Senescence-Accelerated Mouse (SAM) with Special References to Neurodegeneration Models, SAMP8 and SAMP10 Mice

Abstract

The SAM strains, a group of related inbred strains consisting of senescence-prone inbred strains (SAMP) and senescence-resistant inbred strains (SAMR), have been successfully developed by selective inbreeding of the AKR/J strain of mice donated by the Jackson laboratory in 1968. The characteristic feature of aging common to the SAMP and SAMR is accelerated senescence and normal aging, respectively. Furthermore, SAMP and SAMR strains of mice manifest various pathobiological phenotypes spontaneously. Among SAMP strains, SAMP8 and SAMP10 mice show age-related behavioral deterioration such as deficits in learning and memory, emotional disorders (reduced anxiety-like behavior and depressive behavior) and altered circadian rhythm associated with certain pathological, biochemical and pharmacological changes. Here, the previous and recent literature on SAM mice are reviewed with an emphasis on SAMP8 and SAMP10 mice. A spontaneous model like SAM with distinct advantages over the gene-modified model is hoped by investigators to be used more widely as a biogerontological resource to explore the etiopathogenesis of accelerated senescence and neurodegenerative disorders.

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

“…MT-3 reduced apoptosis of neurons in the CA1 region of the hippocampus in a dosedependent manner in SAMP8 mice Zn deficiency has been shown to induce apoptosis in neuronal cells 6 and we examined whether low zinc content in the hippocampus of SAMP8 mice was associated with apoptosis of neurons in the CA1 region and the effect of MT-3 on the apoptotic cell death of neurons in the hippocampus using the TUNEL method and found that minimal apoptosis of neurons (5.6±1.1%) was observed in the CA1 region of the hippocampus in normal control mice SAMR1 (Fig 1A). By contrast, we detected massive apoptosis of neurons in the hippocampus CA1 region (38.8±3.1%) in the dementia group (Fig 1B).…”

“…Senescence-accelerated mouse/PRONE 8 (SAMP8) developed by Takeda et al show age-related behavioral deterioration such as deficits in learning and memory and emotional disorders and have an average lifespan of 12.1 months 6 . These mice have been widely used by investigators to explore the etiopathogenesis of accelerated senescence and neurodegenerative disorders while senes-China.…”

Cognitive-enhancing effects of hydrolysate of polygalasaponin in SAMP8 mice

“…Besides this, SAMP8 mice show neuroenergetic imbalances including a decrease in mitochondrial glutathione (GSH) content, Mn-superoxide dismutase (MnSOD), Cu/Zn-SOD, catalase activity, complex IV activity, and adenosine-5'-triphosphate (ATP) levels (Xu et al, 2007;Shi et al, 2010). On the other hand, senescenceaccelerated resistant mouse 1 (SAMR1) of normal aging exhibits no senescence-related neuronal phenotypes and has a genetic background similar to that of SAMP8; it has been used extensively as a control (Takeda, 2009;Bayod et al, 2015).…”

Presence of a neo-epitope and absence of amyloid beta and tau protein in degenerative hippocampal granules of aged mice

“…These animals exhibit early onset and irreversible advance of senescence, as demonstrated by the loss of normal behaviour, the appearance of skin lesions, increased lordokyphosis and a shortened lifespan (Takeda, 2009). Moreover, the SAMP8 strain manifests learning and memory deficits (Miyamoto 1997), neuronal cell loss (Kawamata et al 1997), gliosis (Nomura and Okuma 1999), a reduction in the release of neurotransmitters in the brain (Kitamura et al 1992) and increased oxidative stress (Zhang et al 2008).…”