid alterations of area 8 of the frontal cortex in the spectrum of TD...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12681
更新日期:2020-12-17 00:00:00
abstract::The tight junction protein occludin 'glues' normal, adjacent brain microvessel endothelial cells together. Malignant brain tumours cause cerebral oedema because they have leaky endothelial tight junctions, which allow plasma fluid to enter the brain from the microvessel lumen. In order to identify molecular abnormalit...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.0305-1846.2001.00341.x
更新日期:2001-10-01 00:00:00
abstract::Studies in vitro have shown that phosphorylated translation initiation factor 2 alpha (TIF 2 alpha) may have several functions, including regulation of protein synthesis, control of cell death and procurement of resistance to oxidative stress in nerve cells. These properties may have implications in certain human neur...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.2002.t01-1-00410.x
更新日期:2002-12-01 00:00:00
abstract::Creutzfeldt-Jakob disease (CJD) is characterized by a loss of neurons accompanied by astrogliosis and spongiform changes in the neuropil. It has been recognized that reactive microglia occur in CJD but little is known about the regional distribution and extent of the microglial activation. We have, therefore, examined...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1995.tb01097.x
更新日期:1995-12-01 00:00:00