Chronic consumption ofAnnona muricatajuice triggers and aggravates cerebral tau phosphorylation in wild-type andMAPTtransgenic mice

2016 ◽  
Vol 139 (4) ◽  
pp. 624-639 ◽  
Author(s):  
Robert Rottscholl ◽  
Marlen Haegele ◽  
Britta Jainsch ◽  
Hong Xu ◽  
Gesine Respondek ◽  
...  
Keyword(s):  
Tau Phosphorylation ◽  
Wild Type

Effects of MDMA on neuroplasticity, amyloid burden and phospho-tau expression in APPswe/PS1dE9 mice

2019 ◽  
Vol 33 (9) ◽  
pp. 1170-1182 ◽  
Author(s):  
Sonia Abad ◽  
Carla Ramon-Duaso ◽  
Raúl López-Arnau ◽  
Jaume Folch ◽  
David Pubill ◽  
...  
Keyword(s):  
Recognition Memory ◽  
Specific Effect ◽  
Memory Deficits ◽  
Transgenic Mouse Model ◽  
Tau Phosphorylation ◽  
Amyloid Burden ◽  
Wild Type ◽  
Free Choline ◽  
Maladaptive Plasticity ◽  
Amyloid Cascade

Background: 3,4-Methylenedioxymethamphetamine (MDMA) is still one of the most consumed drugs by adolescents. Its abuse is related with cognitive impairment, which seems due to maladaptive plasticity and neural stress. In turn, new hypotheses suggest that Alzheimer’s disease (AD) may be promoted by neural stressors. Aims and methods: To test if there is an increase in vulnerability to AD after chronic MDMA consumption, we investigated the effects of this drug on recognition memory and its neurotoxic and neuroplastic effects in a transgenic mouse model of presymptomatic familiar AD (APP/PS1 dE9, Tg). Results: MDMA-treated animals showed recognition memory deficits, regardless of genotype, which were accompanied by changes in plasticity markers. Tg mice showed an impaired expression of Arc compared with wild-type animals, but exposure to MDMA induced an increase in the expression of this factor of the same percentage in both genotypes. However, the expression of c-fos, BDNF and p-CREB was not significantly altered by MDMA treatment in Tg mice. Although Tg mice had higher free choline levels than wild-type mice (about 123%), MDMA did not modify these levels in any case, ruling out any specific effect of this drug on the acetylcholine pathway. MDMA treatment significantly increased the presence of cortical amyloid plaques, as well as Aβ40, Aβ42 and secreted APPβ levels in Tg mice. These plaques were accompanied by increased tau phosphorylation (S199), which does not seem to occur via the canonic pathway involving AKT, CDK5 or GSK3β. Conclusions: The present results support previous evidences that MDMA can contribute to the amyloid cascade.

scholarly journals Estrogens Inhibit Amyloid-β-Mediated Paired Helical Filament-Like Conformation of Tau Through Antioxidant Activity and miRNA 218 Regulation in hTau Mice

2020 ◽  
Vol 77 (3) ◽  
pp. 1339-1351
Author(s):  
Michela Guglielmotto ◽  
Giusi Manassero ◽  
Valeria Vasciaveo ◽  
Marika Venezia ◽  
Massimo Tabaton ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Conformational Changes ◽  
Amyloid Β ◽  
Tau Phosphorylation ◽  
Paired Helical Filament ◽  
Wild Type ◽  
Aβ Peptides ◽  
Biological Sex ◽  
Nanomolar Concentration ◽  
Estradiol Levels

Background: The risk of developing Alzheimer’s disease as well as its progression and severity are known to be different in men and women, and cognitive decline is greater in women than in men at the same stage of disease and could be correlated at least in part on estradiol levels. Objective: In our work we found that biological sex influences the effect of amyloid-β42 (Aβ42) monomers on pathological tau conformational change. Methods: In this study we used transgenic mice expressing the wild-type human tau (hTau) which were subjected to intraventricular (ICV) injections of Aβ peptides in nanomolar concentration. Results: We found that Aβ42 produces pathological conformational changes and hyperphosphorylation of tau protein in male or ovariectomized female mice but not in control females. The treatment of ovariectomized females with estradiol replacement protects against the pathological conformation of tau and seems to be mediated by antioxidant activity as well as the ability to modulate the expression of miRNA 218 linked to tau phosphorylation. Conclusion: Our study indicates that factors as age, reproductive stage, hormone levels, and the interplay with other risk factors should be considered in women, in order to identify the best appropriate therapeutic approach in prevention of cognitive impairment.

scholarly journals Peripheral inflammation increases PKR activation, Tau phosphorylation and amyloid β production in wild-type mice

2013 ◽  
Vol 8 (Suppl 1) ◽  
pp. P32
Author(s):  
François Mouton-Liger ◽  
Anne-Sophie Rebillat ◽  
Clarisse Pace ◽  
Sarah Gourmaud ◽  
Mariko Taga ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Tau Phosphorylation ◽  
Peripheral Inflammation ◽  
Wild Type

P2-022: Peripheral inflammation increases PKR, GSK3β, and tau phosphorylation in wild-type mice

2013 ◽  
Vol 9 ◽  
pp. P352-P352
Author(s):  
Anne-Sophie Carret-Rebillat ◽  
François Mouton-Liger ◽  
Clarisse Pace ◽  
Sarah Gourmaud ◽  
Mariko TAGA ◽  
...  
Keyword(s):  
Tau Phosphorylation ◽  
Peripheral Inflammation ◽  
Wild Type

scholarly journals Sevoflurane Induces Tau Phosphorylation and Glycogen Synthase Kinase 3β Activation in Young Mice

2014 ◽  
Vol 121 (3) ◽  
pp. 510-527 ◽  
Author(s):  
Guorong Tao ◽  
Jie Zhang ◽  
Lei Zhang ◽  
Yuanlin Dong ◽  
Buwei Yu ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Interleukin 6 ◽  
Glycogen Synthase ◽  
Postsynaptic Density ◽  
Tau Phosphorylation ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Wild Type ◽  
Young Mice ◽  
Postsynaptic Density Protein

Abstract Background: Children with multiple exposures to anesthesia and surgery may have an increased risk of developing cognitive impairment. Sevoflurane is a commonly used anesthetic in children. Tau phosphorylation contributes to cognitive dysfunction. The authors therefore assessed the effects of sevoflurane on Tau phosphorylation and the underlying mechanisms in young mice. Methods: Six-day-old wild-type and Tau knockout mice were exposed to sevoflurane. The authors determined the effects of sevoflurane anesthesia on Tau phosphorylation, levels of the kinases and phosphatase related to Tau phosphorylation, interleukin-6 and postsynaptic density protein-95 in hippocampus, and cognitive function in both young wild-type and Tau knockout mice. Results: Anesthesia with 3% sevoflurane 2 h daily for 3 days induced Tau phosphorylation (257 vs. 100%, P = 0.0025, n = 6) and enhanced activation of glycogen synthase kinase 3β, which is the kinase related to Tau phosphorylation in the hippocampus of postnatal day-8 wild-type mice. The sevoflurane anesthesia decreased hippocampus postsynaptic density protein-95 levels and induced cognitive impairment in the postnatal day-31 mice. Glycogen synthase kinase 3β inhibitor lithium inhibited the sevoflurane-induced glycogen synthase kinase 3β activation, Tau phosphorylation, increased levels of interleukin-6, and cognitive impairment in the wild-type young mice. Finally, the sevoflurane anesthesia did not induce an increase in interleukin-6 levels, reduction in postsynaptic density protein-95 levels in hippocampus, or cognitive impairment in Tau knockout young mice. Conclusions: These data suggested that sevoflurane induced Tau phosphorylation, glycogen synthase kinase 3β activation, increase in interleukin-6 and reduction in postsynaptic density protein-95 levels in hippocampus of young mice, and cognitive impairment in the mice. Future studies will dissect the cascade relation of these effects.

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