3xtg ad

The triple-transgenic mouse model of AD, B6;129-Psen1tm1Mpm Tg (APPSwe,tauP301L)1Lfa/J (namely, 3xTg-AD) and control wild-type animals were purchased from the Jackson Laboratory (Bar Harbor, Maine, USA). 3xTg-AD mice were previously characterized and represent a reliable model of human AD patients. In this model, Aβ intracellular immunoreactivity can be detected in some brain regions as early as 3 to 4 months of age [29 (link)]. Experiments were conducted using 8-week-old male mice (weight 15–25 g) in accordance with the guidelines of the European Communities Council (86/609/ECC) for the care and use of laboratory animals. Mice were housed in plastic (Makrolon) cages (four animals per cage) in a temperature-controlled room (21 ± 5 °C) and 60% humidity on 12 h light/dark inverted cycle (light was switched on at 8:00 P.M.) and maintained on laboratory diet (Mucedula, Italy) with water ad libitum. All appropriate measures were taken to minimize pain and discomfort in experimental animals.

3xTg-AD (Jackson Laboratory, Bar Harbor, ME, USA) is a transgenic mouse model for AD that expresses a chimeric mouse/human amyloid precursor protein (APP) containing the Swedish mutation, the M146V mutant form of human presenilin 1 (PS1), and a mutant form of tau (P301L) transgene. This mouse model develops AD-related abnormalities, including memory impairment, Aβ plaques, p-tau, and inflammation [27 (link)]. Non-transgenic control mice were maintained by crossing WT hybrid B6C3 mice with each other. All groups contained male and female mice with approximately 62–67% females. For this study, we used 17-month-old 3xTg-AD mice that exhibited substantial pathological and behavioral changes associated with AD. All animal procedures described in this article were in agreement with the regulations of the Center for Laboratory Animal Medicine and Care (CLAMC) and Animal Welfare Committee (AWC) of the University of Texas Medical School at Houston.

Mice homozygous for all three mutant alleles (3xTg AD; homozygous for the Psen1 mutation and homozygous for the co-injected APPSwe and tauP301L transgenes (Tg(APPSwe,tauP301L)1Lfa)) were obtained from the Jackson Laboratory. The 3xTg AD mice and age-matched C57 mice were housed in individually ventilated cages on standardized rodent bedding. Mice were housed under constant light cycle (12 h light/dark) with free food and water available. The 12.5-month-old 3×Tg AD mice were treated with Kaem or Rhap (100 mg kg⁻¹ d⁻¹) by oral gavage for 2 months, and subsequently evaluated for behavioural and molecular endpoints. All animal care and experimental procedures were approved by the Committee on the Ethics of Animal Experiments of the University of Macau (UMARE-013–2019).

Triple APP_swe, PS1_M146V and Tau_P301L transgenic mice (3xTg-AD) and wild-type (C57Bl/6) mice were obtained from Jackson Laboratory (Bar Harbor, Maine, USA) and then bred in a laboratory animal breeding room at the Korea Institute of Science and Technology. The mice were maintained at constant temperature with an alternating 12 hours light-dark cycle. Food and water were available ad libitum. Twenty-nine mice were assessed in this study; 14-months-old 3xTg-AD (n = 9; male 4, female 5) and wild-type (n = 5; male 3, female 2), 24-months-old 3xTg-AD (n = 8; male 4, female 4) and wild-type (n = 7; male 4, female 3). All animal experiments were performed in accordance with the National Institutes of Health guide for the care and use of laboratory animals (NIH Publications No. 8023, revised 1978). The animal studies were approved by the Institutional Animal Care and Use Committee of Korea Institute of Science and Technology.

Triple transgenic AD mice (3xTg-AD; strain: APPSwe, PS1M146V, and TauP301L) and wild-type (WT) mice (strain: B6129SF2/J) were purchased from the Jackson Laboratory (Maine, USA). We intraperitoneally injected 8 month-old female transgenic and wild mice with DAU (1 or 10 mg/kg) and saline of equivalent volume, respectively, for 2 months. Each group comprised 13 mice, and DAU dose was based on a previous study (Jin et al., 2010 (link)). The mouse age was based on the pathological stages of 3xTg-AD mice (Oddo et al., 2003 (link)). After 2 months of DAU treatment, cognitive abilities of all the animals were assessed. All animals were sacrificed after behavioral tests, for further studies. Animal experiments and manipulation were approved by the Shenzhen Center for Disease Control and Prevention. We made efforts to minimize animal suffering and reduce the number of mice used.

AD triple-transgenic mice, B6;129-Psen1tm1Mpm Tg (APPSwe, tauP301L) 1Lfa/J (named 3xTg-AD) and the wild-type B6129SF2 mice were purchased from the Jackson Laboratory (Bar Harbor, ME, USA). 3xTg-AD mice contain three mutations associated with frontotemporal dementia or familial AD (amyloid precursor protein [APP] Swe, tau MAPT P301L and presenilin-1 M146V). This reliable model of human AD displays both plaque and tangle pathology, with Aβ intracellular immunoreactivity detectable at three months of age and hyperphosphorylation of tau protein occurring by 12 to 15 months of age [18 (link)], reliably reproducing traits similar to those observed in the entire life of Alzheimer’s disease patients.
Experiments complied with the ARRIVE guidelines, in accordance with the EU Directive 2010/63/EU for animal experiments, and with a protocol approved by the Italian Ministry of Health (518/2018-PR). Mice were housed in plastic cages (Makrolon, Covestro A.G., Filago, Italy) in a temperature-controlled room (21 ± 5 °C) and 60% humidity on 12-hour light/dark reversed cycle (light was switched on at 8:00 p.m.) and maintained on standard laboratory diet (Mucedola, Settimo Milanese (MI), Italy) and water ad libitum. Appropriate measures minimized pain and discomfort in experimental animals.

3xTg-AD [with overexpression of APP(Swe), PSEN1(M146V), and MAPT(P301L) transgenes] and wild-type (WT) (B6129F2/J) breeders were purchased from Jackson Laboratory (Bar Harbor, Maine). All mice included in this study were bred in-house at the Biological Sciences Vivarium at Northern Arizona University. All mouse experiments were approved by the Institutional Animal Use and Care Committee (IACUC) of Northern Arizona University under protocol 18-016, and we adhered to the IACUC regulations and animal housing conditions. All experiments and reporting were carried out in accordance with ARRIVE guidelines and regulations (79 (link)).