scholarly journals Genotoxicity Studies of Titanium Dioxide Nanoparticles (TiO2NPs) in the Brain of Mice

Scientifica ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Hanan R. H. Mohamed ◽  
Nahed A. Hussien
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Titanium Dioxide ◽  
Brain Tissue ◽  
Titanium Dioxide Nanoparticles ◽  
Direct Sequencing ◽  
Disease Incidence ◽  
Dependent Manner ◽  
Toxic Potential ◽  
The Brain

Titanium dioxide nanoparticles (TiO2NPs) are excessively used and represent one of the top five most commonly used nanoparticles worldwide. Recently, various studies referred to their toxic potential on various organs using different treatment route. Male Swiss Webster mice were orally administrated TiO2NPs (500 mg/kg b.w.) daily for five consecutive days and then animals were sacrificed at 24 h, 7 days, or 14 days after the last treatment. The present results report that exposure to TiO2NPs produces mild to moderate changes in the cytoarchitecture of brain tissue in a time dependent manner. Moreover, Comet assay revealed the apoptotic DNA fragmentation, while PCR-SSCP pattern and direct sequencing showed point mutation of Presenilin 1 gene at exon 5, gene linked to inherited forms of the Alzheimer’s disease. Therefore, from these findings, the present study concluded that TiO2NPs is genotoxic and mutagenic to brain tissue which in turn might lead to Alzheimer’s disease incidence.

Intranasal administration of mitochondria improves spatial memory in olfactory bulbectomized mice

2021 ◽  
pp. 153537022110568
Author(s):  
Natalia V Bobkova ◽  
Daria Y Zhdanova ◽  
Natalia V Belosludtseva ◽  
Nikita V Penkov ◽  
Galina D Mironova
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Spatial Memory ◽  
Intranasal Administration ◽  
Brain Structures ◽  
Brain Regions ◽  
Dependent Manner ◽  
Behavioral Experiments ◽  
Hippocampal Cell Culture ◽  
The Brain

Here, we found that functionally active mitochondria isolated from the brain of NMRI donor mice and administrated intranasally to recipient mice penetrated the brain structures in a dose-dependent manner. The injected mitochondria labeled with the MitoTracker Red localized in different brain regions, including the neocortex and hippocampus, which are responsible for memory and affected by degeneration in patients with Alzheimer's disease. In behavioral experiments, intranasal microinjections of brain mitochondria of native NMRI mice improved spatial memory in the olfactory bulbectomized (OBX) mice with Alzheimer’s type degeneration. Control OBX mice demonstrated loss of spatial memory tested in the Morris water maze. Immunocytochemical analysis revealed that allogeneic mitochondria colocalized with the markers of astrocytes and neurons in hippocampal cell culture. The results suggest that a non-invasive route intranasal administration of mitochondria may be a promising approach to the treatment of neurodegenerative diseases characterized, like Alzheimer's disease, by mitochondrial dysfunction.

Exploring the brain tissue proteome of TgCRND8 Alzheimer's Disease model mice under B vitamin deficient diet induced hyperhomocysteinemia by LC-MS top-down platform

2019 ◽  
Vol 1124 ◽  
pp. 165-172
Author(s):  
Daniela Delfino ◽  
Diana Valeria Rossetti ◽  
Claudia Martelli ◽  
Ilaria Inserra ◽  
Federica Vincenzoni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Tissue ◽  
Disease Model ◽  
Top Down ◽  
Deficient Diet ◽  
B Vitamin ◽  
The Brain ◽  
Tissue Proteome

scholarly journals The Many Faces of Post-Ischemic Tau Protein in Brain Neurodegeneration of the Alzheimer’s Disease Type

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2213
Author(s):  
Ryszard Pluta ◽  
Stanisław J. Czuczwar ◽  
Sławomir Januszewski ◽  
Mirosław Jabłoński
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Tau Protein ◽  
Ischemia Reperfusion ◽  
Disease Type ◽  
Dependent Manner ◽  
Ischemic Brain ◽  
The Brain

Recent data suggest that post-ischemic brain neurodegeneration in humans and animals is associated with the modified tau protein in a manner typical of Alzheimer’s disease neuropathology. Pathological changes in the tau protein, at the gene and protein level due to cerebral ischemia, can lead to the development of Alzheimer’s disease-type neuropathology and dementia. Some studies have shown increased tau protein staining and gene expression in neurons following ischemia-reperfusion brain injury. Recent studies have found the tau protein to be associated with oxidative stress, apoptosis, autophagy, excitotoxicity, neuroinflammation, blood-brain barrier permeability, mitochondrial dysfunction, and impaired neuronal function. In this review, we discuss the interrelationship of these phenomena with post-ischemic changes in the tau protein in the brain. The tau protein may be at the intersection of many pathological mechanisms due to severe neuropathological changes in the brain following ischemia. The data indicate that an episode of cerebral ischemia activates the damage and death of neurons in the hippocampus in a tau protein-dependent manner, thus determining a novel and important mechanism for the survival and/or death of neuronal cells following ischemia. In this review, we update our understanding of proteomic and genomic changes in the tau protein in post-ischemic brain injury and present the relationship between the modified tau protein and post-ischemic neuropathology and present a positive correlation between the modified tau protein and a post-ischemic neuropathology that has characteristics of Alzheimer’s disease-type neurodegeneration.

Cerebrospinal Fluid pH and Monoamine and Glucolytic Metabolites in Alzheimer's Disease

1974 ◽  
Vol 124 (580) ◽  
pp. 280-287 ◽  
Author(s):  
C. G. Gottfries ◽  
Åke Kjällquist ◽  
Urban Pontén ◽  
B. E. Roos ◽  
G. Sundbärg
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Brain Tissue ◽  
Homovanillic Acid ◽  
Monoamine Metabolites ◽  
Hydroxyindoleacetic Acid ◽  
The Brain ◽  
Valid Information

Determinations of acid monoamine metabolites, such as homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), in cerebrospinal fluid (CSF) give valid information on the metabolism of the corresponding amines in the brain tissue (Moir et al., 1970; Roos, 1970). The monoamine metabolites in the CSF are related to age. The concentrations of HVA and 5-HIAA increase with age (Gottfries et al., 1971). Probenecid blocks the elimination of HVA and 5-HIAA from brain tissue to blood (Neff et al., 1964, 1967; Werdinius, 1966) and from CSF to blood (Guldberg et al., 1966; Olsson and Roos, 1968). Probenecid thus normally induces an increase in the concentrations of the acid monoamine metabolites in the CSF, which is related to the turnover of monoamines in the brain tissue.

Neuronal Development-Related miRNAs as Biomarkers for Alzheimer's Disease, Depression, Schizophrenia and Ionizing Radiation Exposure

2020 ◽  
Vol 28 (1) ◽  
pp. 19-52 ◽  
Author(s):  
Renu Chandra Segaran ◽  
Li Yun Chan ◽  
Hong Wang ◽  
Gautam Sethi ◽  
Feng Ru Tang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Radiation Exposure ◽  
Brain Tissue ◽  
Neuronal Development ◽  
Radiation Induced ◽  
The Common ◽  
Ionizing Radiation Exposure ◽  
Brain Radiation ◽  
The Brain

Radiation exposure may induce Alzheimer's disease (AD), depression or schizophrenia. A number of experimental and clinical studies suggest the involvement of miRNA in the development of these diseases, and also in the neuropathological changes after brain radiation exposure. The current literature review indicated the involvement of 65 miRNAs in neuronal development in the brain. In the brain tissue, blood, or cerebral spinal fluid (CSF), 11, 55, or 28 miRNAs are involved in the development of AD respectively, 89, 50, 19 miRNAs in depression, and 102, 35, 8 miRNAs in schizophrenia. We compared miRNAs regulating neuronal development to those involved in the genesis of AD, depression and schizophrenia and also those driving radiation-induced brain neuropathological changes by reviewing the available data. We found that 3, 11, or 8 neuronal developmentrelated miRNAs from the brain tissue, 13, 16 or 14 miRNAs from the blood of patient with AD, depression and schizophrenia respectively were also involved in radiation-induced brain pathological changes, suggesting a possibly specific involvement of these miRNAs in radiation-induced development of AD, depression and schizophrenia respectively. On the other hand, we noted that radiationinduced changes of two miRNAs, i.e., miR-132, miR-29 in the brain tissue, three miRNAs, i.e., miR- 29c-5p, miR-106b-5p, miR-34a-5p in the blood were also involved in the development of AD, depression and schizophrenia, thereby suggesting that these miRNAs may be involved in the common brain neuropathological changes, such as impairment of neurogenesis and reduced learning memory ability observed in these three diseases and also after radiation exposure.

scholarly journals Neuron-specific methylome analysis reveals epigenetic regulation and tau-related dysfunction of BRCA1 in Alzheimer’s disease

2017 ◽  
Vol 114 (45) ◽  
pp. E9645-E9654 ◽  
Author(s):  
Tatsuo Mano ◽  
Kenichi Nagata ◽  
Takashi Nonaka ◽  
Airi Tarutani ◽  
Tomohiro Imamura ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Tau Proteins ◽  
Epigenetic Mechanism ◽  
Dependent Manner ◽  
Brca1 Protein ◽  
Dna Methylome ◽  
Methylome Analysis ◽  
The Brain

Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by pathology of accumulated amyloid β (Aβ) and phosphorylated tau proteins in the brain. Postmortem degradation and cellular complexity within the brain have limited approaches to molecularly define the causal relationship between pathological features and neuronal dysfunction in AD. To overcome these limitations, we analyzed the neuron-specific DNA methylome of postmortem brain samples from AD patients, which allowed differentially hypomethylated region of the BRCA1 promoter to be identified. Expression of BRCA1 was significantly up-regulated in AD brains, consistent with its hypomethylation. BRCA1 protein levels were also elevated in response to DNA damage induced by Aβ. BRCA1 became mislocalized to the cytoplasm and highly insoluble in a tau-dependent manner, resulting in DNA fragmentation in both in vitro cellular and in vivo mouse models. BRCA1 dysfunction under Aβ burden is consistent with concomitant deterioration of genomic integrity and synaptic plasticity. The Brca1 promoter region of AD model mice brain was similarly hypomethylated, indicating an epigenetic mechanism underlying BRCA1 regulation in AD. Our results suggest deterioration of DNA integrity as a central contributing factor in AD pathogenesis. Moreover, these data demonstrate the technical feasibility of using neuron-specific DNA methylome analysis to facilitate discovery of etiological candidates in sporadic neurodegenerative diseases.

scholarly journals Spatiotemporal activation of the C/EBPβ/δ-secretase axis regulates the pathogenesis of Alzheimer’s disease

2018 ◽  
Vol 115 (52) ◽  
pp. E12427-E12434 ◽  
Author(s):  
Hualong Wang ◽  
Xia Liu ◽  
Shengdi Chen ◽  
Keqiang Ye
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Neuronal Loss ◽  
Brain Regions ◽  
Dependent Manner ◽  
Chronic Neuroinflammation ◽  
Factor C ◽  
The Brain ◽  
Ad Mouse Model

Alzheimer’s disease (AD) neuropathological hallmarks include senile plaques with aggregated amyloid beta as a major component, neurofibrillary tangles (NFT) containing truncated and hyperphosphorylated Tau, extensive neuronal loss, and chronic neuroinflammation. However, the key molecular mechanism that dominates the pathogenesis of AD remains elusive for AD. Here we show that the C/EBPβ/δ-secretase axis is activated in an age-dependent manner in different brain regions of the 3×Tg AD mouse model, elevating δ-secretase–truncated APP and Tau proteolytic truncates and promoting senile plaques and NFT formation in the brain, associated with gradual neuronal loss and chronic neuroinflammation. Depletion of inflammatory cytokine-regulated transcription factor C/EBPβ from 3×Tg mice represses APP, Tau, and δ-secretase expression, which subsequently inhibits APP and Tau cleavage, leading to mitigation of AD pathologies. Knockout of δ-secretase from 3×Tg mice strongly blunts AD pathogenesis. Consequently, inactivation of the C/EBPβ/δ-secretase axis ameliorates cognitive dysfunctions in 3×Tg mice by blocking APP and Tau expression and their pathological fragmentation. Thus, our findings support the notion that C/EBPβ/δ-secretase axis plays a crucial role in AD pathogenesis.

scholarly journals Differential Expression of mRNAs in the Brain Tissues of Patients with Alzheimer’s Disease Based on GEO Expression Profile and Its Clinical Significance

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Guowei Ma ◽  
Mingyan Liu ◽  
Ke Du ◽  
Xin Zhong ◽  
Shiqiang Gong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Differential Expression ◽  
Brain Tissue ◽  
Peripheral Blood ◽  
Bioinformatics Analysis ◽  
Venn Diagram ◽  
Ad Prevention ◽  
The Brain ◽  
Brain Tissues

Background. Early diagnosis of Alzheimer’s disease (AD) is an urgent point for AD prevention and treatment. The biomarkers of AD still remain indefinite. Based on the bioinformatics analysis of mRNA differential expressions in the brain tissues and the peripheral blood samples of Alzheimer’s disease (AD) patients, we investigated the target mRNAs that could be used as an AD biomarker and developed a new effective, practical clinical examination program. Methods. We compared the AD peripheral blood mononuclear cells (PBMCs) expression dataset (GEO accession GSE4226 and GSE18309) with AD brain tissue expression datasets (GEO accessions GSE1297 and GSE5281) from GEO in the present study. The GEO gene database was used to download the appropriate gene expression profiles to analyze the differential mRNA expressions between brain tissue and blood of AD patients and normal elderly. The Venn diagram was used to screen out the differential expression of mRNAs between the brain tissue and blood. The protein-protein interaction network map (PPI) was used to view the correlation between the possible genes. GO (gene ontology) and KEGG (Kyoto Gene and Genomic Encyclopedia) were used for gene enrichment analysis to determine the major affected genes and the function or pathway. Results. Bioinformatics analysis revealed that there were differentially expressed genes in peripheral blood and hippocampus of AD patients. There were 4958 differential mRNAs in GSE18309, 577 differential mRNAs in GSE4226 in AD PBMCs sample, 7464 differential mRNAs in GSE5281, and 317 differential mRNAs in GSE129 in AD brain tissues, when comparing between AD patients and healthy elderly. Two mRNAs of RAB7A and ITGB1 coexpressed in hippocampus and peripheral blood were screened. Furthermore, functions of differential genes were enriched by the PPI network map, GO, and KEGG analysis, and finally the chemotaxis, adhesion, and inflammatory reactions were found out, respectively. Conclusions. ITGB1 and RAB7A mRNA expressions were both changed in hippocampus and PBMCs, highly suggested being used as an AD biomarker with AD. Also, according to the results of this analysis, it is indicated that we can test the blood routine of the elderly for 2-3 years at a frequency of 6 months or one year. When a patient continuously detects the inflammatory manifestations, it is indicated as a potentially high-risk AD patient for AD prevention.

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