Silibinin Alleviates the Learning and Memory Defects in Overtrained Rats Accompanying Reduced Neuronal Apoptosis and Senescence

Liu, Bo; Liu, Weiwei; Liu, Panwen; Liu, Xiumin; Song, Xiao-Yu; Hayashi, Toshihiko; Onodera, Satoshi; Ikejima, Takashi

doi:10.1007/s11064-019-02816-2

Cited by 32 publications

(13 citation statements)

References 62 publications

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“…Moreover, long‐term forced treadmill running showed contradictory effects on the markers of senescent cells, including p16 INK4a , p21 Cip1 , and SA‐β‐Gal (Bao et al, 2020; Jang et al, 2019; Wong et al, 2019; Yoon et al, 2019; Zhang et al, 2016), although four out of five studies showed senolytic effects of exercise in specific tissues under obesity or aging conditions. Conversely, studies on an acute bout of downhill running and prolonged swimming reported an increased level of p21 Cip1 and SA‐β‐Gal in fibro/adipogenic progenitors (Saito et al, 2020), and liver and brain (Huang et al, 2013; Liu et al, 2019), respectively, while another swimming study indicated a reduced level of SA‐β‐Gal in the muscle (Fan et al, 2017). In summary, 10 out of 13 animal studies showed a senolytic effect of exercise, but this effect was influenced by the form and dosage of exercise, type of senescent tissue or cells, and healthy or aging/disease conditions.…”

Section: Resultsmentioning

confidence: 99%

Is exercise a senolytic medicine? A systematic review

Chen

Wong

et al. 2020

Aging Cell

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Cellular senescence, a state of irreversible growth arrest triggered by various stressors, engages in a category of pathological processes, whereby senescent cells accumulate in mitotic tissues. Senolytics as novel medicine against aging and various diseases through the elimination of senescent cells has emerged rapidly in recent years. Exercise is a potent anti‐aging and anti‐chronic disease medicine, which has shown the capacity to lower the markers of cellular senescence over the past decade. However, whether exercise is a senolytic medicine for aging and various diseases remains unclear. Here, we have conducted a systematic review of the published literature studying the senolytic effects of exercise or physical activity on senescent cells under various states in both human and animal models. Exercise can reduce the markers of senescent cells in healthy humans, while it lowered the markers of senescent cells in obese but not healthy animals. The discrepancy between human and animal studies may be due to the relatively small volume of research and the variations in markers of senescent cells, types of cells/tissues, and health conditions. These findings suggest that exercise has senolytic properties under certain conditions, which warrant further investigations.

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Section: Resultsmentioning

confidence: 99%

Is exercise a senolytic medicine? A systematic review

Chen

Wong

et al. 2020

Aging Cell

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“…It hydrolyzes β-galactosides to monosaccharides and the enzyme is active even at acidic pH (6.0). SA-β-gal activity has been widely used as a reliable marker of cellular senescence in brain (20)(21)(22) and other organs (23,24). In the present study, using an advanced blast simulator (ABS) to expose animals to single and tightly coupled repeated blasts, we have carried out postmortem evaluation of SA-β-gal activity in different anatomical regions of the brain at various time points up to 1 year post-blast exposures to determine whether blast exposure accelerate cellular senescence, an indicator of aging processes.…”

Section: Introductionmentioning

confidence: 99%

Blast Exposure Leads to Accelerated Cellular Senescence in the Rat Brain

et al. 2020

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Blast-induced traumatic brain injury (bTBI) is one of the major causes of persistent disabilities in Service Members, and a history of bTBI has been identified as a primary risk factor for developing age-associated neurodegenerative diseases. Clinical observations of several military blast casualties have revealed a rapid age-related loss of white matter integrity in the brain. In the present study, we have tested the effect of single and tightly coupled repeated blasts on cellular senescence in the rat brain. Isoflurane-anesthetized rats were exposed to either a single or 2 closely coupled blasts in an advanced blast simulator. Rats were euthanized and brains were collected at 24 h, 1 month and 1 year post-blast to determine senescence-associated-β-galactosidase (SA-β-gal) activity in the cells using senescence marker stain. Single and repeated blast exposures resulted in significantly increased senescence marker staining in several neuroanatomical structures, including cortex, auditory cortex, dorsal lateral thalamic nucleus, geniculate nucleus, superior colliculus, ventral thalamic nucleus and hippocampus. In general, the increases in SA-β-gal activity were more pronounced at 1 month than at 24 h or 1 year post-blast and were also greater after repeated than single blast exposures. Real-time quantitative RT-PCR analysis revealed decreased levels of mRNA for senescence marker protein-30 (SMP-30) and increased mRNA levels for p21 (cyclin dependent kinase inhibitor 1A, CDKN1A), two other related protein markers of cellular senescence. The increased senescence observed in some of these affected brain structures may be implicated in several long-term sequelae after exposure to blast, including memory disruptions and impairments in movement, auditory and ocular functions.

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“…Degeneration and senescence of neurons are closely related to the performance of learning and memory (19). We found that the expression of β-Gal was increased in the hippocampus of APP/PS1 mice, while it was decreased after CCS treatment (Figure 1L&M).…”

Section: Ccs Improved Learning and Memory Impairment And Enhanced Hipmentioning

confidence: 88%

Cordycepin Improved Neuronal Synaptic Plasticity Through CREB-Induced NGF Up-Regulation Driven By Microglial M2 Polarization: A Symphony Communication Between Microglia and Neurons in AD

Jiao¹,

Liu²,

Zhong³

et al. 2021

Preprint

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Background: The purpose of this study was to explore the molecular mechanism of the neuroprotective effect of Cordycepin (CCS) on improving the neuro-immune microenvironment of AD neurons by mediating microglial M2 polarization. Methods: We investigated microglial M2 polarization from M1, neuronal senescence, and synaptic plasticity by biological techniques such as animal behavior, cell biology, morphology, and bioinformatics. Results: CCS improved learning and memory impairment in 9-month-old APP/PS1 mice. CCS induced the microglial M2 polarization, up-regulated the expression and secretion level of NGF, and inhibited neuronal apoptosis, senescence, and synaptic damage caused by abnormal microglial activation in vivo and in vitro. CREB was activated by the M2 polarization and mediated the NGF expression and secretion after CCS treatment. CREB bound with the Sg3 promoter region of NGF (-1018~-1011), which increased NGF expression and secretion. CREB-induced NGF upregulation driven by microglial M2 polarization to improve the neuronal synaptic plasticity inhibits neuronal apoptosis and senescence. As a novel participant in the intercellular communication between MG and neurons, NGF contributed to the neuroprotective efficacy of CCS treatment. Conclusions: CCS improved the neuronal synaptic plasticity and senescence by promoting microglial M2 activation driven by CERB-induced NGF upregulation and conducted the symphony communication of MG-Neuron in AD.

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Silibinin Alleviates the Learning and Memory Defects in Overtrained Rats Accompanying Reduced Neuronal Apoptosis and Senescence

Cited by 32 publications

References 62 publications

Is exercise a senolytic medicine? A systematic review

Is exercise a senolytic medicine? A systematic review

Blast Exposure Leads to Accelerated Cellular Senescence in the Rat Brain

Cordycepin Improved Neuronal Synaptic Plasticity Through CREB-Induced NGF Up-Regulation Driven By Microglial M2 Polarization: A Symphony Communication Between Microglia and Neurons in AD

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