Young SAMP8 Research Articles

Bangle (<i>Zingiber purpureum</i>) Extract Attenuates Insulin Resistance and Inflammation in the Skeletal Muscle of High Fat Diet-fed Young SAMP8 Mice

Insulin resistance induced by chronic inflammation enhances metabolic dysfunction in obesity. The aim of this study was to investigate the effects of Bangle (Zingiber purpureum) extract (Ba) on insulin resistance and inflammation in the gastrocnemius muscle (GM) of high-fat diet (HFD)-fed SAMP8 mice. Male mice were divided into three groups: HFD, HFD + 1%Ba, and + 2%Ba. The SAMP8 control (Con) and SAMR1 control (Rcon) were fed a low-fat diet. At week 26, plasma blood parameters, macrophage infiltration, levels of expression and phosphorylation of Akt, mTOR, and AMPK were examined. The levels of plasma glucose and insulin in the HFD group were significantly higher than those in the Con group. Conversely, these levels in the HFD + 2%Ba group were significantly lower than those in the HFD group. Treatment with 2% Ba suppressed the degree of macrophage infiltration induced by HFD in the GMs. The levels of phosphorylated Akt and mTOR were decreased and the levels of phosphorylated AMPK in the HFD + 2%Ba group were increased compared with those in the HFD group. Ba may attenuate HFD-induced insulin resistance and inflammation by modulating the AMPK/Akt/mTOR pathway in the GMs of HFD-fed young SAMP8 mice.

Abstract # 2050 The effect of Intranasal Insulin in the CNS in Alzheimer’s disease

Research on intranasal delivery of drugs, peptides, and proteins has grown over the past decade as an alternate way to deliver substrates to the brain. Recent work has shown intranasal delivery of insulin in humans improves memory and cognition in healthy subjects as well as patients with Alzheimer’s disease. However, the molecular mechanism for the beneficial effect of insulin on memory has yet to be elucidated. To determine how intranasal insulin may be improving cognition, we utilized the SAMP8 mouse model of Alzheimer’s disease. These mice are known to develop cognitive impairments by 9 months of age and intranasal insulin can improve memory in 12-month old mice. We performed RNA sequencing analysis on the hippocampus in young SAMP8 mice and aged SAMP8 mice treated with and without insulin. While many genes and pathways were changed in our comparisons, we found genes were predominantly upregulated in 3 key pathways with age and downregulated with insulin administration. These pathways include the T cell receptor signaling pathway, cytokine-cytokine receptor interaction, and cell adhesion molecule pathway. Based on these inflammatory pathways driven by gene changes, we further investigated the impact of intranasal insulin on brain inflammation. This work further shows the important role of insulin in improving memory.

Chronic noise exposure exacerbates AD-like neuropathology in SAMP8 mice in relation to Wnt signaling in the PFC and hippocampus

Non-genetic environmental hazards are thought to be associated with genetic susceptibility factors that increase Alzheimer’s disease (AD) pathogenesis. Aging and chronic noise exposure have been considered important factors in the AD. Here, we investigated the impact of chronic noise exposure on the AD-like neuropathology in the senescence-accelerated prone mouse (SAMP8) and the underlying mechanisms of such effects. We examined the consequences of AD-like neuropathology in 3-month-old SAMP8 mice using low- and high-intensity noise exposure and 8-month-old SAMP8 mice as aging positive controls. Immunoblotting and immunohistochemistry were conducted to examine AD-like pathological changes and potential mechanisms. Chronic noise exposure led to progressive overproduction of Aβ and increased the hyperphosphorylation of tau at Ser396, Thr205, and Thr231 sites in the hippocampus and the prefrontal cortex (PFC) in young SAMP8 mice, similar to that observed in aging SAMP8 mice. Both noise exposure and aging could cause a significant downregulation in Wnt signaling expression. These findings demonstrate that chronic noise stress exacerbated AD-like neuropathology, possibly by disrupting Wnt signaling and triggering aberrant tau hyperphosphorylation and Aβ in the PFC and hippocampus.

SPINGOSINE-1-PHOSPHATE RECEPTOR 5 AGONIST α-971432 IMPROVES LEARNING AND MEMORY IN THE SAMP8 MOUSE MODEL OF ALZHEIMER’S DISEASE

Sphingosine-1-phophate (S1P) is highly expressed in endothelial cells in the blood-brain barrier (BBB) and the brain. S1P has 5 subtype receptors (S1P1–5) which are involved in a host of cellular processes including cell proliferation, migration and survival. Reports indicate that a novel S1P5 compound A-971432 is highly effective in reversing lipid accumulation and age related cognitive decline in rats. This compound has bioavailability selectivity for the S1P5 receptor making it an attractive target for neurodegenerative diseases. In the current study, ten month old male SAMP8 mice were administered A-971432 via oral gavage 2ml/kg at (0, 0.03, 1 or 3 mg/kg) daily for the duration of the study. A young SAMP8 control group received vehicle for 10 weeks via oral gavage at 2ml/kg. Mice were tested in novel object recognition (NOR) during and T-maze foot shock avoidance during weeks 7–10 of treatment. At the end of behavior testing brain tissue was collected for biochemical analysis. In NOR the 12 month old mice that received A-971432 at 1mg/kg spent significantly more time with the novel object during the 24 hour retention test than the 12 month old SAMP8 mice that received vehicle (P<0.01). In the T-maze, the 12 month old mice that received A-971432 at 0.03 and 1 mg/kg took significantly fewer trials to make one avoidance than the 12 month old vehicle P<0.03 and P<0.01 respectively. On the one week retention test in the T-maze the mice which received 0.03 and 1 mg/kg took significantly fewer trials to make criterion (P<0.01). Analysis of the brain tissue indicated that the mice which received 1mg/kg had significantly lower total GSK-3β and 4-hydroxynoneal (HNE) than the mice which received vehicle (P<0.001) and (P<0.05) respectively. A-971432 improved learning and memory in both NOR and T-maze in the SAMP8 model of AD. Biochemical studies found that A-971432 decreased total GSK-3β which, in its phosphorylated form phosphorylates tau. A-971432 decreases lipid oxidation in the 12 month old SAMP8 mice a factor thought to be a primary site of action for the compound. The current results suggest that A-971432 may have therapeutic potential for AD.

Intranasal Insulin Transport is Preserved inAged SAMP8 Mice and is Altered by Albumin and Insulin Receptor Inhibition.

Insulin delivered to the level of the cribriform plate (intranasal insulin) is being investigated for its ability to enhance memory in people with Alzheimer's disease (AD). Recent work has shown intranasal insulin can be detected in young CD-1 mice within 5 min and is still present 60 min after injection. The current study determined whether intranasal insulin transport and the subsequent brain distribution of insulin varies in young, healthy mice (CD-1) compared to those with an AD-like phenotype (aged SAMP8) or those pre-disposed to develop such a phenotype (young SAMP8). We showed transport does not vary among these three mouse cohorts, suggesting that intranasal uptake and brain pharmacokinetics do not differ with AD-like signs or the genetic predisposition to developing them. We found that co-administration with bovine serum albumin increased levels of insulin in most brain regions. In addition, the insulin receptor inhibitor, S961, decreases the amount of insulin transported throughout the brain after intranasal injection. These results show insulin delivery to the brain by intranasal administration can be modified with agents such as albumin, may be dependent on the insulin receptor, and is not affected by an AD-like phenotype as presented by the SAMP8 mouse.

A comprehensive multiomics approach toward understanding the relationship between aging and dementia.

Because age is the greatest risk factor for sporadic Alzheimer's disease (AD), phenotypic screens based upon old age-associated brain toxicities were used to develop the potent neurotrophic drug J147. Since certain aspects of aging may be primary cause of AD, we hypothesized that J147 would be effective against AD-associated pathology in rapidly aging SAMP8 mice and could be used to identify some of the molecular contributions of aging to AD. An inclusive and integrative multiomics approach was used to investigate protein and gene expression, metabolite levels, and cognition in old and young SAMP8 mice. J147 reduced cognitive deficits in old SAMP8 mice, while restoring multiple molecular markers associated with human AD, vascular pathology, impaired synaptic function, and inflammation to those approaching the young phenotype. The extensive assays used in this study identified a subset of molecular changes associated with aging that may be necessary for the development of AD.

Regulation of the p19(Arf)/p53 pathway by histone acetylation underlies neural stem cell behavior in senescence-prone SAMP8 mice.

Brain aging is associated with increased neurodegeneration and reduced neurogenesis. B1/neural stem cells (B1-NSCs) of the mouse subependymal zone (SEZ) support the ongoing production of olfactory bulb interneurons, but their neurogenic potential is progressively reduced as mice age. Although age-related changes in B1-NSCs may result from increased expression of tumor suppressor proteins, accumulation of DNA damage, metabolic alterations, and microenvironmental or systemic changes, the ultimate causes remain unclear. Senescence-accelerated-prone mice (SAMP8) relative to senescence-accelerated-resistant mice (SAMR1) exhibit signs of hastened senescence and can be used as a model for the study of aging. We have found that the B1-NSC compartment is transiently expanded in young SAMP8 relative to SAMR1 mice, resulting in disturbed cytoarchitecture of the SEZ, B1-NSC hyperproliferation, and higher yields of primary neurospheres. These unusual features are, however, accompanied by premature loss of B1-NSCs. Moreover, SAMP8 neurospheres lack self-renewal and enter p53-dependent senescence after only two passages. Interestingly, in vitro senescence of SAMP8 cells could be prevented by inhibition of histone acetyltransferases and mimicked in SAMR1 cells by inhibition of histone deacetylases (HDAC). Our data indicate that expression of the tumor suppressor p19, but not of p16, is increased in SAMP8 neurospheres, as well as in SAMR1 neurospheres upon HDAC inhibition, and suggest that the SAMP8 phenotype may, at least in part, be due to changes in chromatin status. Interestingly, acute HDAC inhibition in vivo resulted in changes in the SEZ of SAMR1 mice that resembled those found in young SAMP8 mice.

TMJ Degeneration in SAMP8 Mice is Accompanied by Deranged Ihh Signaling

The temporomandibular joint (TMJ) functions as a load-bearing diarthrodial joint during mastication, and its continuous use and stress can lead to degeneration over age. Using senescence-accelerated (SAMP8) mice that develop early osteoarthritis-like changes in synovial joints at high frequency, we analyzed possible molecular mechanisms of TMJ degeneration and tested whether and how malocclusion may accelerate it. Condylar articular cartilage in young SAMP8 mice displayed early-onset osteoarthritic changes that included reductions in superficial/chondroprogenitor cell number, proteoglycan/collagen content, and Indian hedgehog (Ihh)-expressing chondrocytes. Following malocclusion induced by tooth milling, the SAMP8 condyles became morphologically defective, displayed even lower proteoglycan levels, and underwent abnormal chondrocyte maturation compared with malocclusion-treated condyles in wild-type mice. Malocclusion also induced faster progression of pathologic changes with increasing age in SAMP8 condyles as indicated by decreased PCNA-positive proliferating chondroprogenitors and increased TUNEL-positive apoptotic cells. These changes were accompanied by steeper reductions in Ihh signaling and by expression of matrix metalloproteinase 13 at the chondro-osseous junction in SAMP8 articular cartilage. In sum, we show for the first time that precocious TMJ degeneration in SAMP8 mice is accompanied by—and possibly attributable to—altered Ihh signaling and that occlusal dysfunction accelerates progression toward degenerative TMJ disease in this model.

Moderate Compared to Low Dietary Intake of trans‐Fatty Acids Impairs Strength of Old and Aerobic Capacity of Young SAMP8 Mice in Both Sexes

The senescence accelerated SAMP8 mouse is a model for sarcopenia and provides an opportunity to study the effects of lifelong dietary composition on the loss of physical function with age. We studied the effects of trans-fatty acids (2 % of total energy, TFA diet) on the loss of strength and aerobic exercise capacity (VO₂peak) with age. SAMP8 mice were studied at two ages (young, 25 weeks; old, 60 weeks) and on two diets (control vs TFA). Body composition, grip strength, VO₂peak, blood metabolites, and biochemical parameters were assessed. Body weight, fat mass, and body fat percentage all increased with age (p < 0.05) but were not significantly impacted by diet. There was a significant age-related decline in total grip strength as well as that normalized to fat-free mass (FFM) (p < 0.05) with a further decrease at old age in these metrics of strength on the TFA diet vs control diet (p < 0.05). Total VO₂peak exhibited no change with age or diet, but when normalized to FFM, VO₂peak exhibited age and TFA-related declines (p < 0.05). Intramuscular triacylglycerol (p < 0.05) and collagen content (p < 0.05) significantly increased with age, while blood triacylglycerol was increased by the TFA diet (p < 0.05). These data further characterize the SAMP8 mouse as a model for sarcopenia and indicate that dietary fatty acid composition can impact the degree of this age-related loss of physical function.

Alterations in local thyroid hormone signaling in the hippocampus of the SAMP8 mouse at younger ages: Association with delayed myelination and behavioral abnormalities

The senescence-accelerated mouse (SAM) strains were established through selective inbreeding of the AKR/J strain based on phenotypic variations of aging and consist of senescence-prone (SAMP) and senescence-resistant (SAMR) strains. Among them, SAMP8 is considered as a model of neurodegeneration displaying age-associated learning and memory impairment and altered emotional status. Because adult hypothyroidism is one of the common causes of cognitive impairment and various psychiatric disorders, we examined the possible involvement of thyroid hormone (TH) signaling in the pathological aging of SAMP8 using the senescence-resistant SAMR1 as control. Although plasma TH levels were similar in both strains, a significant decrease in type 2 deiodinase (D2) gene expression was observed in the SAMP8 hippocampus from 1 to 8 months of age, which led to a 35–50% reductions at the protein level and 20% reduction of its enzyme activity at 1, 3, and 5 months. D2 is responsible for local conversion of thyroxine into transcriptionally active 3,5,3′-triiodothyronine (T3), so the results suggest a reduction in T3 level in the SAMP8 hippocampus. Attenuation of local TH signaling was confirmed by downregulation of TH-dependent genes and by immunohistochemical demonstration of delayed and reduced accumulation of myelin basic protein, the expression of which is highly dependent on TH. Furthermore, we found that hyperactivity and reduced anxiety were not age-associated but were characteristic of young SAMP8 before they start showing impairments in learning and memory. Early alterations in local TH signaling may thus underlie behavioral abnormalities as well as the pathological aging of SAMP8. © 2012 Wiley Periodicals, Inc.

The effect of diminished osteogenic signals on reduced osteoporosis recovery in aged mice and the potential therapeutic use of adipose-derived stem cells

Adipose-derived stem cells (ADSCs) have been shown to be pluoripotent and explored for their usage in tissue engineering. Previously, we have established a cell-based approach comprised of platelet-enriched plasma and osteo-progenitor cells for treating osteoporosis in an ovariectomized-senescence-accelerated mice (OVX-SAMP8) model. In the present study, we intend to explore the feasibility of using ADSCs as a cell-based therapeutic approach for treating osteoporosis, and to examine the effects of aging on the pluoripotency of ADSCs and the efficiency of bone formation both in vitro and in vivo. Flow cytometry was used to characterize ADSCs isolated from young and aged female SAMP8 mice and showed that the highly positive expression of surface markers such as CD44 and CD105 and negative for CD34 and CD45. Therefore, to compare the aging effects on the growth kinetics and differentiation potential of young and aged ADSCs, we found that there was a significant decline in both the proliferation rate (approximately 13.3%) and osteo-differentiation potential in aged ADSC. Subsequently, young and aged ADSCs were transplanted into the bone marrow of osteoporotic mice (OVX-SAMP8) to evaluate their bone formation ability. ADSC transplants were shown effective in restoring bone mineral density in the right/left knees, femurs and spine, 4 months post-transplantation; mice which received young ADSC transplants showed significantly higher bone regeneration（an average of 24.3% of improved BMD） over those received aged ADSCs. In conclusion, these findings showed that aging impedes osteoporosis-ameliorating potential of ADSC by diminishing osteogenic signal, and that ADSC could be used as a potential cell-based therapy for osteoporosis.

Effects of ZSET1446/ST101 on Cognitive Deficits and Amyloid β Deposition in the Senescence Accelerated Prone Mouse Brain

The senescence accelerated prone mouse strain 8 (SAMP8) develops age-related deficits in learning and memory. Effects of the azaindolizinone derivative ZSET1446/ST101, a newly synthesized cognitive enhancer, on cognitive impairment and deposition of amyloid β (Aβ) were assessed in the SAMP8. ZSET1446 was administered in drinking water at estimated doses of 0.002, 0.01, and 0.1 mg/kg per day from the age of 8 months. The SAMP8 at the age of 8 months showed cognitive impairment in a novel object recognition task compared with young SAMP8 at the age of 8 weeks. Further, grading scores were gradually increased from 9 to 12 months and Aβ-like immunoreactivity in the hippocampus was increased at the age of 10 months. ZSET1446 ameliorated cognitive deficits of SAMP8 after 4, 8, 12, and 16 weeks of treatment in a novel object recognition test. ZSET1446 also reduced grading scores of SAMP8 after 16 weeks of treatment. Further, 8-week treatment of ZSET1446 significantly reduced the total number of Aβ-positive granules in the hippocampus. These results suggest that ZSET1446 shows ameliorating effects on SAMP8 partly due to the suppression of an increase of Aβ-deposition in the hippocampus.

Aging Is Associated With a Shift of Fatty Metabolism Toward Lipogenesis

The incidence of nonalcoholic fatty liver disease is steadily increasing among the elderly population. Lipid metabolism is transcriptionally controlled by the nuclear receptors retinoid acid receptor alpha, liver-X-receptor alpha, and peroxisome proliferator-activated receptor alpha and their target genes ABCA1, sterol regulatory element-binding protein-1c, and fatty acid synthase. Using senescence-accelerated prone mice (SAMP8), we addressed the question as to whether age-related increase of oxidative stress affects nuclear receptor gene expression. In contrast to SAMR1 control mice, young SAMP8 mice exhibit hepatic steatosis with increased hepatic cholesterol content, plasma triglyceride, and aspartate aminotransferase levels. This is accompanied by an increase of liver-X-receptor alpha and retinoid acid receptor alpha expression, whereas peroxisome proliferator-activated receptor alpha expression is found diminished. SAMP8 mice further reveal a lower expression of ABCA1 as well as of sterol regulatory element-binding protein-1c and higher expression of fatty acid synthase. The dysbalance between the nuclear receptors and their target genes most probably mediates hepatic steatosis and underlines the pathological relevance of nuclear receptor shift toward lipogenesis in fat metabolism of the elderly patient.

Nuclear but Not Mitochondrial DNA Involvement in Respiratory Complex I Defects Found in Senescence-Accelerated Mouse Strain, SAMP8

This study determined pathogenicity of an A11181G mtDNA mutation found in a senescence-accelerated mouse strain, SAMP8. The mutation was at a highly conserved site of the mt-Nd4 gene, which encodes one of the respiratory complex I subunits. The young SAMP8 expressed reduced complex I activity, which is controlled by both nuclear and mitochondrial DNA (mtDNA). To exclude the nuclear effects, we isolated transmitochondrial cybrids that share the same nuclear background, but possess mtDNA with or without the mutation. The cybrids showed normal respiratory function irrespective of whether their mtDNA possessed the mutation or not, suggesting that the A11181G mutation is not responsible for respiration defects found in SAMP8.

Kangen-karyu improves memory deficit caused by aging through normalization of neuro-plasticity-related signaling system and VEGF system in the brain

Aim of the study Kangen-karyu (KK) is a traditional Chinese prescription consisting of six different herbs. This study was conducted to investigate the anti-dementia effect of KK on aging-induced cognitive deficits and the underlying mechanism using senescence-accelerated mice prone (SAMP8). Materials and methods Twenty-week old SAMP8 (older SAMP8) were used as an animal model of aging and age-matched senescence-resistant inbred strain (SAMR1) and 8-week-old SAMP8 (young SAMP8) were as controls. Older SAMP8 received daily administration of KK (100 mg/kg, p.o.) or water vehicle for 22 days. Results Compared to the controls, older SAMP8 exhibited cognitive deficits in the object recognition and object location tests; however, KK improved the deficits caused by aging. Moreover, the older SAMP8 treated with vehicle exhibited reduced anxiety-like behavior in the elevated plus-maze test compared to SAMR1, but KK had no effect on emotional disorder of older SAMP8. The levels of biochemical factors related to neuro-plasticity and learning and memory; i.e., phosphorylated forms of N-methyl- d-aspartate receptor 1, Ca 2+/calmodulin-dependent protein kinase II, and cyclic AMP-responsive element-binding protein, and brain-derived neurotrophic factor, were significantly decreased in older SAMP8 compared to those in the control animals. KK normalized the levels of these factors. Moreover, the mRNA and protein levels of vascular endothelial growth factor (VEGF) and its receptor type 2 in the cerebral cortices of older SAMP8 were down-regulated by aging, but these levels were reversed by KK. Conclusions These findings suggest that normalization of neuro-plasticity-related neuronal signaling and VEGF systems in the brain may be of the mechanisms underlying the ameliorative effects of KK on the cognitive deficits in older SAMP8.

Chronic stress induces learning impairment and decreases hippocampal cell proliferation in young adult SAMP8 mice

Chronic stress induces learning impairment and decreases hippocampal cell proliferation in young adult SAMP8 mice

Age-related expression of adenosine receptors in brain from the senescence-accelerated mouse

Senescence-accelerated mice (SAM) are used as a model of aging and age-associated diseases. SAMP8 are prone strains that show shortened life span and deficits in learning and memory processes, while SAMR1 are strains of accelerated senescence-resistant, long-lived mice. Due to their abnormal APP (amyloid precursor protein) metabolism in brain, SAMP8 may be an Alzheimer-type model. Adenosine receptors are G-protein coupled receptors which are altered in brain from Alzheimer disease (AD) cases. The analysis of adenosine receptors in brain from young (21 days old) and middle-aged (180 days old) SAMP8 as compared with SAMR1 mice revealed differences between these strains associated with age. The age-related increase in mRNA coding A 1 and A 2B receptors observed in SAMR1 was absent in SAMP8. A 1 receptors were significantly decreased with age in SAMR1, while no differences were observed in SAMP8. However, the levels of A 1 receptors in young SAMP8 were even lower than those obtained in middle-aged SAMR1. In addition, A 2A receptors were significantly increased only in aged SAMR1. A similar age-related decrease in A 1 receptors level was also observed in brain from male Wistar rats. These results suggest different age-related effects on adenosine receptors in SAMR1 and SAMP8 strains. Since A 1 receptors are mainly neuroprotective, their important loss in very young SAMP8 strain suggests the involvement of these receptors in the pathogenesis of neurodegenerative diseases associated with aging.

Anti-amyloid beta protein antibody passage across the blood–brain barrier in the SAMP8 mouse model of Alzheimer's disease: An age-related selective uptake with reversal of learning impairment

Amyloid beta protein (Aβ) levels are elevated in the brain of Alzheimer's disease patients. Anti-Aβ antibodies can reverse the histologic and cognitive impairments in mice which overexpress Aβ. Passive immunization appears safer than vaccination and treatment of patients will likely require human rather than xenogenic antibodies. Effective treatment will likely require antibody to cross the blood–brain barrier (BBB). Unfortunately, antibodies typically cross the BBB very poorly and accumulate less well in brain than even albumin, a substance nearly totally excluded from the brain. We compared the ability of two anti-Aβ human monoclonal IgM antibodies, L11.3 and HyL5, to cross the BBB of young CD-1 mice to that of young and aged SAMP8 mice. The SAMP8 mouse has a spontaneous mutation that induces an age-related, Aβ-dependent cognitive deficit. There was preferential uptake of intravenously administered L11.3 in comparison to HyL5, albumin, and a control human monoclonal IgM (RF), especially by hippocampus and olfactory bulb in aged SAMP8 mice. Injection of L11.3 into the brains of aged SAMP8 mice reversed both learning and memory impairments in aged SAMP8 mice, whereas IgG and IgM controls were ineffective. Pharmacokinetic analysis predicted that an intravenous dose 1000 times higher than the brain injection dose would reverse cognitive impairments. This predicted intravenous dose reversed the impairment in learning, but not memory, in aged SAMP8 mice. In conclusion, an IgM antibody was produced that crosses the BBB to reverse cognitive impairment in a murine model of Alzheimer's disease.

Accelerated senescence prone mouse-8 shows early onset of deficits in spatial learning and memory in the radial six-arm water maze

Available data indicate that the senescence-accelerated prone mouse 8 (SAMP8) is an appropriate model of brain aging, with impairments in nonspatial learning and memory beginning as early as 2 months of age, and spatial learning and memory deficiencies not becoming apparent until after 4 months of age. However, with other strains (e.g., C57BL mice), the impairment in spatial memory was found earlier than that in nonspatial memory. We considered the possibility that the observed differences could be due to strain-specific differences in the training equipment. In the present study, a new optimized testing apparatus—the radial six-arm water maze (RAWM)—for detecting spatial learning and memory in mice, was employed, to determine whether there is impairment of spatial learning and memory in young SAMP8. The relationship between the spatial learning measures observed with the RAWM and the Morris maze, a classic spatial learning and memory testing apparatus, was also explored. It was found that, in the RAWM, rather than in the Morris maze, the impairment in spatial learning could be measured in SAMP8 mice as early as 3 months old, and the impairment in spatial memory in SAMP8 mice aged 5 months. These results suggested that the spatial learning and memory deficiencies could be found in early life of SAMP8 mice, and that RAWM and Morris maze each detect different aspects of spatial learning and memory.

Accelerated senescence prone mouse-8 shows early onset of deficits in spatial learning and memory in the radial six-arm water maze

Available data indicate that the senescence-accelerated prone mouse 8 (SAMP8) is an appropriate model of brain aging, with impairments in nonspatial learning and memory beginning as early as 2 months of age, and spatial learning and memory deficiencies not becoming apparent until after 4 months of age. However, with other strains (e.g., C57BL mice), the impairment in spatial memory was found earlier than that in nonspatial memory. We considered the possibility that the observed differences could be due to strain-specific differences in the training equipment. In the present study, a new optimized testing apparatus—the radial six-arm water maze (RAWM)—for detecting spatial learning and memory in mice, was employed, to determine whether there is impairment of spatial learning and memory in young SAMP8. The relationship between the spatial learning measures observed with the RAWM and the Morris maze, a classic spatial learning and memory testing apparatus, was also explored. It was found that, in the RAWM, rather than in the Morris maze, the impairment in spatial learning could be measured in SAMP8 mice as early as 3 months old, and the impairment in spatial memory in SAMP8 mice aged 5 months. These results suggested that the spatial learning and memory deficiencies could be found in early life of SAMP8 mice, and that RAWM and Morris maze each detect different aspects of spatial learning and memory.