Neurochemistry, Neuropathology, and Heredity in SAMP8: A Mouse Model of Senescence

Takano, Koji; Nomura, Yasuyuki

doi:10.1007/s11064-009-9923-x

Cited by 77 publications

(58 citation statements)

References 95 publications

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“…One of these substrains, the senescenceaccelerated mouse prone-8 (SAMP8) strain manifests irreversible advancing senescence and shares similar characteristics with aged humans such as a reduced lifespan, lordosis, hair loss, and reduced physical activity (Hamamoto et al, 1984;Takeda et al, 1994), whereas the senescence-accelerated mice resistant-1 (SAMR1) strain presents a normal ageing pattern (Takeda, 1999). Interestingly, SAMP8 mice also exhibit age-related learning and memory deficits, as well as amyloid-like deposits in the brain (Del Valle et al, 2010;Tomobe and Nomura, 2009) and increased expression of hyperphosphorylated Tau (Canudas et al, 2005;Orejana et al, 2012). Given such features, SAMP8 mice have been proposed as suitable rodent model for studying age-associated pathologies (Tomobe and Nomura, 2009), or even as an AD animal model (Liu et al, 2010;Pallas et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Propranolol restores cognitive deficits and improves amyloid and Tau pathologies in a senescence-accelerated mouse model

et al. 2013

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Section: Introductionmentioning

confidence: 99%

Propranolol restores cognitive deficits and improves amyloid and Tau pathologies in a senescence-accelerated mouse model

et al. 2013

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“…5 A variety of neuropathological defects of SAMP8 have been documented, such as the deposition of Aβ, hyperphosphorylation of tau, impaired development of dendritic spines and sponge formation. [6][7][8] Neuron loss in the hippocampus is related to memory impairment, [9][10][11][12] but little attention has been paid to the neuron density of the hippocampus of SAMP8 mice.…”

Section: Introductionmentioning

confidence: 99%

Acupuncture Improves Cognitive Deficits and Increases Neuron Density of the Hippocampus in Middle-Aged Samp8 Mice

Zhang

Cheng

et al. 2012

Acupunct Med

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Objectives To examine whether acupuncture could improve cognitive deficits and reduce the loss of neurons in mice models of ageing. Methods Male 7.5-month-old senescenceaccelerated mouse prone 8 (SAMP8) and age-matched senescence-resistant inbred strains 1 (SAMR1) were divided into four groups (n=15 per group): SAMP8 acupuncture group (Pa), SAMP8 non-acupuncture point control group (Pn), SAMP8 control group (Pc) and SAMR1 normal control group (Rc). The behaviours were examined by the Morris water maze test and the neuron density in the hippocampus was estimated by the optical fractionator technique. Results The Morris water maze test demonstrated that the cognitive deficits of SAMP8 mice were improved by acupuncture treatment. Neuronal loss was found in hippocampal regions CA1 (−24%), CA3 (−18%) and DG (−28%) of Pc compared with Rc. The neuron number in hippocampal CA3 and DG of the Pa group was significantly increased by therapeutic acupuncture compared with the Pc group. Conclusions Acupuncture improved the cognitive impairment of middle-aged SAMP8 mice which could be attributed to the reduced neuron loss in hippocampal regions CA3 and DG. These results suggest that reducing neuron loss in the hippocampus by acupuncture is a potential therapeutic approach for the treatment of Alzheimer's disease and cognitive impairment diseases. INTRODUCTIONThe senescence-prone inbred strains senescence-accelerated mouse prone (SAMP) and senescence-resistant inbred strains (SAMR) are important mouse models of ageing.

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“…The unique characteristic of SAMP8 mice is that it has a low incidence of other phenotypic aging alterations when its deficits in learning and memory are developed. SAMP8 mice have been considered by many investigators as a useful model for age-dependent neurodegeneration and senescence [7][8][9][10][11] . Moreover, zinc is a potent inhibitor of caspase-3 12 , a protein critical for apoptotic cell death.…”

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confidence: 99%

Metallothionein 3 attenuated the apoptosis of neurons in the CA1 region of the hippocampus in the senescence-accelerated mouse/PRONE8 (SAMP8)

Wang

Chen

et al. 2011

Arq. Neuro-Psiquiatr.

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Objective: Metallothionein 3 (MT-3) has been shown to protect against apoptotic neuronal death in the brains of patients with Alzheimer's disease. Zinc is a potent inhibitor of caspase-3 and its deficiency was found to promote apoptosis. Here, we measured the zinc and copper content in the brains of senescence-accelerated mouse/PRONE8 (SAMP8) and sought to investigate the effect of MT-3 on the apoptosis of neurons in the hippocampal CA1 region of these mice. Method: The zinc and copper content in the brain samples of SAMP8 and normal control SAMR1 mice were determined using an atomic absorption spectrophotometer. The mice were administered intraperitoneally for four weeks with MT-3 or MT1 and thereafter apoptosis was measured using the TUNEL method and the expression of anti-apoptotic protein Bcl-2 and proapoptotic protein Bax was examined by immunohistochemistry. Results: Compared with that in SMAR1 mice, the content of zinc in the brains of SAMP8 mice was significantly reduced (P<0.05). Moreover, significant levels of apoptosis of neurons were observed in the hippocampus of SAMP8 mice, which, compared with those in SMAR1 mice, also showed significantly lower levels of Bcl-2 and higher levels of Bax (P<0.05). MT-3 increased zinc concentration in the hippocampus of SAMP8 mice and also significantly decreased apoptosis in these neurons dose-dependently and increased the levels of Bcl-2 and decreased the levels of Bax. Conclusion: MT-3 could attenuate apoptotic neuron death in the hippocampus of SAMP8, suggesting that the protein may lessen the development of neurodegeneration. Key words: metallothionein 3 (MT-3), SAMP8, neurodegeneration, apoptosis.Metalotioneina 3 atenuou a apoptose dos neurônios da região CA1 do hipocampo em camundongos PRONE8 com envelhecimento acelerado (SAMP8) RESUMO Objetivo: Metalotioneína 3 (MT-3) tem mostrado proteção contra a apoptose neuronal em cérebros de pacientes com doença de Alzheimer. Zinco é um potente inibidor da caspase-3, e sua deficiência pode promover a apoptose. No presente trabalho, foram dosados os níveis de zinco e cobre nos cérebros de camundongos PRONE8 com envelhecimento acelerado (SAMP8), visando investigar o efeito da MT-3 na apoptse dos neurônios da região hipocampal CA1 destes camundongos. Método: Os níveis de zinco e cobre em amostras cerebrais de camundongos SAMP8 e de controles normais SAMR1 foram determinados por absorção atômica em espectrofotometria. Foram administradas MT-3 ou MT-1 intraperitoneais durante quatro semanas, sendo em seguida avaliada a apoptose pelo método TUNEL , enquanto a expressão da proteína anti-apoptótica Bcl-2 e a proteína pró-apoptótica Bax foram avaliadas por imunohistoquímica. Resultados: Em comparação aos camundongos SMAR1, o nível de zinco nas amostras cerebrais dos Correspondence Haixiong Xu

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Neurochemistry, Neuropathology, and Heredity in SAMP8: A Mouse Model of Senescence

Cited by 77 publications

References 95 publications

Propranolol restores cognitive deficits and improves amyloid and Tau pathologies in a senescence-accelerated mouse model

Propranolol restores cognitive deficits and improves amyloid and Tau pathologies in a senescence-accelerated mouse model

Acupuncture Improves Cognitive Deficits and Increases Neuron Density of the Hippocampus in Middle-Aged Samp8 Mice

Metallothionein 3 attenuated the apoptosis of neurons in the CA1 region of the hippocampus in the senescence-accelerated mouse/PRONE8 (SAMP8)

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