Age-related autophagy alterations in the brain of senescence accelerated mouse prone 8 (SAMP8) mice

Abstract Background: Aging and age related diseases are strong risk factors for the development of neurodegenerative diseases. Neuroinflammation (NIF), as the brain's immune response, plays an important role in aged associated degeneration of central nervous system (CNS). The need of animal models that will allow us to understand and modulate this process is required for the scientific community. Methods: We have analyzed aging-phenotypical and inflammatory changes of brain myeloid cells (bMyC) in a senescent accelerated prone aged (SAMP8) mouse model, and compared with their resistant to senescence control (SAMR1). We have performed morphometric methods to evaluate the architecture of cellular prolongations and analyzed Iba1+ clustered cells with aging. To analyse specific constant brain areas we have performed stereology measurements of Iba1+ cells in the hippocampal formation. We have isolated bMyC from brain parenchyma (BP) and choroid plexus and meningeal membranes (m/Ch), and analyzed their response to systemic LPS- driven inflammation.Results: Aged 10 month old SAMP8 mice presents many of the hallmarks of aging-dependent neuroinflammation when compared with their senescence resistant control (SAMR1); ie, increase of protein aggregates, presence of Iba1+ clusters, but not increase in the number of Iba1+ cells. We have further observed and increased of main inflammatory mediator IL-1β, and augment of border MHCII+Iba1+ cells. Isolated CD45+ bMyC from brain parenchyma (BP) and choroid plexus and meningeal membranes (m/Ch) have been analyzed showing that there is not significant increase of CD45+ from the periphery. Our data support that aged-driven pro-inflammatory cytokine interleukin 1 beta (IL1β) transcription is mainly enhanced in CD45+BP cells. Furthermore, we are showing that LPS-driven systemic inflammation produces inflammatory cytokines mainly in the border bMyC, sensed to a lesser extent by the BP bMyC, and is enhanced in aged SAMP8 compared to control SAMR1.Conclusion: Our data validate the SAMP8 model to study age-associated neuroinflammatory events, but careful controls for age and strain are required. These animals show morphological changes in their bMyC cell repertoires associated to age, corresponding to an increase in the production of main pro inflammatory cytokines such as IL-1β, which predispose the brain to an enhanced inflammatory response after LPS-systemic challenge.

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Age-related changes in transmitter glutamate and NMDA receptor/channels in the brain of senescence-accelerated mouse

Neuroscience Letters ◽

10.1016/0304-3940(92)90396-o ◽

1992 ◽

Vol 137 (2) ◽

pp. 169-172 ◽

Cited By ~ 51

Author(s):

Yoshihisa Kitamura ◽

Xue-Hui Zhao ◽

Toshio Ohnuki ◽

Makiko Takei ◽

Yasuyuki Nomura

Keyword(s):

Nmda Receptor ◽

Age Related ◽

The Brain ◽

Senescence Accelerated Mouse ◽

Transmitter Glutamate ◽

Age Related Changes

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3,4-Dihydroxybenzalacetone (DBL) Prevents Aging-Induced Myocardial Changes in Senescence-Accelerated Mouse-Prone 8 (SAMP8) Mice

Cells ◽

10.3390/cells9030597 ◽

2020 ◽

Vol 9 (3) ◽

pp. 597

Author(s):

Vijayasree V. Giridharan ◽

Vengadeshprabhu Karupppagounder ◽

Somasundaram Arumugam ◽

Yutaka Nakamura ◽

Ashrith Guha ◽

...

Keyword(s):

Dna Damage ◽

Oxidative Dna Damage ◽

Cardiac Fibrosis ◽

Myocardial Dysfunction ◽

The Elderly ◽

Tunel Staining ◽

Inonotus Obliquus ◽

Age Related ◽

Samp8 Mice ◽

Senescence Accelerated Mouse

Aging is a predominant risk factor for the development and progression of cardiovascular complications. Physiologically and anatomically, the heart undergoes numerous changes that result in poor cardiac function in the elderly population. Recently, several studies have provided promising results, confirming the ability of the senescence-accelerated mouse-prone 8 (SAMP8) model to accurately model age-related cardiovascular alterations. In this study, using a murine model of senescence, SAMP8, we aimed to investigate the effect of 3,4-dihydroxybenzalacetone (DBL), a catechol-containing phenylpropanoid derivative isolated from Inonotus obliquus (Chaga), on cardiac aging. DBL was administered at the doses of 10 mg/kg and 20 mg/kg by oral gavage to SAMP8 mice to examine aging-mediated cardiac changes, such as oxidative DNA damage, oxygen radical antioxidant capacity (ORAC) value, fibrosis, inflammation, and apoptosis. The treatment with DBL at both doses significantly reduced aging-mediated oxidative DNA damage, and simultaneously increased the ORAC value in the SAMP8 assay. Cardiac fibrosis was assessed with Azan-Mallory staining, and the number of cardiac remodeling markers was found to be significantly reduced after the treatment with DBL. We also observed a decrease in cardiomyocyte apoptosis as measured by the terminal transferase-mediated dUTP nick end labeling (TUNEL) staining method and the caspase-3 levels in SAMP8 mice compared with senescence-resistant control (SAMR1) mice. The findings from this study suggest that DBL has a potentially beneficial effect on aging-mediated myocardial alterations. Further studies are warranted to confirm the promising potential of this catechol compound against aging-associated myocardial dysfunction.

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Lactobacillus paracasei PS23 Delays Progression of Age-Related Cognitive Decline in Senescence Accelerated Mouse Prone 8 (SAMP8) Mice

Nutrients ◽

10.3390/nu10070894 ◽

2018 ◽

Vol 10 (7) ◽

pp. 894 ◽

Cited By ~ 12

Author(s):

Shih-Yi Huang ◽

Li-Han Chen ◽

Ming-Fu Wang ◽

Chih-Chieh Hsu ◽

Ching-Hung Chan ◽

...

Keyword(s):

Cognitive Decline ◽

Brain Dysfunction ◽

Lactobacillus Paracasei ◽

Oxidative Enzymes ◽

Control Group ◽

Age Related ◽

Chemotactic Protein ◽

Age Related Cognitive Decline ◽

Samp8 Mice ◽

Senescence Accelerated Mouse

Probiotic supplements are potential therapeutic agents for age-related disorders due to their antioxidant and anti-inflammatory properties. However, the effect of probiotics on age-related brain dysfunction remains unclear. To investigate the effects of Lactobacillus paracasei PS23 (LPPS23) on the progression of age-related cognitive decline, male and female senescence-accelerated mouse prone 8 (SAMP8) mice were divided into two groups (n = 6 each): the control and PS23 groups. From the age of 16 weeks, these groups were given saline and LPPS23, respectively, because SAMP8 mice start aging rapidly after four months of age. After 12 weeks of treatment, we evaluated the effect of LPPS23 by analyzing their appearance, behavior, neural monoamines, anti-oxidative enzymes, and inflammatory cytokines. The PS23 group showed lower scores of senescence and less serious anxiety-like behaviors and memory impairment compared to the control group. The control mice also showed lower levels of neural monoamines in the striatum, hippocampus, and serum. Moreover, LPPS23 induced the anti-oxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). Higher levels of tumor necrosis factor (TNF)-α and monocyte chemotactic protein-1 (MCP1) and lower levels of interleukin (IL)-10 indicated that LPPS23 modulated the inflammation. Our results suggest that LPPS23 supplements could delay age-related cognitive decline, possibly by preventing oxidation and inflammation and modulating gut–brain axis communication.

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Age-related changes of mRNA expression of amyloid precursor protein in the brain of senescence-accelerated mouse

Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology ◽

10.1016/0305-0491(95)00090-9 ◽

1995 ◽

Vol 112 (2) ◽

pp. 399-404 ◽

Cited By ~ 3

Author(s):

Hyun-Sup Cho ◽

Sung-Soo Kim ◽

Woong Choi ◽

Seong-Hun Kim ◽

Sung-Jin Jeong ◽

...

Keyword(s):

Amyloid Precursor Protein ◽

Mrna Expression ◽

Precursor Protein ◽

Age Related ◽

The Brain ◽

Senescence Accelerated Mouse ◽

Age Related Changes

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Age-related changes in the oestrous cycle and reproductive hormones in senescence-accelerated mouse

Reproduction Fertility and Development ◽

10.1071/rd04099 ◽

2005 ◽

Vol 17 (5) ◽

pp. 507 ◽

Cited By ~ 10

Author(s):

Ma Yuan ◽

Zhou Wen-Xia ◽

Cheng Jun-Ping ◽

Zhang Yong-Xiang

Keyword(s):

Substance P ◽

Luteinising Hormone ◽

Reproductive Hormones ◽

Oestrous Cycle ◽

Reproductive Hormone ◽

Hormone Levels ◽

Age Related ◽

Samp8 Mice ◽

Senescence Accelerated Mouse ◽

Age Related Changes

To investigate age-related changes in the oestrous cycle and reproductive hormone levels in senescence-accelerated mouse (SAM), we examined these parameters in 3-, 5-, 7-, 9- and 11-month-old female SAM-prone/8 (SAMP8) and SAM-resistant/1 (SAMR1) strains. Levels of β-endorphin (β-EP) and substance P (SP) in the hypothalamus were also measured. The oestrous cycle and dioestrus of 9-month-old SAMP8 mice were significantly prolonged compared with age-matched SAMR1 mice. Furthermore, the concentration of serum oestradiol was lower and the level of pituitary luteinising hormone was higher in SAMP8 mice compared with SAMR1 mice. This characterises the hypothalamus–pituitary–ovary (HPO) axis of the SAMP8 strain as hypergonadotropic–hypogonad. The levels of β-EP and SP in the SAMP8 hypothalamus were lower than in the SAMR1 hypothalamus. These results indicate that the function of the HPO axis in SAMP8 mice declines early and this may be attributed, in part, to the decline in β-EP and SP concentrations in the hypothalamus.

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Erratum to: Age-related changes in the oestrous cycle and reproductive hormones in senescence-accelerated mouse

Reproduction Fertility and Development ◽

10.1071/rd04099_er ◽

2009 ◽

Vol 21 (4) ◽

pp. 624

Author(s):

Ma Yuan ◽

Zhou Wen-Xia ◽

Cheng Jun-Ping ◽

Zhang Yong-Xiang

Keyword(s):

Substance P ◽

Luteinising Hormone ◽

Reproductive Hormones ◽

Oestrous Cycle ◽

Reproductive Hormone ◽

Hormone Levels ◽

Age Related ◽

Samp8 Mice ◽

Senescence Accelerated Mouse ◽

Age Related Changes

To investigate age-related changes in the oestrous cycle and reproductive hormone levels in senescence-accelerated mouse (SAM), we examined these parameters in 3-, 5-, 7-, 9- and 11-month-old female SAM-prone/8 (SAMP8) and SAM-resistant/1 (SAMR1) strains. Levels of �-endorphin (�-EP) and substance P (SP) in the hypothalamus were also measured. The oestrous cycle and dioestrus of 9-month-old SAMP8 mice were significantly prolonged compared with age-matched SAMR1 mice. Furthermore, the concentration of serum oestradiol was lower and the level of pituitary luteinising hormone was higher in SAMP8 mice compared with SAMR1 mice. This characterises the hypothalamus.pituitary.ovary (HPO) axis of the SAMP8 strain as hypergonadotropic.hypogonad. The levels of �-EP and SP in the SAMP8 hypothalamus were lower than in the SAMR1 hypothalamus. These results indicate that the function of the HPO axis in SAMP8 mice declines early and this may be attributed, in part, to the decline in �-EP and SP concentrations in the hypothalamus.

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High Levels of β-Amyloid, Tau, and Phospho-Tau in Red Blood Cells as Biomarkers of Neuropathology in Senescence-Accelerated Mouse

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/5030475 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 9

Author(s):

Rebecca Piccarducci ◽

Deborah Pietrobono ◽

Carolina Pellegrini ◽

Simona Daniele ◽

Matteo Fornai ◽

...

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Inflammatory Marker ◽

Interleukin 1 ◽

Biochemical Alterations ◽

Amyloid A ◽

Accumulation Kinetics ◽

Samp8 Mice ◽

The Brain ◽

Senescence Accelerated Mouse

Alzheimer’s Disease (AD) is the most common Neurodegenerative Disease (ND), primarily characterised by neuroinflammation, neuronal plaques of β-amyloid (Aβ), and neurofibrillary tangles of hyperphosphorylated tau. α-Synuclein (α-syn) and its heteroaggregates with Aβ and tau have been recently included among the neuropathological elements of NDs. These pathological traits are not restricted to the brain, but they reach peripheral fluids as well. In this sense, Red Blood Cells (RBCs) are emerging as a good model to investigate the biochemical alterations of aging and NDs. Herein, the levels of homo- and heteroaggregates of ND-related proteins were analysed at different stages of disease progression. In particular, a validated animal model of AD, the SAMP8 (Senescence-Accelerated Mouse-Prone) and its control strain SAMR1 (Senescence-Accelerated Mouse-Resistant) were used in parallel experiments. The levels of the aforementioned proteins and of the inflammatory marker interleukin-1β (IL-1β) were examined in both brain and RBCs of SAMP8 and SAMR1 at 6 and 8 months. Brain Aβ, tau, and phospho-tau (p-tau) were higher in SAMP8 mice than in control mice and increased with AD progression. Similar accumulation kinetics were found in RBCs, even if slower. By contrast, α-syn and its heterocomplexes (α-syn-Aβ and α-syn-tau) displayed different accumulation kinetics between brain tissue and RBCs. Both brain and peripheral IL-1β levels were higher in SAMP8 mice, but increased sooner in RBCs, suggesting that inflammation might initiate at a peripheral level before affecting the brain. In conclusion, these results confirm RBCs as a valuable model for monitoring neurodegeneration, suggesting peripheral Aβ, tau, and p-tau as potential early biomarkers of AD.

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Noggin rescues age-related stem cell loss in the brain of senescent mice with neurodegenerative pathology

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1813205115 ◽

2018 ◽

Vol 115 (45) ◽

pp. 11625-11630 ◽

Cited By ~ 16

Author(s):

María Díaz-Moreno ◽

Tomás Armenteros ◽

Simona Gradari ◽

Rafael Hortigüela ◽

Laura García-Corzo ◽

...

Keyword(s):

Healthy Aging ◽

Late Onset ◽

Hippocampal Neurogenesis ◽

Bmp Signaling ◽

In Vitro Assays ◽

Age Related ◽

Samp8 Mice ◽

The Brain

Increasing age is the greatest known risk factor for the sporadic late-onset forms of neurodegenerative disorders such as Alzheimer’s disease (AD). One of the brain regions most severely affected in AD is the hippocampus, a privileged structure that contains adult neural stem cells (NSCs) with neurogenic capacity. Hippocampal neurogenesis decreases during aging and the decrease is exacerbated in AD, but the mechanistic causes underlying this progressive decline remain largely unexplored. We here investigated the effect of age on NSCs and neurogenesis by analyzing the senescence accelerated mouse prone 8 (SAMP8) strain, a nontransgenic short-lived strain that spontaneously develops a pathological profile similar to that of AD and that has been employed as a model system to study the transition from healthy aging to neurodegeneration. We show that SAMP8 mice display an accelerated loss of the NSC pool that coincides with an aberrant rise in BMP6 protein, enhanced canonical BMP signaling, and increased astroglial differentiation. In vitro assays demonstrate that BMP6 severely impairs NSC expansion and promotes NSC differentiation into postmitotic astrocytes. Blocking the dysregulation of the BMP pathway and its progliogenic effect in vivo by intracranial delivery of the antagonist Noggin restores hippocampal NSC numbers, neurogenesis, and behavior in SAMP8 mice. Thus, manipulating the local microenvironment of the NSC pool counteracts hippocampal dysfunction in pathological aging. Our results shed light on interventions that may allow taking advantage of the brain’s natural plastic capacity to enhance cognitive function in late adulthood and in chronic neurodegenerative diseases such as AD.

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