Estimating the Postmortem Interval of Carcasses in the Water Using the Carrion Insect, Brain Tissue RNA, Bacterial Biofilm, and Algae

The accurate estimation of postmortem interval (PMI) is crucial in the investigation of homicide cases. Unlike carcasses on land, various biological and abiotic factors affect the decomposition of carcasses in water. In addition, the insect evidence (e.g., blow flies) that is commonly used to estimate the PMI are unavailable before the carcasses float on water. Therefore, it is difficult to estimate the PMI of a carcass in water. This study aimed to explore an effective way of estimating the PMI of a carcass in water. Carrion insects, brain tissue RNA, bacterial biofilm on the skin surface, and algae in water with PMI were studied using 45 rat carcasses in a small river. The results showed that carrion insects might not be suitable for the estimation of PMI of a carcass in water since they do not have a regular succession pattern as a carcass on land, and the flies only colonized six of the carcasses. The target genes (β-actin, GAPDH, and 18S) in the brain tissue were associated with the PMI in a time-dependent manner within 1 week after death. A polynomial regression analysis was used to assess the relationship between the gene expression profiles and PMI. The correlation coefficient R2 of each regression equation was ≥ 0.924. A third-generation sequencing analysis showed that the bacteria on the skin surface of the carcass and the algae in the water samples around the carcass had a regular succession pattern, where Cryptomonas and Placoneis incased and decreased, respectively, within first 9 days. The results of this study provide a promising way to use the brain tissue RNA, bacterial biofilm, and algae to estimate the PMI of a carcass in water.

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Chemerin-induced macrophages pyroptosis in fetal brain tissue leads to cognitive disorder in offspring of diabetic dams

Journal of Neuroinflammation ◽

10.1186/s12974-019-1573-6 ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 1

Author(s):

Zhaoxia Liang ◽

Luyang Han ◽

Dianjianyi Sun ◽

Yanmin Chen ◽

Qi Wu ◽

...

Keyword(s):

Cognitive Impairment ◽

Brain Tissue ◽

Abdominal Cavity ◽

Behavioral Changes ◽

Dependent Manner ◽

Diabetes In Pregnancy ◽

The Impact ◽

The Brain ◽

In Pregnancy ◽

Brain Tissues

Abstract Background Chemerin is highly expressed in the serum, placenta tissue, and umbilical cord blood of diabetic mother; however, the impact of chemerin on cognitive disorders of offspring from mothers with diabetes in pregnancy remains unclear. Methods A diabetic phenotype in pregnant mice dams was induced by streptozocin (STZ) injection or intraperitoneal injection of chemerin. Behavioral changes in offspring of diabetic dams and nondiabetic controls were assessed, and changes in chemerin, two receptors of chemerin [chemerin receptor 23 (ChemR23) and chemokine (C-C motif) receptor-like 2 (CCRL2)], macrophages, and neurons in the brain tissue were studied to reveal the underlying mechanism of the behavioral changes. Results Chemerin treatment mimicked the STZ-induced symptom of maternal diabetes in mice along with the altered behavior of offspring in the open field test (OFT) assay. In the exploring process for potential mechanism, the brain tissues of offspring from chemerin-treated dams were observed with an increase level of macrophage infiltration and a decrease number of neuron cells. Moreover, an increased level of NOD-like receptor family pyrin domain containing 3 (NLRP3) and apoptosis-associated speck-like (Asc) protein as well as pyroptosis [characterized by increased active caspase-1 content and secretion of cytokines such as interleukin (IL) 1 beta (IL-1β) and IL-18] more activated in macrophages is also observed in the brain of these diabetic dam’s offspring, in the presence of ChemR23. In vitro, it was found that pyroptosis activation was increased in macrophages separated from the abdominal cavity of normal mice, after chemerin treatment. However, depletion of CCRL2 decreased the level of chemerin in the brain tissues of diabetic dams’ offspring; depletion of ChemR23 decreased macrophage pyroptosis, and depletion of either receptor reversed chemerin-mediated neurodevelopmental deficits and cognitive impairment of offspring of diabetic pregnant dams. Conclusions Chemerin induced diabetic pregnant disease and CCRL2 were required to enrich chemerin in the brain of offspring. Aggregation of chemerin could lead to macrophage recruitment, activation of pyroptosis, the release of inflammatory cytokines, a decrease in the number of neurons, and cognitive impairment in offspring in a ChemR23-dependent manner. Targeting CCRL2 and/or ChemR23 could be useful for treating neuropsychological deficits in offspring of dams with diabetes in pregnancy.

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Thiacloprid Induced Developmental Neurotoxicity via ROS-Oxidative Injury and Inflammation in Chicken Embryo: The Possible Attenuating Role of Chicoric and Rosmarinic Acids

Biology ◽

10.3390/biology10111100 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1100

Author(s):

Mayada R. Farag ◽

Samah R. Khalil ◽

Asmaa W. Zaglool ◽

Basma M. Hendam ◽

Amr A. Moustafa ◽

...

Keyword(s):

Brain Tissue ◽

Chicken Embryo ◽

Negative Impact ◽

Interleukin 1 ◽

Protein Carbonyl ◽

Myeloperoxidase Activity ◽

Dependent Manner ◽

In Ovo ◽

Necrosis Factor Alpha ◽

The Brain

Insecticides are widely employed in agriculture to control pests and as major factors for enhancing crop productivity. Thiacloprid (TH) is one of the most-used insecticides worldwide. In this study, the negative impact of TH on the brain tissue of developing chicken embryo models and the modulatory effect of chicoric (CA) and rosmarinic (RA) acids were investigated. The eggs were injected in ovo with different doses of TH (0.1, 1, 10, and 100 μg/egg). TH significantly increased the oxidative damage in the brain of exposed embryos in a dose-dependent manner (p < 0.05). TH significantly elevated the oxidative stress markers; protein carbonyl, malondialdehyde content, and DNA damage (p < 0.05). Myeloperoxidase activity and nitric oxide significantly increased with overexpression of the pro-inflammatory cytokines (interferon gamma, tumor necrosis factor alpha, and interleukin-1 beta) and stress-related and apoptotic genes (NF-KB, Caspase-3) in the brain tissue on both biochemical and molecular levels (p < 0.05), while downregulating the expression of antiapoptotic Bcl-2. Co-treatment of CA and RA with TH markedly decreased the insecticide-induced toxicity with a prominent synergistic effect (p < 0.05). In conclusion, TH is suggested to be a possible neurotoxic to embryos of vertebrates including human. The study also revealed the antioxidant, anti-inflammatory, genoprotective, and antiapoptotic property of CA and RA against TH toxicity.

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RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis

BioMed Research International ◽

10.1155/2017/8032910 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 13

Author(s):

Ryo Sato ◽

Teppei Nakano ◽

Mari Hosonaga ◽

Oltea Sampetrean ◽

Ritsuko Harigai ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastasis ◽

Cancer Cells ◽

Cancer Patients ◽

Rna Sequencing ◽

Brain Tissue ◽

Molecular Mechanisms ◽

Sequencing Analysis ◽

Primary Tumors ◽

The Brain

Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non–small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients.

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Sublethal doses of copper sulphate initiate deregulation of glial cytoskeleton, NF-kB and PARP expression in Capoeta umbla brain tissue

Regulatory Mechanisms in Biosystems ◽

10.15421/021916 ◽

2019 ◽

Vol 10 (1) ◽

pp. 103-110 ◽

Cited By ~ 2

Author(s):

M. Kirici ◽

V. S. Nedzvetsky ◽

C. A. Agca ◽

V. Y. Gasso

Keyword(s):

Toxic Effect ◽

Brain Tissue ◽

Copper Sulphate ◽

Copper Ions ◽

Dependent Manner ◽

Fish Brain ◽

Fish Group ◽

Tissue Cells ◽

Effect Of Copper ◽

The Brain

Copper sulphate pentahydrate (CuSO4∙5H2O) is widely used as a pesticide not only in agricultural but in aquaculture farming as well. Copper sulphate is a cheap chemical and able to contaminate the environment, especially water sources, which is crucial for fish harvesting and farming. The copper contamination in some areas is caused over decades because this pesticide has long been used everywhere. Copper ions inhibit invasive aquatic plants and many microorganisms but contaminate soil and natural water resources. The family of copper-containing chemicals is frequently used as algaecides in swimming pools. Despite the high toxicity of copper ions for fish in freshwater ponds, copper sulphate remains one of the prevalent pesticides in fish farming everywhere. High cytotoxicity and accumulation of the copper ions in sediments require study and calculation of the optimal dosage for its use as an antiseptic agent which will not have a detrimental effect on various tissue types of aquatic organisms. The main recognized mechanism which accompanies the toxic effect of copper ions is the generation of oxidative stress. Neural tissue cells are extremely susceptible to oxidative damage and the functions of the CNS are critical to the vitality of organisms. Glial cells maintain the structure and many vital functions of neurons. The cytoskeleton glial fibrillary acidic protein (GFAP), transcriptional nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and Poly(ADP-ribose) polymerase (PARP) are critical participants in a cellular response to a toxic agent impact. As this takes place, it could be applied in biomarking of heavy metal toxicity. In the presented study, we investigated the effects of copper ions on PARP, NF-kB, and GFAP expression in the Tigris scraper Capoeta umbla brain tissue. For 96 hours the fish were exposed to copper sulphate at sublethal concentrations, namely 1/2, 1/4 and 1/8 of the LD50 value. Western blot analysis of GFAP and PARP was used to assess further effects in the brain tissue. Every studied dose of copper significantly downregulated the expression of GFAP after 72 hours of treatment. In spite of the common increment in the GFAP content, 48 hours exposure to copper initiated the upregulation of that cytoskeleton marker. Moreover, treatment with copper sulphate induced several changes in the β-actin level, especially in the fish group treated for 72 hours. The observed effect of copper in the fish brain evidences the unspecific toxic effect of the copper ions in the brain tissue cells. The obtained results demonstrated meaningful disturbance in the expression of transcriptional factor NF-kB in the brain of the fish group exposed to copper. The changes found in the fish brain indicate the dose-dependent effect in a concentration range 185–740 µg/L of copper sulphate during 72 hours. However, the exposure to low dose of copper ions showed no effect in the fish group treated for 24 hours. Comparative analyses of the PARP content in the brain of fish exposed to copper for 72 hours was significantly less than in the groups treated with copper for both 24 and 48 hours. Thus, the copper ions in the dose range 185–740 µg/L can suppress PARP expression in a time-dependent manner. The results showed that copper ions could induce astroglial response accompanied by modulations of NF-kB and PARP-1 expression. The data obtained in this study suggest that copper sulphate has a significant effect on astrogliosis and DNA damage in the fish brain.

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

Scientifica ◽

10.1155/2016/6710840 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 4

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.

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Liquid Chromatography Analysis of Clozapine in Rat Brain Tissue, Using its Molecularly Imprinted Polymer after Administration of Toxic Dose of Drug and Lipid Emulsion Therapy

Current Pharmaceutical Analysis ◽

10.2174/1573412914666180111160741 ◽

2019 ◽

Vol 15 (3) ◽

pp. 251-257

Author(s):

Bahareh Sadat Yousefsani ◽

Seyed Ahmad Mohajeri ◽

Mohammad Moshiri ◽

Hossein Hosseinzadeh

Keyword(s):

Rat Brain ◽

Brain Tissue ◽

Molecularly Imprinted Polymer ◽

Lipid Emulsion ◽

Limit Of Detection ◽

Imprinted Polymer ◽

Toxic Dose ◽

Molecularly Imprinted ◽

The Brain ◽

Rat Brain Tissue

Background:Molecularly imprinted polymers (MIPs) are synthetic polymers that have a selective site for a given analyte, or a group of structurally related compounds, that make them ideal polymers to be used in separation processes.Objective:An optimized molecularly imprinted polymer was selected and applied for selective extraction and analysis of clozapine in rat brain tissue.Methods:A molecularly imprinted solid-phase extraction (MISPE) method was developed for preconcentration and cleanup of clozapine in rat brain samples before HPLC-UV analysis. The extraction and analytical process was calibrated in the range of 0.025-100 ppm. Clozapine recovery in this MISPE process was calculated between 99.40 and 102.96%. The limit of detection (LOD) and the limit of quantification (LOQ) of the assay were 0.003 and 0.025 ppm, respectively. Intra-day precision values for clozapine concentrations of 0.125 and 0.025 ppm were 5.30 and 3.55%, whereas inter-day precision values of these concentrations were 9.23 and 6.15%, respectively. In this study, the effect of lipid emulsion infusion in reducing the brain concentration of drug was also evaluated.Results:The data indicated that calibrated method was successfully applied for the analysis of clozapine in the real rat brain samples after administration of a toxic dose to animal. Finally, the efficacy of lipid emulsion therapy in reducing the brain tissue concentration of clozapine after toxic administration of drug was determined.Conclusion:The proposed MISPE method could be applied in the extraction and preconcentration before HPLC-UV analysis of clozapine in rat brain tissue.

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Serotonin elicits long-lasting enhancement of rhythmic respiratory activity in turtle brain stems in vitro

Journal of Applied Physiology ◽

10.1152/jappl.2001.91.6.2703 ◽

2001 ◽

Vol 91 (6) ◽

pp. 2703-2712 ◽

Cited By ~ 21

Author(s):

Stephen M. Johnson ◽

Julia E. R. Wilkerson ◽

Daniel R. Henderson ◽

Michael R. Wenninger ◽

Gordon S. Mitchell

Keyword(s):

Brain Stem ◽

Respiratory Activity ◽

Dependent Manner ◽

Frequency Increase ◽

Burst Frequency ◽

Bath Application ◽

Burst Amplitude ◽

Dose Dependent ◽

The Brain

Brain stem preparations from adult turtles were used to determine how bath-applied serotonin (5-HT) alters respiration-related hypoglossal activity in a mature vertebrate. 5-HT (5–20 μM) reversibly decreased integrated burst amplitude by ∼45% ( P < 0.05); burst frequency decreased in a dose-dependent manner with 20 μM abolishing bursts in 9 of 13 preparations ( P < 0.05). These 5-HT-dependent effects were mimicked by application of a 5-HT1A agonist, but not a 5-HT1B agonist, and were abolished by the broad-spectrum 5-HT antagonist, methiothepin. During 5-HT (20 μM) washout, frequency rebounded to levels above the original baseline for 40 min ( P < 0.05) and remained above baseline for 2 h. A 5-HT3 antagonist (tropesitron) blocked the post-5-HT rebound and persistent frequency increase. A 5-HT3 agonist (phenylbiguanide) increased frequency during and after bath application ( P < 0.05). When phenylbiguanide was applied to the brain stem of brain stem/spinal cord preparations, there was a persistent frequency increase ( P < 0.05), but neither spinal-expiratory nor -inspiratory burst amplitude were altered. The 5-HT3receptor-dependent persistent frequency increase represents a unique model of plasticity in vertebrate rhythm generation.

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Safety profile of the transcription factor EB (TFEB)-based gene therapy through intracranial injection in mice

Translational Neuroscience ◽

10.1515/tnsci-2020-0132 ◽

2020 ◽

Vol 11 (1) ◽

pp. 241-250

Author(s):

Zhenyu Li ◽

Guangqian Ding ◽

Yudi Wang ◽

Zelong Zheng ◽

Jianping Lv

Keyword(s):

Gene Therapy ◽

Transcription Factor ◽

Neurodegenerative Diseases ◽

Brain Tissue ◽

Inflammatory Responses ◽

Tissue Samples ◽

Protein Levels ◽

Virus Serotype ◽

Transcription Factor Eb ◽

The Brain

AbstractTranscription factor EB (TFEB)-based gene therapy is a promising therapeutic strategy in treating neurodegenerative diseases by promoting autophagy/lysosome-mediated degradation and clearance of misfolded proteins that contribute to the pathogenesis of these diseases. However, recent findings have shown that TFEB has proinflammatory properties, raising the safety concerns about its clinical application. To investigate whether TFEB induces significant inflammatory responses in the brain, male C57BL/6 mice were injected with phosphate-buffered saline (PBS), adeno-associated virus serotype 8 (AAV8) vectors overexpressing mouse TFEB (pAAV8-CMV-mTFEB), or AAV8 vectors expressing green fluorescent proteins (GFPs) in the barrel cortex. The brain tissue samples were collected at 2 months after injection. Western blotting and immunofluorescence staining showed that mTFEB protein levels were significantly increased in the brain tissue samples of mice injected with mTFEB-overexpressing vectors compared with those injected with PBS or GFP-overexpressing vectors. pAAV8-CMV-mTFEB injection resulted in significant elevations in the mRNA and protein levels of lysosomal biogenesis indicators in the brain tissue samples. No significant changes were observed in the expressions of GFAP, Iba1, and proinflammation mediators in the pAAV8-CMV-mTFEB-injected brain compared with those in the control groups. Collectively, our results suggest that AAV8 successfully mediates mTFEB overexpression in the mouse brain without inducing apparent local inflammation, supporting the safety of TFEB-based gene therapy in treating neurodegenerative diseases.

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High-fat diet-induced obesity and impairment of brain neurotransmitter pool

Translational Neuroscience ◽

10.1515/tnsci-2020-0099 ◽

2020 ◽

Vol 11 (1) ◽

pp. 147-160

Author(s):

Ranyah Shaker M. Labban ◽

Hanan Alfawaz ◽

Ahmed T. Almnaizel ◽

Wail M. Hassan ◽

Ramesa Shafi Bhat ◽

...

Keyword(s):

Oxidative Stress ◽

Brain Tissue ◽

High Fat Diet ◽

Density Lipoprotein ◽

Obese Group ◽

Control Group ◽

High Fat ◽

Brain Neurotransmitter ◽

The Brain ◽

Lean Group

AbstractObesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.

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UV-induced neuronal degeneration in the rat cerebral cortex

Cerebral Cortex Communications ◽

10.1093/texcom/tgab006 ◽

2021 ◽

Author(s):

Mariko Nakata ◽

Masayuki Shimoda ◽

Shinya Yamamoto

Keyword(s):

Uv Irradiation ◽

Neuronal Degeneration ◽

Uv Light ◽

Brain Lesion ◽

Terminal Deoxynucleotidyl Transferase ◽

Heme Oxygenase 1 ◽

Dependent Manner ◽

Focal Brain Injury ◽

The Brain ◽

And Oxidative Stress

Abstract Irradiation with ultraviolet (UV) light on the cortical surface can induce a focal brain lesion (UV lesion) in rodents. In the present study, we investigated the process of establishing a UV lesion. Rats underwent UV irradiation (365 nm wavelength, 2.0 mWh) over the dura, and time-dependent changes in the cortical tissue were analyzed histologically. We found that the majority of neurons in the lesion started to degenerate within 24 hours and the rest disappeared within 5 days after irradiation. UV-induced neuronal degeneration progressed in a layer-dependent manner. Moreover, UV-induced terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity and heme oxygenase-1 (HO-1) immunoreactivity were also detected. These findings suggest that UV irradiation in the brain can induce gradual neural degeneration and oxidative stress. Importantly, UV vulnerability may vary among cortical layers. UV-induced cell death may be due to apoptosis; however, there remains a possibility that UV-irradiated cells were degenerated via processes other than apoptosis. The UV lesion technique will not only assist in investigating brain function at a targeted site but may also serve as a pathophysiological model of focal brain injury and/or neurodegenerative disorders.

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