Impairment In Senescence-accelerated Mouse Prone 8 Mice Research Articles

Molecular hydrogen inhibits neuroinflammation and ameliorates depressive-like behaviors and short-term cognitive impairment in senescence-accelerated mouse prone 8 mice

Background and aimsNeuroinflammation, a low-grade chronic inflammation of the central nervous system, is linked to age-related neuropsychiatric disorders such as senile depression and Alzheimer's disease. Recent studies have explored controlling neuroinflammation as a novel treatment strategy. Molecular hydrogen shows anti-inflammatory effects. However, its impacts on neuroinflammation and age-related neuropsychiatric disorders remain unelucidated. We investigated molecular hydrogen’s effects on microglial activation, neuroinflammation, depressive-like behavior, and short-term cognitive decline in senescence-accelerated mouse-prone 8 (SAMP8) mice. MethodsSix-week-old SAMP8 or senescence-accelerated mouse-resistant 1 (SAMR1) mice received hydrogen-rich jelly (HRJ) or placebo jelly (PJ) from six weeks of age for 26-28 weeks. Depressive-like behavior was assessed using tail suspension and forced swimming tests, while cognitive function was evaluated using the Y-maze and object recognition tests. Brain tissues were used for immunohistochemical studies or to measure pro-inflammatory cytokine levels via enzyme-linked immunosorbent assay (ELISA). ResultsHRJ intake reduced immobility time in both tail suspension and forced swimming tests and enhanced visual cognitive and spatial working memory in SAMP8 mice. Additionally, HRJ intake suppressed the 8-hydroxy-2'-deoxyguanosine (8-OHdG), Iba1, and cleaved caspase 3 expression levels in the medial prefrontal cortex and hippocampal dentate gyrus. Furthermore, HRJ intake significantly lowered IL-6 levels in brain tissues of SAMP8 mice. ConclusionsThese findings suggest that molecular hydrogen treatment may regulate neuroinflammation induced by activated microglia and improve depressive-like behavior and short-term cognitive impairment in SAMP8 mice.

Salidroside alleviates cognitive impairment by inhibiting ferroptosis via activation of the Nrf2/GPX4 axis in SAMP8 mice

BackgroundAlzheimer's disease (AD) is a neurogenerative disease and remains no effective method for stopping its progress. Ferroptosis and adaptive immunity have been proven to contribute to AD pathogenesis. Salidroside exhibits neuroprotective and immunomodulatory effects. However, the underlying mechanisms linking salidroside, ferroptosis, and adaptive immunity in AD remain uncertain. PurposeThe objective of this study is to explore the neuroprotective effects and the potential molecular mechanisms of salidroside against neuronal ferroptosis and CD8+ T cell infiltration in senescence-accelerated mouse prone 8 (SAMP8) mice. Study design and methodsSAMP8 mice were employed as an AD model and were treated with salidroside for 12 weeks. Behavioral tests, immunohistochemistry, HE and Nissl staining, immunofluorescence, transmission electron microscopy, quantitative proteomics, bioinformatic analysis, flow cytometry, iron staining, western blotting, and molecular docking were performed. ResultsTreatment with salidroside dose-dependently attenuated cognitive impairment, reduced the accumulation of Aβ plaques and restored neuronal damage. Salidroside also suppressed the infiltration of CD8+T cells, oxidative stress, and inflammatory cytokines, and improved mitochondrial metabolism, iron metabolism, lipid metabolism, and redox in the SAMP8 mice brain. The administration of salidroside decreased iron deposition, reduced TFR1, and ACSL4 protein expression, upregulated SLC7A11, and GPX4 protein expression, and promoted the Nrf2/GPX4 axis activation. ConclusionIn conclusion, neuronal ferroptosis and CD8+T cells are involved in the process of cognitive impairment in SAMP8 mice. Salidroside alleviates cognitive impairment and inhibits neuronal ferroptosis. The underlying mechanisms may involve the Nrf2/GPX4 axis activation and reduction in CD8+T cells infiltration. This study provides some evidence for the roles of salidroside in adaptive immunity and neuronal ferroptosis in SAMP8 mice.

Effects of Scrophularia buergeriana Extract (Brainon®) on Aging-Induced Memory Impairment in SAMP8 Mice

Alzheimer's disease (AD) is a worldwide problem. Currently, there are no effective drugs for AD treatment. Scrophularia buergeriana Miquel (SB) is a traditional herbal medicine used in Korea to treat various diseases. Our previous studies have shown that ethanol extract of SB roots (SBE, Brainon®) exhibits potent anti-amnesic effects in Aβ1-42- or scopolamine-treated memory impairment mice model and neuroprotective effects in a glutamate-induced SH-SY5Y cell model. In this study, we evaluated the therapeutic effects of Brainon® and its mechanism of action in senescence-accelerated mouse prone 8 (SAMP8) mice. Brainon® (30 or 100 mg/kg/day) was orally treated to six-month-old SAMP8 mice for 12 weeks. Results revealed that Brainon® administration effectually ameliorated cognitive deficits in Y-maze and passive avoidance tests. Following the completion of behavioral testing, western blotting was performed using the cerebral cortex. Results revealed that Brainon® suppressed Aβ1-42 accumulation, Tau hyperphosphorylation, oxidative stress, and inflammation and alleviated apoptosis in SAMP8 mice. Brainon® also promoted synaptic function by downregulating the expression of AChE and upregulating the expression of p-CREB/CREB and BDNF. Furthermore, Brainon® restored SAMP8-reduced expression of ChAT and -dephosphorylated of ERK and also decreased AChE expression in the hippocampus. Furthermore, Brainon® alleviated AD progression by promoting mitophagy/autophagy to maintain normal cellular function as a novel finding of this study. Our data suggest that Brainon® can remarkably improve cognitive deficiency with the potential to be utilized in functional food for improving brain health.

Tooth loss early in life induces hippocampal morphology remodeling in senescence-accelerated mouse prone 8 (SAMP8) mice.

Long-term tooth loss is associated with the suppression of hippocampal neurogenesis and impairment of hippocampus-dependent cognition with aging. The morphologic basis of the hippocampal alterations, however, remains unclear. In the present study, we investigated whether tooth loss early in life affects the hippocampal ultrastructure in senescence-accelerated mouse prone 8 (SAMP8) mice, using transmission electron microscopy. Male SAMP8 mice were randomized into control or tooth-loss groups. All maxillary molar teeth were removed at 1 month of age. Hippocampal morphologic alterations were evaluated at 9 months of age. Tooth loss early in life induced mitochondrial damage and lipofuscin accumulation in the hippocampal neurons. A thinner myelin sheath and decreased postsynaptic density length were also observed. Our results revealed that tooth loss early in life may lead to hippocampal ultrastructure remodeling and subsequent hippocampus-dependent cognitive impairment in SAMP8 mice with aging.

Integration of transcriptomics and network analysis deciphers the mechanisms of baicalein in improving learning and memory impairment in senescence-accelerated mouse prone 8 (SAMP8)

Our previous work suggested that baicalein could delay senescence and improve cognitive dysfunction in senescence-accelerated mouse prone 8 (SAMP8). Although baicalein has shown therapeutical benefits in improving learning and memory impairment, the exact molecular mechanisms have not been fully understood. In the present work, transcriptomics was integrated with gene network analysis for revealing the potential mechanisms of baicalein in improving learning and memory in SAMP8 mice. The results showed that baicalein regulated fifty hub differently expressed genes (DEGs) that were enriched in eight signaling pathways. Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway was especially significant among them, therefore, the DEGs (Gh1, Il5, Il7, Il20rb, Prlr and Socs1) in JAK-STAT signaling pathway were verified by quantitative real-time PCR, and the key proteins (JAK2, p-JAK2, STAT1 and p-STAT1) and related proteins including β-amyloid peptide (Aβ1-42) and receptor for advanced glycation end products (RAGE) were assayed by Western blot and enzyme-linked immunosorbent assay. Our results suggest that baicalein prevented the activation of JAK2/STAT1 signaling pathway and decreased the levels of Aβ1-42 and RAGE in the cortex of SAMP8 mice. Taken together, our study unmasks the mechanism of baicalein on improving learning and memory impairment in SAMP8 mice, which is dependent upon the inhibition of Aβ1-42 and RAGE/JAK2/STAT1 cascade.

Yokukansan Ameliorates Hippocampus-Dependent Learning Impairment in Senescence-Accelerated Mouse.

Yokukansan (YKS) is a traditional Japanese herbal medicine. It has been currently applied for treating behavioral and psychological symptoms of dementia in Japan. We investigated the effect of YKS on learning ability, hippocampal cell proliferation, and neural ultrastructural features in senescence-accelerated mouse prone 8 (SAMP8), a proposed animal model of Alzheimer's disease. Five-month-old male SAMP8 mice were randomly assigned to control and experimental groups. The control group had drug-free water ad libitum. The experimental mice were given 0.15% aqueous solution of YKS orally for eight weeks. Learning ability was assessed in Morris water maze test. Hippocampal cell proliferation was investigated using bromodeoxyuridine immunohistochemical method. The neural ultrastructural features, including myelin sheath and synapse, were investigated electron microscopy. Administration with YKS improved the hippocampal cell proliferation in dentate gyrus, and ameliorated learning impairment in SAMP8 mice. Numerous lipofuscin inclusions were presented in hippocampal neurons of the control mice. However, little were found after treatment with YKS. Myelin sheath was thicker and postsynaptic density length was longer after treatment with YKS. Administration with YKS ameliorated learning impairment in SAMP8 mice, mediated at least partially via delaying neuronal aging process, neurogenesis, myelin sheath and synaptic plasticity in the hippocampus. These results suggest that YKS might be effective for preventing hippocampus-dependent cognitive deficits with age.

Chia Seed Does Not Improve Cognitive Impairment in SAMP8 Mice Fed with High Fat Diet

Background: Chia seed is an ancient seed with the richest plant source of α-linolenic acid, which has been demonstrated to improve metabolic syndrome associated risk factors. Under high fat diet (HFD) condition, the senescence-accelerated mouse-prone 8 (SAMP8) mice demonstrated worsen Alzheimer’s disease (AD) related pathology compared to low fat diet fed SAMP8 mice. Objective: To explore whether chia seed supplementation might improve cognitive impairment under aging and metabolic stress via high fat diet (HFD) fed SAMP8 mice as a model. Design: SAMP8 mice and senescence-accelerated mouse-resistant 1 (SAMR1) were randomized into 4 groups, i.e., SAMR1 low fat diet group (SAMR1-LFD), SAMP8-HFD and SAMP8-HFD group supplemented with 10% chia seed (SAMP8-HFD+Chia). At the end of the intervention, cognitive function was measured via Morris water maze (MWM) test. Hippocampus and parietal cortex were dissected for further analysis to measure key markers involved AD pathology including Aβ, tau and neuro-inflammation. Results: During navigation trials of MWM test, mice in SAMP8-LFD group demonstrated impaired learning ability compared to SAMR1-LFD group, and chia seed had no effect on learning and memory ability for HFD fed SAMP8 mice. As for Alzheimer’s disease (AD) related pathology, chia seed not only increased α-secretase such as ADAM10 and insulin degrading enzyme (IDE), but also increased β-secretase including beta-secretase 1 (BACE1) and cathepsin B, with an overall effects of elevation in the hippocampal Aβ42 level; chia seed slightly reduced p-Tauser404 in the hippocampus; while an elevation in neuro-inflammation with the activation of glial fibrillary acidic protein (GFAP) and Ibα-1 were observed post chia seed supplementation. Conclusions: Chia seed supplementation did not improve cognitive impairment via MWM in HFD fed SAMP8 mice. This might be associated with that chia seed increased key enzymes involved both in non-amyloidogenic and amyloidogenic pathways, and neuro-inflammation. Future studies are necessary to confirm our present study.

Long-Term DL-3-n-Butylphthalide Treatment Alleviates Cognitive Impairment Correlate With Improving Synaptic Plasticity in SAMP8 Mice.

Alzheimer’s disease (AD) is the most prevalent form of dementia worldwide. AD is characterized by mild cognitive impairment at onset, irreversibly progressing with age to severe neurodegeneration and cognitive deficits in the late stages. Unfortunately, no effective treatments exist to prevent or delay the cognitive symptoms of AD. Studies have shown that DL-3-n-butylphthalide (DL-NBP) alleviates cognitive impairment induced by amyloid-β in mice by reducing oxidative stress, inhibiting apoptosis, and decreasing tau phosphorylation. In this study, we examined the effects of DL-NBP administration on cognitive function in the senescence-accelerated mouse prone 8 (SAMP8) model of age-related dementia. DL-NBP treatment for 3 months alleviated cognitive impairment in SAMP8 mice as assessed by performance in the Morris water maze test. Moreover, DL-NBP significantly increased the expression of synaptophysin and postsynaptic density protein 95 in the hippocampus of SAMP8 mice, indicative of a protective effect on hippocampal structural synaptic plasticity. In addition, brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling, previously shown to promote synaptic plasticity, was significantly enhanced by the DL-NBP administration. Our findings suggest that DL-NBP is a potential drug candidate for the treatment of cognitive impairment in AD and may serve as the foundation for further research into the development of AD drugs.

Effects of Bushen-Yizhi formula on age-related inflammation and oxidative stress in senescence-accelerated mice.

The present study aimed to investigate the possible effects and underlying molecular mechanism of Bushen-Yizhi formula (BSYZ), a traditional Chinese medicine, on age-related degeneration of brain physiology in senescence-accelerated mouse prone 8 (SAMP8) mice. SAMP8 mice (age, 6 months) were administered BSYZ (1.46, 2.92 and 5.84 g/kg/day) for 30 days. Morris water maze and step-down tests demonstrated that BSYZ significantly improved memory impairments in SAMP8 mice. In addition, BSYZ significantly enhanced the expression levels of peroxisome proliferator-activated receptor-γ and B-cell lymphoma extra-large, and downregulated the expression levels of inflammatory mediators, glial fibrillary acidic protein, cyclooxygenase-2, nuclear factor-κB and interleukin-1β in the brain compared with untreated SAMP8 mice. Furthermore, BSYZ reversed disordered superoxide dismutase activity, malondialdehyde content and glutathione peroxidase activity, and ameliorated apoptosis and histological alterations. The present study indicated that BSYZ may attenuate cognitive impairment in SAMP8 mice, and modulate inflammation, oxidative stress and neuronal apoptosis. These results suggested that BSYZ may have the potential to be further developed into a therapeutic agent for protection against age-related neurodegenerative diseases.

Downregulated Nuclear Factor E2-Related Factor 2 (Nrf2) Aggravates Cognitive Impairments via Neuroinflammation and Synaptic Plasticity in the Senescence-Accelerated Mouse Prone 8 (SAMP8) Mouse: A Model of Accelerated Senescence.

BackgroundWe observed the effects of nuclear factor E2-related factor 2 (Nrf2) downregulation via intrahippocampal injection of a lentiviral vector on cognition in senescence-accelerated mouse prone 8 (SAMP8) to investigate the role of the (Nrf2)/antioxidant response element (ARE) pathway in age-related changes.Material/MethodsControl lentivirus and Nrf2-shRNA-lentivirus were separately injected into the hippocampus of 4-month-old SAMR1 and SAMP8 mice and then successfully downregulated Nrf2 expression in this brain region. Five months later, cognitive function tests, including the novel object test, the Morris water maze test, and the passive avoidance task were conducted. Glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba1) immunohistochemistry was performed to observe an inflammatory response. Presynaptic synapsin (SYN) were observed by immunofluorescence. We then determined the Nrf2-regulated, heme oxygenase-1 (HO-1), P65, postsynaptic density protein (PSD), and SYN protein levels. The ultrastructure of neurons and synapses in the hippocampal CA1 region was observed by transmission electron microscopy.ResultsAging led to a decline in cognitive function compared with SAMR1 mice and the Nrf2-shRNA-lentivirus further exacerbated the cognitive impairment in SAMP8 mice. Nrf2, HO-1, PSD, and SYN levels were significantly reduced (all P<0.05) but high levels of inflammation were detected in SAMP8 mice with low expression of Nrf2. Furthermore, neurons were vacuolated, the number of organelles decreased, and the number of synapses decreased.ConclusionsDownregulation of Nrf2 suppressed the Nrf2/ARE pathway, activated oxidative stress and neuroinflammation, and accelerated cognitive impairment in SAMP8 mice. Downregulation of Nrf2 accelerates the aging process through neuroinflammation and synaptic plasticity.

The Effects of LW-AFC on the Hippocampal Transcriptome in Senescence-Accelerated Mouse Prone 8 Strain, a Mouse Model of Alzheimer's Disease.

The senescence-accelerated mouse prone 8 (SAMP8) strain is considered a robust experimental model for developing preventative and therapeutic treatments for Alzheimer's disease (AD), a neurodegenerative disease which cannot be effectively prevented, halted, or cured. Our previous studies showed that LW-AFC, a new formula derived from the classical traditional Chinese medicinal prescription Liuwei Dihuang decoction, ameliorates cognitive deterioration in PrP-hAβPPswe/PS1ΔE9 transgenic mice and SAMP8 mice. This study aims to investigate the mechanism that mediates how LW-AFC improves cognitive deficit on the basis of the transcriptome. We conducted a genome-wide survey of gene expression in the hippocampus in mice from the senescence accelerated mouse resistant 1 (SAMR1) strain, from SAMP8 and from LW-AFC treated SAMP8. The results showed that LW-AFC reversed the transcriptome in the hippocampus of SAMP8 mice. The specific investigation of altered gene expression in subtypes defined by cognitive profiles indicated that the systemic lupus erythematosus pathway, spliceosomes, amyotrophic lateral sclerosis, and the insulin signaling were involved in the improvement of cognitive ability by LW-AFC. The expression of genes Enpp2, Etnk1, Epdr1, and Gm5900 in the hippocampus were correlated with that of LW-AFC's ameliorating cognitive impairment in SAMP8 mice. Because LW-AFC is composed of polysaccharides, glycosides, and oligosaccharides, we infer that LW-AFC has direct or indirect effects on altering gene expressions and regulating pathways in the hippocampus of SAMP8 mice. These data are helpful for the enhanced identification of LW-AFC as new therapeutic modalities to AD.

Effects of enriched environment on cognitive situation in senescence accelerated mouse prone/8 with mild cognitive impairment

Objective To investigate the effects of enriched environment on cognitive situation in senescence accelerated mouse prone/8(SAMP8) with mild cognitive impairment (MCI) and the possible regulatory mechanisms. Methods A total of 20 healthy male SAMP8 mice in MCI (5-month-old) were randomly divided into enriched environment group (short for P8 EE group) and standard environment group (short for P8 SE group) with 10 in each group. Two groups of SAMP8 mice were subjected to the two different environments for 60 days. 10 5-month-old healthy male SAMR1 mice were selected as normal control group (short for R1 SE group) and subjected to the standard environment for 60 days. The cognitive situation of mice in each group before and after intervention was examined by the Morris water maze (MWM) test. The deposition of amyloid protein beta(Aβ) and expression of glial fibrillary acidic protein(GFAP) in hippocampal CA1 of mice in each group after intervention were determined by immunohistochemical staining and image analysis system. Results In the MWM test, there were statistical differences of latency and times of crossing the platform before and after intervention in each group(all P<0.05). The average latency ((81.22±11.82)s, (76.59±13.36)s, (70.74±8.73)s, (66.40±7.79)s) of P8 EE group after intervention were significantly shorter than that of P8 SE group on four consecutive days (P<0.01), while the times of crossing platform in P8 EE group after intervention (9.31±1.33) were more than that in P8 SE group after intervention (P<0.01). There were significant differences of escape latency and crossing times between P8 EE group and R1 SE group after intervention (all P<0.01). By immunohistochemical staining, the average absorbance of Aβ and GFAP((0.26±0.02), (0.26±0.03)) in P8 EE group after intervention were significantly less than that in P8 SE group after intervention (P<0.01). There were significant differences of Aβ and GFAP levels between P8 EE group and R1 SE group after intervention (both P<0.01). Conclusion Enriched environment can reduce cognitive impairment in SAMP8 mice with mild cognitive impairment, which may be associated with restraining the deposition of Aβ in hippocampus, reducing the expression of GFAP and inhibiting the activation of AST. Key words: Enriched environment; Learning and memory; Amyloid protein beta; Glial fibrillary acidic protein; Mild cognitive impairment

Age-Related Alterations in the Metabolic Profile in the Hippocampus of the Senescence-Accelerated Mouse Prone 8: A Spontaneous Alzheimer's Disease Mouse Model

Alzheimer's disease (AD), the most common age-dependent neurodegenerative disorder, produces a progressive decline in cognitive function. The metabolic mechanism of AD has emerged in recent years. In this study, we used multivariate analyses of gas chromatography-mass spectrometry measurements to determine that learning and retention-related metabolic profiles are altered during aging in the hippocampus of the senescence-accelerated mouse prone 8 (SAMP8). Alterations in 17 metabolites were detected in mature and aged mice compared to young mice (13 decreased and 4 increased metabolites), including metabolites related to dysfunctional lipid metabolism (significantly increased cholesterol, oleic acid, and phosphoglyceride levels), decreased amino acid (alanine, serine, glycine, aspartic acid, glutamate, and gamma-aminobutyric acid), and energy-related metabolite levels (malic acid, butanedioic acid, fumaric acid, and citric acid), and other altered metabolites (increased N-acetyl-aspartic acid and decreased pyroglutamic acid, urea, and lactic acid) in the hippocampus. All of these alterations indicated that the metabolic mechanisms of age-related cognitive impairment in SAMP8 mice were related to multiple pathways and networks. Lipid metabolism, especially cholesterol metabolism, appears to play a distinct role in the hippocampus in AD.

Oligomerised lychee fruit-derived polyphenol attenuates cognitive impairment in senescence-accelerated mice and endoplasmic reticulum stress in neuronal cells

Recently, the ability of polyphenols to reduce the risk of dementia and Alzheimer's disease (AD) has attracted a great deal of interest. In the present study, we investigated the attenuating effects of oligomerised lychee fruit-derived polyphenol (OLFP, also called Oligonol) on early cognitive impairment. Male senescence-accelerated mouse prone 8 (SAMP8) mice (4 months old) were given OLFP (100 mg/kg per d) for 2 months, and then conditioned fear memory testing was conducted. Contextual fear memory, which is considered hippocampus-dependent memory, was significantly impaired in SAMP8 mice compared with non-senescence-accelerated mice. OLFP attenuated cognitive impairment in SAMP8 mice. Moreover, the results of real-time PCR analysis that followed DNA array analysis in the hippocampus revealed that, compared with SAMP8 mice, the mRNA expression of Wolfram syndrome 1 (Wfs1) was significantly higher in SAMP8 mice administered with OLFP. Wfs1 reportedly helps to protect against endoplasmic reticulum (ER) stress, which is thought to be one of the causes for AD. The expression of Wfs1 was significantly up-regulated in NG108-15 neuronal cells by the treatment with OLFP, and the up-regulation was inhibited by the treatment of the cells with a c-Jun N-terminal kinase-specific inhibitor rather than with an extracellular signal-regulated kinase inhibitor. Moreover, OLFP significantly attenuated the tunicamycin-induced expression of the ER stress marker BiP (immunoglobulin heavy chain-binding protein) in the cells. These results suggest that OLFP has an attenuating effect on early cognitive impairment in SAMP8 mice, and diminishes ER stress in neuronal cells.

Involvement of leucine zipper transcription factor-like protein 1 (Lztfl1) in the attenuation of cognitive impairment by exercise training

It is well known that exercise prevents and reduces cognitive impairment. In the present study, we focused on exercise training as a tool to prevent cognitive impairment, and searched for novel molecules that may relate to the prevention of cognitive impairment in the hippocampus. Two-month-old senescence-accelerated mouse prone-8 (SAMP8) mice were subjected to voluntary exercise training by running on a wheel for 4 months, and were then assigned a conditioned fear memory test. Moreover, various mRNA levels in the hippocampus were examined by DNA array analysis and real-time PCR. Contextual fear memory in SAMP8 control mice was significantly impaired compared with that in non-senescence mice. Exercise training definitely attenuated such cognitive impairment. The results of real-time PCR analysis that was conducted following DNA array analysis in the hippocampus revealed that, compared with SAMR8 control mice, the expression levels of leucine zipper transcription factor-like protein 1 (Lztfl1) mRNA were significantly higher in SAMP8 mice subjected to exercise training. In addition, the overexpression of Lztfl1 promoted neurite outgrowth in Neuro 2a cells. These results suggest that exercise has a preventive effect on cognitive impairment in SAMP8 mice, and that exercise-induced increase in Lztfl1 induces neurite outgrowth.

JD-30, an active fraction extracted from Danggui–Shaoyao–San, decreases β-amyloid content and deposition, improves LTP reduction and prevents spatial cognition impairment in SAMP8 mice

JD-30 is an active fraction extracted from Danggui–Shaoyao–San (DSS), a traditional Chinese medicinal prescription. We previously showed that JD-30 could alleviate cognitive dysfunction of the mice induced by intracerebroventricular injection of β-amyloid (Aβ). However, data remain scarce on the effect of JD-30 on an Alzheimer's disease (AD) model and the underlying mechanisms are unknown. Further detailed studies on the effects of JD-30 on spatial cognition of senescence-accelerated mouse prone 8 (SAMP8), a suitable rodent model for cognitive impairment of aged subjects were investigated to elucidate the possible mechanisms. Long-term treatment with JD-30 significantly decreased the prolonged latency of SAMP8 in the Morris water-maze test. It also ameliorated the reduction of long-term potentiation (LTP) and reduced the damage of neurons in the hippocampus of SAMP8. Finally, JD-30 decreased the content and deposition of Aβ in the brain of SAMP8. The results show that JD-30 improves deterioration of spatial learning and memory in the SAMP8 mouse model, and by decreasing the content and deposition of Aβ, neuronal activity and synaptic plasticity improve, suggesting one of the mechanisms involved.