1. Dehydroeffusol Pprevents Amyloid β1-42-mediated Hippocampal Neurodegeneration via Reducing Intracellular Zn2+ Toxicity
Haruna Tamano, Mako Takiguchi, Nana Saeki, Misa Katahira, Aoi Shioya, Yukino Tanaka, Mako Egawa, Toshiyuki Fukuda, Hiroki Ikeda, Atsushi Takeda Mol Neurobiol. 2021 Aug;58(8):3603-3613. doi: 10.1007/s12035-021-02364-3. Epub 2021 Mar 26.
Dehydroeffusol, a phenanthrene isolated from Juncus effusus, is a Chinese medicine. To explore an efficacy of dehydroeffusol administration for prevention and cure of Alzheimer's disease, here we examined the effect of dehydroeffusol on amyloid β1-42 (Aβ1-42)-mediated hippocampal neurodegeneration. Dehydroeffusol (15 mg/kg body weight) was orally administered to mice once a day for 6 days and then human Aβ1-42 was injected intracerebroventricularly followed by oral administration for 12 days. Neurodegeneration in the dentate granule cell layer, which was determined 2 weeks after Aβ1-42 injection, was rescued by dehydroeffusol administration. Aβ staining (uptake) was not reduced in the dentate granule cell layer by pre-administration of dehydroeffusol for 6 days, while increase in intracellular Zn2+ induced with Aβ1-42 was reduced, suggesting that pre-administration of dehydroeffusol prior to Aβ1-42 injection is effective for Aβ1-42-mediated neurodegeneration that was linked with intracellular Zn2+ toxicity. As a matter of fact, pre-administration of dehydroeffusol rescued Aβ1-42-mediated neurodegeneration. Interestingly, pre-administration of dehydroeffusol increased synthesis of metallothioneins, intracellular Zn2+-binding proteins, in the dentate granule cell layer, which can capture Zn2+ from Zn-Aβ1-42 complexes. The present study indicates that pre-administration of dehydroeffusol protects Aβ1-42-mediated neurodegeneration in the hippocampus by reducing intracellular Zn2+ toxicity, which is linked with induced synthesis of metallothioneins. Dehydroeffusol, a novel inducer of metallothioneins, may protect Aβ1-42-induced pathogenesis in Alzheimer's disease.
2. Beta-amyloid peptides(1-42) and (1-40) in the cerebrospinal fluid during pregnancy: a prospective observational study
Cristina Alomar-Dominguez, L Dostal, J Thaler, G Putz, C Humpel, W Lederer Arch Womens Ment Health. 2021 Jun;24(3):455-461. doi: 10.1007/s00737-020-01072-6. Epub 2020 Oct 2.
To evaluate changes in concentrations of selected biomarkers, neurotrophic factors, and growth factors in the cerebrospinal fluid during pregnancy. A prospective observational study was conducted in 32 pregnant women undergoing gynecological and obstetrical surgery under spinal anesthesia in a university hospital. Beta-amyloid(1-42) and beta-amyloid(1-40) peptides, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and vascular endothelial growth factor were analyzed in cerebrospinal fluid using an enzyme-linked immunosorbent assay. Eight women in second trimester pregnancy who underwent spinal anesthesia for gynecological or obstetrical surgery were compared with 24 matched women in third trimester pregnancies. CSF concentrations of beta-amyloid(1-42) were significantly higher in third trimester pregnancies (p = 0.025). During third trimester, the beta-amyloid ratio correlated with the vascular endothelial growth factor (rs = 0.657; p = 0.008). Higher concentrations of beta-amyloid(1-42) in cerebrospinal fluid of third trimester pregnancies and correlations between the beta-amyloid ratio and the vascular endothelial growth factor support the hypothesis that beta-amyloid peptides are involved in complex adaptive brain alterations during pregnancy.
3. Detection of microplastics in human lung tissue using μFTIR spectroscopy
Lauren C Jenner, Jeanette M Rotchell, Robert T Bennett, Michael Cowen, Vasileios Tentzeris, Laura R Sadofsky Sci Total Environ. 2022 Jul 20;831:154907. doi: 10.1016/j.scitotenv.2022.154907. Epub 2022 Mar 29.
Airborne microplastics (MPs) have been sampled globally, and their concentration is known to increase in areas of high human population and activity, especially indoors. Respiratory symptoms and disease following exposure to occupational levels of MPs within industry settings have also been reported. It remains to be seen whether MPs from the environment can be inhaled, deposited and accumulated within the human lungs. This study analysed digested human lung tissue samples (n = 13) using μFTIR spectroscopy (size limitation of 3 μm) to detect and characterise any MPs present. In total, 39 MPs were identified within 11 of the 13 lung tissue samples with an average of 1.42 ± 1.50 MP/g of tissue (expressed as 0.69 ± 0.84 MP/g after background subtraction adjustments). The MP levels within tissue samples were significantly higher than those identified within combined procedural/laboratory blanks (n = 9 MPs, with a mean ± SD of 0.53 ± 1.07, p = 0.001). Of the MPs detected, 12 polymer types were identified with polypropylene, PP (23%), polyethylene terephthalate, PET (18%) and resin (15%) the most abundant. MPs (unadjusted) were identified within all regions of the lung categorised as upper (0.80 ± 0.96 MP/g), middle/lingular (0.41 ± 0.37 MP/g), and with significantly higher levels detected in the lower (3.12 ± 1.30 MP/g) region compared with the upper (p = 0.026) and mid (p = 0.038) lung regions. After subtracting blanks, these levels became 0.23 ± 0.28, 0.33 ± 0.37 and 1.65 ± 0.88 MP/g respectively. The study demonstrates the highest level of contamination control and reports unadjusted values alongside different contamination adjustment techniques. These results support inhalation as a route of exposure for environmental MPs, and this characterisation of types and levels can now inform realistic conditions for laboratory exposure experiments, with the aim of determining health impacts.