Stereological Changes in Microvascular Parameters in Hippocampus of a Transgenic Rat Model of Alzheimer’s Disease

Background: Microcirculatory factors play an important role in amyloid-β (Aβ)-related neuropathology in Alzheimer’s disease (AD). Transgenic (Tg) rat models of mutant Aβ deposition can enhance our understanding of this microvascular pathology. Objective: Here we report stereology-based quantification and comparisons (between- and within-group) of microvessel length and number and associated parameters in hippocampal subregions in Tg model of AD in Fischer 344 rats and non-Tg littermates. Methods: Systematic-random samples of tissue sections were processed and laminin immunostained to visualize microvessels through the entire hippocampus in Tg and non-Tg rats. A computer-assisted stereology system was used to quantify microvessel parameters including total number, total length, and associated densities in dentate gyrus (DG) and cornu ammonis (CA) subregions. Results: Thin hair-like capillaries are common near Aβ plaques in hippocampal subregions of Tg rats. There are a 53% significant increase in average length per capillary across entire hippocampus (p≤0.04) in Tg compared to non-Tg rats; 49% reduction in capillary length in DG (p≤0.02); and, higher microvessel density in principal cell layers (p≤0.03). Furthermore, within-group comparisons confirm Tg but not non-Tg rats have significant increase in number density (p≤0.01) and potential diffusion distance (p≤0.04) of microvessels in principal cell layers of hippocampal subregions. Conclusion: We show the Tg deposition of human Aβ mutations in rats disrupts the wild-type microanatomy of hippocampal microvessels. Stereology-based microvascular parameters could promote the development of novel strategies for protection and the therapeutic management of AD.

Download Full-text

Memory deficiency, cerebral amyloid angiopathy, and amyloid-β plaques in APP+PS1 double transgenic rat model of Alzheimer’s disease

PLoS ONE ◽

10.1371/journal.pone.0195469 ◽

2018 ◽

Vol 13 (4) ◽

pp. e0195469 ◽

Cited By ~ 6

Author(s):

Diana Klakotskaia ◽

Cansu Agca ◽

Rachel A. Richardson ◽

Edward G. Stopa ◽

Todd R. Schachtman ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebral Amyloid Angiopathy ◽

Rat Model ◽

Amyloid Β ◽

Transgenic Rat ◽

Amyloid Angiopathy ◽

Model Of Alzheimer’S Disease ◽

Cerebral Amyloid ◽

Transgenic Rat Model

Download Full-text

Neuronal and Astrocytic Metabolism in a Transgenic Rat Model of Alzheimer's Disease

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.37 ◽

2014 ◽

Vol 34 (5) ◽

pp. 906-914 ◽

Cited By ~ 41

Author(s):

Linn Hege Nilsen ◽

Menno P Witter ◽

Ursula Sonnewald

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Frontal Cortex ◽

Rat Model ◽

Hippocampal Formation ◽

Tricarboxylic Acid Cycle ◽

Amyloid Β ◽

Transgenic Rat ◽

Resonance Spectroscopy ◽

Model Of Alzheimer’S Disease

Regional hypometabolism of glucose in the brain is a hallmark of Alzheimer's disease (AD). However, little is known about the specific alterations of neuronal and astrocytic metabolism involved in homeostasis of glutamate and GABA in AD. Here, we investigated the effects of amyloid β (Aβ) pathology on neuronal and astrocytic metabolism and glial-neuronal interactions in amino acid neurotransmitter homeostasis in the transgenic McGill-R-Thyl-APP rat model of AD compared with healthy controls at age 15 months. Rats were injected with [1-13C]glucose and [1,2-13C]acetate, and extracts of the hippocampal formation as well as several cortical regions were analyzed using 1H- and 13C nuclear magnetic resonance spectroscopy and high-performance liquid chromatography. Reduced tricarboxylic acid cycle turnover was evident for glutamatergic and GABAergic neurons in hippocampal formation and frontal cortex, and for astrocytes in frontal cortex. Pyruvate carboxylation, which is necessary for de novo synthesis of amino acids, was decreased and affected the level of glutamine in hippocampal formation and those of glutamate, glutamine, GABA, and aspartate in the retrosplenial/cingulate cortex. Metabolic alterations were also detected in the entorhinal cortex. Overall, perturbations in energy- and neurotransmitter homeostasis, mitochondrial astrocytic and neuronal metabolism, and aspects of the glutamate-glutamine cycle were found in McGill-R-Thy1-APP rats.

Download Full-text

High‐Fat Diet Modulates Hepatic Amyloid β and Cerebrosterol Metabolism in the Triple Transgenic Mouse Model of Alzheimer’s Disease

Hepatology Communications ◽

10.1002/hep4.1609 ◽

2020 ◽

Author(s):

Cristina R. Bosoi ◽

Milène Vandal ◽

Marine Tournissac ◽

Manon Leclerc ◽

Hortense Fanet ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Transgenic Mouse ◽

High Fat Diet ◽

Amyloid Β ◽

Transgenic Mouse Model ◽

High Fat ◽

Model Of Alzheimer’S Disease ◽

Triple Transgenic Mouse

Download Full-text

Induced Pluripotent Stem Cell-Derived Neural Precursors Improve Memory, Synaptic and Pathological Abnormalities in a Mouse Model of Alzheimer’s Disease

Cells ◽

10.3390/cells10071802 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1802

Author(s):

Enrique Armijo ◽

George Edwards ◽

Andrea Flores ◽

Jorge Vera ◽

Mohammad Shahnawaz ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Symptoms ◽

Memory Loss ◽

Amyloid Β ◽

Cerebral Atrophy ◽

Brain Inflammation ◽

Neural Precursors ◽

Model Of Alzheimer’S Disease ◽

Induced Pluripotent

Alzheimer’s disease (AD) is the most common type of dementia in the elderly population. The disease is characterized by progressive memory loss, cerebral atrophy, extensive neuronal loss, synaptic alterations, brain inflammation, extracellular accumulation of amyloid-β (Aβ) plaques, and intracellular accumulation of hyper-phosphorylated tau (p-tau) protein. Many recent clinical trials have failed to show therapeutic benefit, likely because at the time in which patients exhibit clinical symptoms the brain is irreversibly damaged. In recent years, induced pluripotent stem cells (iPSCs) have been suggested as a promising cell therapy to recover brain functionality in neurodegenerative diseases such as AD. To evaluate the potential benefits of iPSCs on AD progression, we stereotaxically injected mouse iPSC-derived neural precursors (iPSC-NPCs) into the hippocampus of aged triple transgenic (3xTg-AD) mice harboring extensive pathological abnormalities typical of AD. Interestingly, iPSC-NPCs transplanted mice showed improved memory, synaptic plasticity, and reduced AD brain pathology, including a reduction of amyloid and tangles deposits. Our findings suggest that iPSC-NPCs might be a useful therapy that could produce benefit at the advanced clinical and pathological stages of AD.

Download Full-text

Gut Microbiota Alterations and Cognitive Impairment Are Sexually Dissociated in a Transgenic Mice Model of Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-201367 ◽

2021 ◽

pp. 1-20

Author(s):

Daniel Cuervo-Zanatta ◽

Jaime Garcia-Mena ◽

Claudia Perez-Cruz

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Gut Microbiota ◽

Cognitive Skills ◽

Amyloid Β ◽

Short Chain Fatty Acids ◽

Mice Model ◽

Model Of Alzheimer’S Disease ◽

Cognitive Deficiencies

Background: Normal aging is accompanied by cognitive deficiencies, affecting women and men equally. Aging is the main risk factor for Alzheimer’s disease (AD), with women having a higher risk. The higher prevalence of AD in women is associated with the abrupt hormonal decline seen after menopause. However, other factors may be involved in this sex-related cognitive decline. Alterations in gut microbiota (GM) and its bioproducts have been reported in AD subjects and transgenic (Tg) mice, having a direct impact on brain amyloid-β pathology in male (M), but not in female (F) mice. Objective: The aim of this work was to determine GM composition and cognitive dysfunction in M and F wildtype (WT) and Tg mice, in a sex/genotype segregation design. Methods: Anxiety, short term working-memory, spatial learning, and long-term spatial memory were evaluated in 6-month-old WT and Tg male mice. Fecal short chain fatty acids were determined by chromatography, and DNA sequencing and bioinformatic analyses were used to determine GM differences. Results: We observed sex-dependent differences in cognitive skills in WT mice, favoring F mice. However, the cognitive advantage of females was lost in Tg mice. GM composition showed few sex-related differences in WT mice. Contrary, Tg-M mice presented a more severe dysbiosis than Tg-F mice. A decreased abundance of Ruminococcaceae was associated with cognitive deficits in Tg-F mice, while butyrate levels were positively associated with better working- and object recognition-memory in WT-F mice. Conclusion: This report describes a sex-dependent association between GM alterations and cognitive impairment in a mice model of AD.

Download Full-text

Carboxy-Terminus Tau Protein Hyperphosphorylation is Associated with Extracellular Deposits of Amyloid-β Fibrillary in a Triple-Transgenic Model of Alzheimer’s Disease

Journal of Neurological Disorders ◽

10.4172/2329-6895.1000345 ◽

2017 ◽

Vol 05 (03) ◽

Author(s):

Miguel Angel Ontiveros Torres ◽

Leonel Castellanos Aguilar ◽

Jonathan Lennel Gutierrez Murcia ◽

Nayeli Martinez Zuniga ◽

Paola Flores Rodriguez ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Tau Protein ◽

Amyloid Β ◽

Carboxy Terminus ◽

Transgenic Model ◽

Model Of Alzheimer’S Disease

Download Full-text

GULP1/CED-6 ameliorates amyloid-β toxicity in a Drosophila model of Alzheimer’s disease

Oncotarget ◽

10.18632/oncotarget.20062 ◽

2017 ◽

Vol 8 (59) ◽

pp. 99274-99283 ◽

Cited By ~ 3

Author(s):

Wai Yin Vivien Chiu ◽

Alex Chun Koon ◽

Jacky Chi Ki Ngo ◽

Ho Yin Edwin Chan ◽

Kwok-Fai Lau

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Β ◽

Model Of Alzheimer’S Disease ◽

Drosophila Model

Download Full-text

Gestational Stress Augments Postpartum β-Amyloid Pathology and Cognitive Decline in a Mouse Model of Alzheimer’s Disease

Cerebral Cortex ◽

10.1093/cercor/bhy251 ◽

2018 ◽

Vol 29 (9) ◽

pp. 3712-3724 ◽

Cited By ~ 5

Author(s):

Zahra Jafari ◽

Jogender Mehla ◽

Bryan E Kolb ◽

Majid H Mohajerani

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Risk Factor ◽

Cognitive Decline ◽

Noise Exposure ◽

Amyloid Β ◽

Control Group ◽

Plaque Size ◽

Model Of Alzheimer’S Disease ◽

Gestational Stress

Abstract Besides well-known risk factors for Alzheimer’s disease (AD), stress, and in particular noise stress (NS), is a lifestyle risk factor common today. It is known that females are at a significantly greater risk of developing AD than males, and given that stress is a common adversity in females during pregnancy, we hypothesized that gestational noise exposure could exacerbate the postpartum development of the AD-like neuropathological changes during the life span. Pregnant APPNL-G-F/NL-G-F mice were randomly assigned to either the stress condition or control group. The stress group was exposed to the NS on gestational days 12–16, which resulted in a markedly higher hypothalamic–pituitary–adrenal (HPA) axis responsivity during the postpartum stage. Higher amyloid-β (Aβ) deposition and larger Aβ plaque size in the olfactory area were the early onset impacts of the gestational stress (GS) seen at the age of 4 months. This pattern of increased Aβ aggregation and larger plaque size were observed in various brain areas involved in both AD and stress regulation, especially in limbic structures, at the age of 6 months. The GS also produced anxiety-like behavior, deficits in learning and memory, and impaired motor coordination. The findings suggest that environmental stresses during pregnancy pose a potential risk factor in accelerating postpartum cognitive decline and AD-like neuropathological changes in the dams (mothers) later in life.

Download Full-text