P1-080: STUDY OF DAILY ORAL GENISTEIN ON SPATIAL AND OLFACTORY MEMORY IN WILD TYPE AND TRANSGENIC MICE THAT MODEL ALZHEIMER'S DISEASE

2006 ◽  
Vol 14 (7S_Part_5) ◽  
pp. P301-P302
Author(s):  
Alyson C. Williamson ◽  
Hayley R. LeBlanc ◽  
Brian G. Gentry ◽  
Craige C. Wrenn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Wild Type ◽  
Olfactory Memory

scholarly journals Arginase Inhibition Supports Survival and Differentiation of Neuronal Precursors in Adult Alzheimer’s Disease Mice

2020 ◽  
Vol 21 (3) ◽  
pp. 1133 ◽  
Author(s):  
Baruh Polis ◽  
Kolluru D. Srikanth ◽  
Vyacheslav Gurevich ◽  
Naamah Bloch ◽  
Hava Gil-Henn ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Adult Neurogenesis ◽  
Progenitor Cell ◽  
Molecular Mechanisms ◽  
Neuronal Cell ◽  
Cell Number ◽  
Wild Type ◽  
Newborn Neuron

Adult neurogenesis is a complex physiological process, which plays a central role in maintaining cognitive functions, and consists of progenitor cell proliferation, newborn cell migration, and cell maturation. Adult neurogenesis is susceptible to alterations under various physiological and pathological conditions. A substantial decay of neurogenesis has been documented in Alzheimer’s disease (AD) patients and animal AD models; however, several treatment strategies can halt any further decline and even induce neurogenesis. Our previous results indicated a potential effect of arginase inhibition, with norvaline, on various aspects of neurogenesis in triple-transgenic mice. To better evaluate this effect, we chronically administered an arginase inhibitor, norvaline, to triple-transgenic and wild-type mice, and applied an advanced immunohistochemistry approach with several biomarkers and bright-field microscopy. Remarkably, we evidenced a significant reduction in the density of neuronal progenitors, which demonstrate a different phenotype in the hippocampi of triple-transgenic mice as compared to wild-type animals. However, norvaline showed no significant effect upon the progenitor cell number and constitution. We demonstrated that norvaline treatment leads to an escalation of the polysialylated neuronal cell adhesion molecule immunopositivity, which suggests an improvement in the newborn neuron survival rate. Additionally, we identified a significant increase in the hippocampal microtubule-associated protein 2 stain intensity. We also explore the molecular mechanisms underlying the effects of norvaline on adult mice neurogenesis and provide insights into their machinery.

scholarly journals Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
T. Harach ◽  
N. Marungruang ◽  
N. Duthilleul ◽  
V. Cheatham ◽  
K. D. Mc Coy ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Transgenic Mice ◽  
Intestinal Microbiota ◽  
Neurodegenerative Disorder ◽  
Wild Type ◽  
Germ Free ◽  
Amyloid Pathology ◽  
Aβ Amyloid

Abstract Alzheimer’s disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer’s disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice. Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aβ amyloid pathology when compared to control mice with intestinal microbiota. Importantly, colonization of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased cerebral Aβ pathology, while colonization with microbiota from wild-type mice was less effective in increasing cerebral Aβ levels. Our results indicate a microbial involvement in the development of Abeta amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases.

P1-108: Effects of space radiation on hippocampal-dependent learning and neuropathology in wild-type and Alzheimer's disease transgenic mice

2013 ◽  
Vol 9 ◽  
pp. P190-P190 ◽  
Author(s):  
Juliet Moncaster ◽  
Mark Wojnarowicz ◽  
Srikant Sarangi ◽  
Andrew Fisher ◽  
Olga Minaeva ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Space Radiation ◽  
Wild Type ◽  
Dependent Learning

scholarly journals Adrenergic mechanisms of myocardium contractility regulation in genetic model of Alzheimer’s disease

2015 ◽  
Vol 96 (1) ◽  
pp. 50-55 ◽  
Author(s):  
A V Leushina ◽  
L F Nurullin ◽  
E O Petukhova ◽  
A L Zefirov ◽  
M A Mukhamedyarov
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Adrenergic Receptors ◽  
Myocardial Contractility ◽  
Genetic Model ◽  
Immunofluorescent Staining ◽  
Wild Type ◽  
Adrenergic Mechanisms ◽  
Model Of Alzheimer’S Disease

Aim. Study is aimed to investigate contractility impairments and receptor mechanisms of adrenergic regulation of myocardium inotropic function in Alzheimer’s disease model on transgenic mice.Methods. Experiments were performed on isolated preparations of atria and ventricles myocardium of mice. Transgenic mice of B6C3-Tg(APP695)85Dbo Tg(PSENI)85Dbo genotype were used as animal model of Alzheimer’s disease. Contractile responses of myocardium were registered by conventional myographic technique in isometric conditions. To evaluate the expression of adrenergic receptors, immunofluorescence staining of myocardium with specific antibodies was performed.Results. Transgenic mice showed not only a decreased effect of norepinephrine on myocardium inotropic function but also the inversion of the effect of norepinephrine - the use of 10-5-10-4 M of norepinephrine decreased myocardium inotropic function. Immunofluorescent staining showed decrease of expression of β1- and especially β2-adrenergic receptors ventricular myocardium of transgenic mice comparing to wild type mice. Adrenergic deregulation was registered in ventricles, but not in atria. The features of adrenergic regulatory mechanisms of myocardial contractility in transgenic APP/PS1 mice aged 8-10 months are specific, although somewhat similar to wild type mice aged 8-10 months, and are evidently due to Alzheimer’s disease. The inversion of norepinephrine inotropic effect (from positive to negative) may be explained by switching the intracellular cascade pathway of β2-adrenergic receptors effects to another type of G-protein.Conclusion. The results indicate that peripheral adrenergic mechanisms of myocardial contractility regulation are impaired in studied transgenic mice model of Alzheimer’s disease. Obtained data widen our understanding of Alzheimer’s disease pathogenesis, as well as our conception of relations between cardiovascular diseases and neurodegeneration.

scholarly journals Delta-secretase triggers Alzheimer’s disease pathologies in wild-type hAPP/hMAPT double transgenic mice

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Zhourui Wu ◽  
Xia Liu ◽  
Liming Cheng ◽  
Keqiang Ye
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Senile Plaques ◽  
Wild Type ◽  
Double Transgenic Mouse ◽  
Double Transgenic Mice ◽  
One Year ◽  
Aβ Production ◽  
Human Wild Type

AbstractAlzheimer’s disease (AD) is the most common neurodegenerative disease with multifactorial pathologies including Aβ containing senile plaques and neurofibrillary tangles (NFT) consisted of aggregated Tau. Most of the AD patients are sporadic and the familial mutation hereditary patients are composed only 1% of all cases. However, the current AD mouse models employ mutated APP, PS1, or even Tau mutant, in order to display a portion of AD pathologies. Delta-secretase (legumain, or asparaginyl endopeptidase, AEP) simultaneously cleaves both APP and Tau and augments Aβ production and Tau hyperphosphorylation and aggregation, contributing to AD pathogenesis. Here we show that δ-secretase is sufficient to promote prominent AD pathologies in wild-type hAPP/hMAPT double transgenic mice. We crossed hAPP l5 mice and hMAPT mice to generate double transgenic mouse model carrying both human wild-type APP and Tau. Compared to the single transgenic parents, these double transgenic mice demonstrated AD-related pathologies in one-year-old hAPP/hMAPT mice. Notably, overexpression of δ-secretase in hAPP/hMAPT double-transgenic mice evidently accelerated enormous senile plaques and NFT, associated with prominent synaptic defects and cognitive deficits. Hence, δ-secretase facilitates AD pathogenesis independent of any patient-derived mutation.

scholarly journals Ablation of the Locus Coeruleus Increases Oxidative Stress in Tg-2576 Transgenic but Not Wild-Type Mice

2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Orest Hurko ◽  
Kurt Boudonck ◽  
Cathleen Gonzales ◽  
Zoe A. Hughes ◽  
J. Steve Jacobsen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Locus Coeruleus ◽  
Intermediary Metabolism ◽  
Wild Type ◽  
Model Of Alzheimer’S Disease ◽  
Markers Of Oxidative Stress ◽  
Mutant Forms

Mice transgenic for production of excessive or mutant forms of beta-amyloid differ from patients with Alzheimer's disease in the degree of inflammation, oxidative damage, and alteration of intermediary metabolism, as well as the paucity or absence of neuronal atrophy and cognitive impairment. Previous observers have suggested that differences in inflammatory response reflect a discrepancy in the state of the locus coeruleus (LC), loss of which is an early change in Alzheimer's disease but which is preserved in the transgenic mice. In this paper, we extend these observations by examining the effects of the LC on markers of oxidative stress and intermediary metabolism. We compare four groups: wild-type or Tg2576 A transgenic mice injected with DSP4 or vehicle. Of greatest interest were metabolites different between ablated and intact transgenics, but not between ablated and intact wild-type animals. The Tg2576_DSP4 mice were distinguished from the other three groups by oxidative stress and altered energy metabolism. These observations provide further support for the hypothesis that Tg2576 A transgenic mice with this ablation may be a more congruent model of Alzheimer's disease than are transgenics with an intact LC.

scholarly journals Retinal Levels of Amyloid Beta Correlate with Cerebral Levels of Amyloid Beta in Young APPswe/PS1dE9 Transgenic Mice before Onset of Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Xi Mei ◽  
Mengxiang Yang ◽  
Lina Zhu ◽  
Qi Zhou ◽  
Xingxing Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Amyloid Beta ◽  
Early Stage ◽  
Degenerative Change ◽  
Cognitive Disorders ◽  
Inhibitory Effect ◽  
Early Age ◽  
Wild Type

Objectives. Retina abnormalities are related to cognitive disorders in patients with Alzheimer’s disease (AD). Retinal amyloid beta (Aβ) can be labeled by curcumin. We measured Aβ content in the cerebrum and retina of APPswe/PS1dE9 (APP) transgenic mice with early age to investigate the correlation between cerebrum and retina. Methods. APP mice and age-matched wild-type mice were investigated every month from age 2 months to 6 months to assess changes in Aβ content in the retina and cerebrum. At the beginning of each month, mice were fed a curcumin diet (50 mg/kg/day) for 7 consecutive days. The Aβ levels in the retina and cerebrum were measured by ELISAs. Correlations were identified between retinal and cerebral Aβ contents using Pearson’s correlation. Results. In the absence of curcumin, there was a significant correlation between Aβ contents in the retina and cerebrum of APP mice (r=0.7291, P=0.0014). With increasing age, Aβ-mediated degenerative change in the cerebrum (P<0.001 in 5 months) and retina (P<0.01 in 5 months) increased significantly. The inhibitory effect of curcumin on the Aβ level was significant in the cerebrum (P<0.001) and retina (P<0.01) of older APP mice in the early stage of life. Conclusion. We observed a significant correlation between the Aβ content in the retina and Aβ content in the cerebrum of APP mice. Our data suggest an appropriate time to measure retinal Aβ. Although curcumin can label Aβ in the retina, it also suppresses Aβ levels and weakens the degree of correlation between Aβ in cerebrum and retina tissues.

scholarly journals Arginase Inhibition Supports Survival and Differentiation of Neuronal Precursors in Adult Alzheimer’s Disease Mice

2019 ◽  
Author(s):  
Baruh Polis ◽  
Vyacheslav Gurevich ◽  
Naamah Bloch ◽  
Abraham O. Samson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Adult Neurogenesis ◽  
Progenitor Cell ◽  
Molecular Mechanisms ◽  
Neuronal Cell ◽  
Cell Number ◽  
Wild Type ◽  
Newborn Neuron

AbstractAdult neurogenesis is a complex physiological process, which plays a central role in maintaining cognitive functions, and consists of progenitor cell proliferation, newborn cell migration, and cell maturation. Adult neurogenesis is susceptible to alterations under various physiological and pathological conditions. A substantial decay of neurogenesis has been documented in Alzheimer’s disease (AD) patients and animal AD models; however, several treatment strategies can halt any further decline and even induce neurogenesis.Our previous results indicated a potential effect of arginase inhibition, with norvaline, on various aspects of neurogenesis in triple-transgenic mice. To better evaluate this effect, we chronically administer an arginase inhibitor, norvaline, to triple-transgenic and wild-type mice, and apply an advanced immunohistochemistry approach with several biomarkers and bright-field microscopy.Remarkably, we evidence a significant reduction in the density of neuronal progenitors, which demonstrate a different phenotype in the hippocampi of triple-transgenic mice as compared to wild-type animals. However, norvaline shows no significant effect upon the progenitor cell number and constitution. We demonstrate that norvaline treatment leads to an escalation of the polysialylated neuronal cell adhesion molecule immunopositivity, which suggests an improvement in the newborn neuron survival rate. Additionally, we identify a significant increase in the hippocampal microtubule-associated protein 2 stain intensity. We also explore the molecular mechanisms underlying the effects of norvaline on adult mice neurogenesis and provide insights into their machinery.

scholarly journals Knock-in models related to Alzheimer’s disease: synaptic transmission, plaques and the role of microglia

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Diana P. Benitez ◽  
Shenyi Jiang ◽  
Jack Wood ◽  
Rui Wang ◽  
Chloe M. Hall ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Synaptic Transmission ◽  
Amyloid Beta ◽  
Glutamate Release ◽  
Synaptic Function ◽  
Wild Type ◽  
Release Probability ◽  
Plaque Load

Abstract Background Microglia are active modulators of Alzheimer’s disease but their role in relation to amyloid plaques and synaptic changes due to rising amyloid beta is unclear. We add novel findings concerning these relationships and investigate which of our previously reported results from transgenic mice can be validated in knock-in mice, in which overexpression and other artefacts of transgenic technology are avoided. Methods AppNL-F and AppNL-G-F knock-in mice expressing humanised amyloid beta with mutations in App that cause familial Alzheimer’s disease were compared to wild type mice throughout life. In vitro approaches were used to understand microglial alterations at the genetic and protein levels and synaptic function and plasticity in CA1 hippocampal neurones, each in relationship to both age and stage of amyloid beta pathology. The contribution of microglia to neuronal function was further investigated by ablating microglia with CSF1R inhibitor PLX5622. Results Both App knock-in lines showed increased glutamate release probability prior to detection of plaques. Consistent with results in transgenic mice, this persisted throughout life in AppNL-F mice but was not evident in AppNL-G-F with sparse plaques. Unlike transgenic mice, loss of spontaneous excitatory activity only occurred at the latest stages, while no change could be detected in spontaneous inhibitory synaptic transmission or magnitude of long-term potentiation. Also, in contrast to transgenic mice, the microglial response in both App knock-in lines was delayed until a moderate plaque load developed. Surviving PLX5266-depleted microglia tended to be CD68-positive. Partial microglial ablation led to aged but not young wild type animals mimicking the increased glutamate release probability in App knock-ins and exacerbated the App knock-in phenotype. Complete ablation was less effective in altering synaptic function, while neither treatment altered plaque load. Conclusions Increased glutamate release probability is similar across knock-in and transgenic mouse models of Alzheimer’s disease, likely reflecting acute physiological effects of soluble amyloid beta. Microglia respond later to increased amyloid beta levels by proliferating and upregulating Cd68 and Trem2. Partial depletion of microglia suggests that, in wild type mice, alteration of surviving phagocytic microglia, rather than microglial loss, drives age-dependent effects on glutamate release that become exacerbated in Alzheimer’s disease.

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