NeurodegenerationPub Date : 1996-06-01Epub Date: 2002-05-25DOI: 10.1006/neur.1996.0024
Lise Sofie Haug , Anne Carine Østvold , Richard F. Cowburn , Anita Garlind , Bengt Winblad , Nenad Bogdanovich , S.Ivar Walaas
{"title":"Decreased Inositol (1,4,5)-Trisphosphate Receptor Levels in Alzheimer's Disease Cerebral Cortex: Selectivity of Changes and Possible Correlation to Pathological Severity","authors":"Lise Sofie Haug , Anne Carine Østvold , Richard F. Cowburn , Anita Garlind , Bengt Winblad , Nenad Bogdanovich , S.Ivar Walaas","doi":"10.1006/neur.1996.0024","DOIUrl":"10.1006/neur.1996.0024","url":null,"abstract":"<div><p>We used immunoblotting and radioligand binding techniques to compare levels of the calcium-mobilizing receptor for the phosphoinositide hydrolysis-derived intracellular second messenger inositol (1,4,5)-trisphosphate (IP<sub>3</sub>) in post mortem samples from the temporal, frontal and parietal cortices of eight Alzheimer's disease (AD) and eight matched control cases. Immunoblotting with an antibody directed against the C-terminal end of the rat type I IP<sub>3</sub>-receptor showed that IP<sub>3</sub>-receptor protein levels were significantly reduced in the temporal (to 59 ± 6% of controls,<em>P</em>= 0.0002) and frontal (to 62 ± 10% of controls,<em>P</em>= 0.04), but not in the parietal cortices (to 63 ± 13% of controls,<em>P</em>= 0.1) of the AD cases, compared to controls. The number of [<sup>3</sup>H]IP<sub>3</sub>radioligand binding sites was significantly decreased in the temporal cortex, but not frontal and parietal cortices, of the AD brains. The decreased levels of both immunoreactive IP<sub>3</sub>-receptor protein and [<sup>3</sup>H]IP<sub>3</sub>binding in the temporal cortex correlated with a semi-quantitative score for the severity of AD neuropathology. No significant changes were seen in the levels of glial fibrillary acidic protein, synaptophysin or phosphate-activated glutaminase, as markers for astrocytes, neuronal vesicles and mitochondria, respectively. It is concluded that in affected AD brain regions, the IP<sub>3</sub>-receptor may represent a sensitive target for proteolysis, possibly mediated by activation of the Ca<sup>2+</sup>-activated neutral protease calpain. These degenerative changes may in part be responsible for the disruption of Ca<sup>2+</sup>homeostasis in AD-sensitive neurons.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 2","pages":"Pages 169-176"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19788833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurodegenerationPub Date : 1996-06-01Epub Date: 2002-05-25DOI: 10.1006/neur.1996.0023
Subramani Munirathinam, Madepalli K. Lakshmana, Trichur R. Raju
{"title":"(−) Deprenyl Attenuates Aluminium Induced Neurotoxicity in Primary Cortical Cultures","authors":"Subramani Munirathinam, Madepalli K. Lakshmana, Trichur R. Raju","doi":"10.1006/neur.1996.0023","DOIUrl":"10.1006/neur.1996.0023","url":null,"abstract":"<div><p>The role of (−) deprenyl in offering neuroprotection to cortical neurons exposed to Aluminium chloride (AlCl<sub>3</sub>) was examined. Primary cortical cultures derived from newborn rats were exposed to AlCl<sub>3</sub>on 6th day<em>in vitro</em>, at 100, 200, 400, 600, 800 and 1000 μM concentrations of AlCl<sub>3</sub>. After 48 h of AlCl<sub>3</sub>exposure, many nerve cell bodies were swollen; a beading of neurites and a disruption of the neuritic network were also observed suggesting neurodegeneration. Lactate dehydrogenase (LDH) efflux increased in a dose-dependent manner (59–120%). (−) Deprenyl co-exposure at concentrations of 10<sup>−7</sup>, 10<sup>−8</sup>and 10<sup>−9</sup>M significantly attenuated both the morphological alterations and the LDH efflux induced by AlCl<sub>3</sub>. This<em>in vitro</em>study has demonstrated that (−) deprenyl can protect neurons from aluminium induced neurotoxicity.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 2","pages":"Pages 161-167"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19788832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurodegenerationPub Date : 1996-06-01Epub Date: 2002-05-25DOI: 10.1006/neur.1996.0020
Anna Członkowska , Małgorzata Kohutnicka , Iwona Kurkowska-Jastrzębska , Andrzej Członkowski
{"title":"Microglial Reaction in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) Induced Parkinson's Disease Mice Model","authors":"Anna Członkowska , Małgorzata Kohutnicka , Iwona Kurkowska-Jastrzębska , Andrzej Członkowski","doi":"10.1006/neur.1996.0020","DOIUrl":"10.1006/neur.1996.0020","url":null,"abstract":"<div><p>We studied the microglial reaction in mice using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model for Parkinson's disease (PD). Microglial cells were identified by means of the Griffonia simplicifolia lectin (GSA-I-B<sub>4</sub>). Dopaminergic neurons were marked by tyrosine hydroxylase antibodies. Microglial activation was demonstrated by an increase in cellular number and changes of morphology (increased lectin staining, larger cell bodies and thicker processes) were seen in the substantia nigra from the 1st to the 14th day and in the striatum from the 1st to the 4th day after intoxication. Depletion of dopaminergic neurons was most pronounced 7 and 14 days following the treatment. The results suggest that microglial activation may be involved in the sequence of pathological changes that lead to dopaminergic neuronal damage after MPTP intoxication.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 2","pages":"Pages 137-143"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19788829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Improved Selectivity and Sensitivity in the Visualization of Neurofibrillary Tangles, Plaques and Neuropil Threads","authors":"Cullen K.M. , Halliday G.M. , Cartwright H. , Kril J.J.","doi":"10.1006/neur.1996.0025","DOIUrl":"10.1006/neur.1996.0025","url":null,"abstract":"<div><p>Stain sensitivity is a key factor in estimating the frequency of plaques and neurofibrillary tangles in Alzheimer's disease (AD), making it essential that the sensitivity and selectivity of detection methods for identifying these lesions is maximized. Several new, improved techniques have recently been described, although these methods have not been compared quantitatively with those techniques currently recommended for use in standardized diagnostic protocols. In the present study, eight different stains were examined for their selectivity and sensitivity in detecting plaques and tangles in serial tissue sections from AD and control brains. Techniques compared were immunohistochemistry for tau and β-amyloid, thioflavin S, nickel peroxidase method, and four silver impregnation techniques (Gallyas silver iodide, Campbell-Switzer-Martin, Garvey's modified Bielschowsky and methenamine silver methods). Among these eight staining techniques, the nickel peroxidase proved the most reliable method for the demonstration of the histopathological lesions of AD. This method labels all morphological types of plaques and tangles within a single tissue section, and provides several advantages for the analysis of lesion progression and distribution.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 2","pages":"Pages 177-187"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19788834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurodegenerationPub Date : 1996-06-01Epub Date: 2002-05-25DOI: 10.1006/neur.1996.0018
Philippe Anglade, Annick Mouatt-Prigent, Yves Agid, Etienne C. Hirsch
{"title":"Synaptic Plasticity in the Caudate Nucleus of Patients with Parkinson's Disease","authors":"Philippe Anglade, Annick Mouatt-Prigent, Yves Agid, Etienne C. Hirsch","doi":"10.1006/neur.1996.0018","DOIUrl":"10.1006/neur.1996.0018","url":null,"abstract":"<div><p>The loss of dopaminergic neurons from the substantia nigra in Parkinson's disease (PD) may provoke a reorganization of cellular interactions in the nigrostriatal pathway. Indeed, a plasticity of putative corticostriatal synapses has been evidenced in the striatum of rats with a 6-hydroxydopamine-induced lesion of the substantia nigra. However, to our knowledge, synaptic plasticity in the striatum has not previously been investigated in human PD. In this study, we have analysed, at electron microscope level, the morphological characteristics of the synapses formed by afferents in asymmetric contact with dendritic spines of neurons in the caudate nucleus of three patients with PD and three matched controls. The length of the postsynaptic densities and the number of perforated synapses were both significantly increased (24 and 88%, respectively) in the PD patients; the size of these afferents and the surface area occupied by their mitochondria also showed an increase (24 and 50%, respectively), although not statistically significant. The size and density of dendritic spines and the size of postsynaptic density perforations were unchanged. These data indicate the presence of plasticity of the putative corticostriatal synapses in PD and suggest a hyperactivity of cortical afferents to GABAergic neurons.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 2","pages":"Pages 121-128"},"PeriodicalIF":0.0,"publicationDate":"1996-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19788827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurodegenerationPub Date : 1996-03-01Epub Date: 2002-05-25DOI: 10.1006/neur.1996.0009
Clowry G.J., Sen P., Vrbová G.
{"title":"The Effects of an RNA Synthesis Inhibitor on the Survival and Regeneration of Rat Motoneurones Injured at Birth","authors":"Clowry G.J., Sen P., Vrbová G.","doi":"10.1006/neur.1996.0009","DOIUrl":"10.1006/neur.1996.0009","url":null,"abstract":"<div><p>This preliminary study aimed to test the proposal that neuronal death is triggered by expression of specific genes. In rat pups, the sciatic nerve was injured unilaterally on the first day after birth and actinomycin D, an RNA synthesis inhibitor, was administered 3 days later in a lower and higher dose to rat pups just prior to onset of motoneurone death induced by the lesion. Four weeks later, sciatic motoneurones from operated and contralateral pools were counted and their size measured. Significantly fewer motoneurones (16.7% ± 2.9 SD) survived when the animals were treated with a lower dose of the inhibitor compared to saline treated controls (36.6% ± 12.7 SD). Experiments recording tension generated in soleus muscle in response to sciatic nerve stimulation, at different ages following nerve crush, suggested that the treatment with the RNA synthesis inhibitor may have delayed regeneration of motor axons back to the muscle. However, survival of motoneurones after treatment with the higher dose did not differ significantly from controls (27.5% ± 1.3 SD. Nevertheless, the higher dose significantly reduced growth of motoneurones after 4 weeks. Therefore, the higher dose, although impeding normal development of motoneurones, is less neurotoxic than a lower dose. This suggests that a balancing of conflicting effects may have occurred. The neurodegenerative effects of delayed reinnervation induced by RNA synthesis inhibition may be balanced by some neuroprotective effects at a higher dose. More extensive studies are required to validate these pilot findings.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 1","pages":"Pages 65-71"},"PeriodicalIF":0.0,"publicationDate":"1996-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19704026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Substantia Nigra Pars Reticulata Neurons in Parkinson's Disease","authors":"Hardman C.D. , McRitchie D.A. , Halliday G.M. , Cartwright H.R. , Morris J.G.L.","doi":"10.1006/neur.1996.0007","DOIUrl":"10.1006/neur.1996.0007","url":null,"abstract":"<div><p>We have examined by immunohistochemistry the parvalbumin-containing neurons of the substantia nigra in patients with Parkinson's disease and in age-matched controls. Parvalbumin, a calcium binding protein, is involved in buffering intracellular calcium and in this study was localized within the majority of non-pigmented neurons of the human pars reticulata. Previous studies have shown that the parvalbumin-immunoreactive pars reticulata neurons are GABAergic and project to the motor thalamus and tectum. Their increased output, due to the loss of dopaminergic inhibition in Parkinson's disease, decreases cortical activation via thalamic pathways, causing parkinsonian symptoms. In Parkinson's disease there was a significant loss of parvalbumin-immunoreactivity from these neurons, though there was no evidence of actual cell loss. This loss of parvalbumin-immunoreactivity was detected only in those cases with end-stage Parkinson's disease.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 1","pages":"Pages 49-55"},"PeriodicalIF":0.0,"publicationDate":"1996-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19704024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association of Aβ40-positive Senile Plaques with Microglial Cells in the Brains of Patients with Alzheimer's Disease and in Non-demented Aged Individuals","authors":"Hiroaki Fukumoto , Asano Asami-Odaka , Nobuhiro Suzuki , Takeshi Iwatsubo","doi":"10.1006/neur.1996.0002","DOIUrl":"10.1006/neur.1996.0002","url":null,"abstract":"<div><p>To gain insight into the role of microglia in the formation of senile plaques (SP), especially in the generation of the two major molecular species of amyloid β protein (Aβ) with different carboxyl (C)-termini, Aβ40 and Aβ42(43), we conducted double immunolabelling studies on tissue sections from the brains of Alzheimer's disease (AD) and non-demented aged individuals using antibodies to the C-termini of Aβ and ferritin, a marker for microglia. All SP were Aβ42(43)-positive in AD as well as in non-demented individuals, only a proportion of which were Aβ40-positive. Both in AD and in non-demented individuals, approximately 2/3 of the Aβ40-positive SP were typical SP with amyloid cores, these being almost invariably associated with microglia. Aβ40-positive, uncored SP were also frequently associated with microglia (mean, 74%), whereas only 24% of Aβ40-negative, uncored SP contained microglia. These results suggest that microglia may play a role in the maturation of SP, especially in the generation of Aβ40.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 1","pages":"Pages 13-17"},"PeriodicalIF":0.0,"publicationDate":"1996-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19704730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurodegenerationPub Date : 1996-03-01Epub Date: 2002-05-25DOI: 10.1006/neur.1996.0001
James Hope , Mark S. Shearman , Helen C. Baxter , Angela Chong , Sharon M. Kelly , Nicholas C. Price
{"title":"Cytotoxicity of Prion Protein Peptide (PrP106–126) Differs in Mechanism from the Cytotoxic Activity of the Alzheimer's Disease Amyloid Peptide, Aβ25–35","authors":"James Hope , Mark S. Shearman , Helen C. Baxter , Angela Chong , Sharon M. Kelly , Nicholas C. Price","doi":"10.1006/neur.1996.0001","DOIUrl":"https://doi.org/10.1006/neur.1996.0001","url":null,"abstract":"<div><p>The abnormal form of the prion protein (PrP<sup>Sc</sup>), a synthetic prion protein peptide fragment (PrP<sup>106–126</sup>) and fragments of the Alzheimer's protein precursor, APP, have been shown to be cytotoxic<em>in vitro.</em>We have used synchronous, clonal cell models originally developed to study the toxicity of the Alzheimer's disease amyloid peptide, Aβ25–35, to investigate the actions of PrP peptides. We found that the cytotoxicity of the PrP<sup>106–126</sup>depends on its state of aggregation and the cellular expression of PrP<sup>C</sup>, and is independent of a loss of MTT reduction activity in the absence of cell death associated with the cellular effects of Aβ25–35. These factors may play a role in the lesion specificity of different pathological phenotypes of prion-protein related diseases.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 1","pages":"Pages 1-11"},"PeriodicalIF":0.0,"publicationDate":"1996-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72252217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurodegenerationPub Date : 1996-03-01Epub Date: 2002-05-25DOI: 10.1006/neur.1996.0003
Richard F. Cowburn , Birgitta Wiehager , Rivka Ravid , Bengt Winblad
{"title":"Acetylcholine Muscarinic M2 Receptor Stimulated [35S]GTPγS Binding Shows Regional Selective Changes in Alzheimer's Disease Postmortem Brain","authors":"Richard F. Cowburn , Birgitta Wiehager , Rivka Ravid , Bengt Winblad","doi":"10.1006/neur.1996.0003","DOIUrl":"https://doi.org/10.1006/neur.1996.0003","url":null,"abstract":"<div><p>Oxotremorine-M stimulated [<sup>35</sup>S]GTPγS binding was used to assess acetylcholine muscarinic M2 receptor mediated G-protein function in superior frontal cortical, superior temporal cortical and hippocampal membranes from a series of Alzheimer's disease and matched control subjects. No significant differences were seen in basal [<sup>35</sup>S]GTPγS binding between the groups. The maximal level of oxotremorine-M stimulated [<sup>35</sup>S]GTPγS binding over basal was significantly increased in Alzheimer's disease superior temporal cortex, suggesting an enhanced muscarinic M2 receptor-G-protein coupling efficiency in this region. In contrast, the maximal level of oxotremorine-M stimulated [<sup>35</sup>S]GTPγS binding over basal was unaltered in Alzheimer's disease superior frontal cortex and significantly reduced in Alzheimer's disease hippocampus. Western immunoblotting using antisera towards the α-subunits of those G-protein types known to couple muscarinic receptors, revealed that G<sub>qα</sub>and G<sub>iα</sub>, but not G<sub>oα</sub>, levels were significantly reduced in Alzheimer's disease superior temporal cortex. Neither G<sub>qα</sub>, G<sub>iα</sub>nor G<sub>oα</sub>levels were significantly altered in Alzheimer's disease superior frontal cortex or hippocampus. These results suggest that the efficacy of muscarinic M<sub>2</sub>receptor G-protein coupling shows regional selective changes in Alzheimer's disease postmortem brain with deficits occurring only in a region that shows severe pathology.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 1","pages":"Pages 19-26"},"PeriodicalIF":0.0,"publicationDate":"1996-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72252218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}