High salt diet induces cognitive impairment and is linked to the activation of IGF1R/mTOR/p70S6K signaling.

A high-salt diet (HSD) has been associated with various health issues, including hypertension and cardiovascular diseases. However, recent studies have revealed a potential link between high salt intake and cognitive impairment. This study aims to investigate the effects of high salt intake on autophagy, tau protein hyperphosphorylation, and synaptic function and their potential associations with cognitive impairment. To explore these mechanisms, 8-month-old male C57BL/6 mice were fed either a normal diet (0.4% NaCl) or an HSD (8% NaCl) for 3 months, and Neuro-2a cells were incubated with normal medium or NaCl medium (80 mM). Behavioral tests revealed learning and memory deficits in mice fed the HSD. We further discovered that the HSD decreased autophagy, as indicated by diminished levels of the autophagy-associated proteins Beclin-1 and LC3, along with an elevated p62 protein level. HSD feeding significantly decreased insulin-like growth factor-1 receptor (IGF1R) expression in the brain of C57BL/6 mice and activated mechanistic target of rapamycin (mTOR) signaling. In addition, the HSD reduced synaptophysin and postsynaptic density protein 95 (PSD95) expression in the hippocampus and caused synaptic loss in mice. We also found amyloid ß accumulation and hyperphosphorylation of tau protein at different loci both in vivo and in vitro. Overall, this study highlights the clinical significance of understanding the impact of an HSD on cognitive function. By targeting the IGF1R/mTOR/p70S6K pathway or promoting autophagy, it may be possible to mitigate the negative effects of high salt intake on cognitive function.

Isolated unilateral brachial plexus injury following carbon monoxide intoxication: a case report and literature review.

Carbon monoxide (CO) is a gas that has no odor or color, making it difficult to detect until exposure leads to coma or death. CO poisoning is one of the most common and deadly poisonings around the world. CO poisoning is a common and often fatal form of poisoning worldwide. A toxic effect of CO is tissue hypoxia, which leads to systemic complications. Additionally, there may be severe neurological symptoms and delayed complications following CO poisoning. However, peripheral neuropathy is relatively rare after CO poisoning. Previously, only one case of unilateral plexopathy after CO poisoning, accompanied by rhabdomyolysis and cognitive dysfunction, has been reported. In this report, an isolated unilateral brachial plexopathy following CO intoxication is described. A key mechanism in this case may be CO-induced spinal cord ischemia. Immediate administration of hyperbaric oxygen therapy (HBOT) is crucial to prevent peripheral neuropathy after acute CO intoxication. Hyperbaric oxygen therapy (HBOT) should be administered immediately after acute CO intoxication to prevent peripheral neuropathy. Additionally, peripheral neuropathy following acute CO intoxication may benefit from consistent rehabilitation training.

Dietary salt promotes cognition impairment through GLP-1R/mTOR/p70S6K signaling pathway.

Dietary salt has been associated with cognitive impairment in mice, possibly related to damaged synapses and tau hyperphosphorylation. However, the mechanism underlying how dietary salt causes cognitive dysfunction remains unclear. In our study, either a high-salt (8%) or normal diet (0.5%) was used to feed C57BL/6 mice for three months, and N2a cells were cultured in normal medium, NaCl medium (80 mM), or NaCl (80 mM) + Liraglutide (200 nM) medium for 48 h. Cognitive function in mice was assessed using the Morris water maze and shuttle box test, while anxiety was evaluated by the open field test (OPT). Western blotting (WB), immunofluorescence, and immunohistochemistry were utilized to assess the level of Glucagon-like Peptide-1 receptor (GLP-1R) and mTOR/p70S6K pathway. Electron microscope and western blotting were used to evaluate synapse function and tau phosphorylation. Our findings revealed that a high salt diet (HSD) reduced the level of synaptophysin (SYP) and postsynaptic density 95 (PSD95), resulting in significant synaptic damage. Additionally, hyperphosphorylation of tau at different sites was detected. The C57BL/6 mice showed significant impairment in learning and memory function compared to the control group, but HSD did not cause anxiety in the mice. In addition, the level of GLP-1R and autophagy flux decreased in the HSD group, while the level of mTOR/p70S6K was upregulated. Furthermore, liraglutide reversed the autophagy inhibition of N2a treated with NaCl. In summary, our study demonstrates that dietary salt inhibits the GLP-1R/mTOR/p70S6K pathway to inhibit autophagy and induces synaptic dysfunction and tau hyperphosphorylation, eventually impairing cognitive dysfunction.

Enriched oxygen improves age-related cognitive impairment through enhancing autophagy.

Age-related cognitive impairment represents a significant health concern, with the understanding of its underlying mechanisms and potential interventions being of paramount importance. This study aimed to investigate the effects of hyperbaric oxygen therapy (HBOT) on cognitive function and neuronal integrity in aged (22-month-old) C57BL/6 mice. Male mice were exposed to HBOT for 2 weeks, and spatial learning and memory abilities were assessed using the Morris water maze. We employed transcriptome sequencing and Gene Ontology (GO) term enrichment analysis to examine the effects of HBOT on gene expression profiles, with particular attention given to synapse-related genes. Our data indicated a significant upregulation of postsynapse organization, synapse organization, and axonogenesis GO terms, likely contributing to improved cognitive performance. Moreover, the hyperphosphorylation of tau, a hallmark of many neurodegenerative diseases, was significantly reduced in the HBO-treated group, both in vivo and in vitro. Transmission electron microscopy revealed significant ultrastructural alterations in the hippocampus of the HBOT group, including an increase in the number of synapses and the size of the active zone, a reduction in demyelinated lesions, and a decreased number of "PANTHOS." Furthermore, Western blot analyses confirmed the upregulation of PSD95, BDNF, and Syn proteins, suggesting enhanced synaptic plasticity and neurotrophic support. Moreover, HBOT increased autophagy, as evidenced by the elevated levels of Beclin-1 and LC3 proteins and the reduced level of p62 protein. Finally, we demonstrated that HBOT activated the AMPK-mTOR signaling pathway, a critical regulator of autophagy. Notably, our findings provide novel insights into the mechanisms by which HBOT ameliorates age-related cognitive impairment, suggesting the potential therapeutic value of this approach.

Microglia in brain aging: An overview of recent basic science and clinical research developments.

Aging is characterized by progressive degeneration of tissues and organs, and it is positively associated with an increased mortality rate. The brain, as one of the most significantly affected organs, experiences age-related changes, including abnormal neuronal activity, dysfunctional calcium homeostasis, dysregulated mitochondrial function, and increased levels of reactive oxygen species. These changes collectively contribute to cognitive deterioration. Aging is also a key risk factor for neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. For many years, neurodegenerative disease investigations have primarily focused on neurons, with less attention given to microglial cells. However, recently, microglial homeostasis has emerged as an important mediator in neurological disease pathogenesis. Here, we provide an overview of brain aging from the perspective of the microglia. In doing so, we present the current knowledge on the correlation between brain aging and the microglia, summarize recent progress of investigations about the microglia in normal aging, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, and then discuss the correlation between the senescent microglia and the brain, which will culminate with a presentation of the molecular complexity involved in the microglia in brain aging with suggestions for healthy aging.

High-fat diet induces cognitive impairment through repression of SIRT1/AMPK-mediated autophagy.

AIMS: Recent evidence suggests an association between a high-fat diet (HFD) and cognitive decline. HFD may reduce synaptic plasticity and cause tau hyperphosphorylation, but the mechanisms involved remain unclear. The purpose of this study was to explore whether Sirtuin1 (SIRT1)/AMP-activated protein kinase (AMPK) pathway was involved in this pathogenic effect in the HFD exposed mice. METHODS: C57BL/6 mice at 12 months of age were fed a standard (9% kcal fat) or high-fat (60% kcal fat) diet for 22 weeks, and Neuro-2a (N2a) cells were treated with normal culture medium or a palmitic acid (PA) medium (100uM) for 40 h. After that, cognitive function was tested by Morris water maze (MWM). The levels of proteins involved in SIRT1/AMPK pathway and autophagy were measured using western blotting and immunofluorescence. We also assessed the phosphorylation of tau protein and synapse. RESULTS: The mice presented impaired learning and memory abilities. We further found decreased levels of synaptophysin (Syn) and brain-derived neurotrophic factor (BDNF), increased tau46 and phosphorylated tau protein, and damaged neurons in mice after HFD or in N2a cells treated with PA medium. Moreover, HFD can also reduce the expression of SIRT1, inhibit AMPK phosphorylation, and block autophagic flow in both mice and cells. After treating the cells with the SIRT1 agonist SRT1720, SIRT1/AMPK pathway and autophagy-related proteins were partially reversed and the number of PA-induced positive cells was alleviated in senescence-associated ß-galactosidase (SA-ß-gal) staining. CONCLUSIONS: HFD may inhibit the expression of SIRT1/AMPK pathway and disrupt autophagy flux, and result in tau hyperphosphorylation and synaptic dysfunction during aging, which ultimately lead to cognitive decline.

No relationship between right-to-left shunt with the severity of white matter hyperintensities.

INTRODUCTION: Studies have shown that right-to-left shunt (RLS) is closely related to the occurrence of white matter hyperintensities (WMHs). Therefore, the detection of RLS is of great significance for the diagnosis and treatment of cerebral small vessel disease, especially for the prevention and treatment of WMHs. In this study, the c-TCD foaming experiment was selected to screen RLS, and evaluate the correlation between RLS and the severity of WMHs. METHODS: We enrolled 334 migraineurs from a multicentre study from July 1 2019 and January 31 2020. Participants were all evaluated using contrast-enhanced transcranial Doppler, magnetic resonance imaging (MRI), and completed a questionnaire covering demographics, the main risk factors of vascular disease, and migraine status. RLS was classified into four grades (Grade 0 = Negative; Grade I = 1 ≤microbubbles (MBs)≤ 10; Grade II = MBs > 10 and no curtain; Grade III = curtain). Silent brain ischemic infarctions (SBI) and white matter hyperintensities (WMHs) were evaluated on MRI. RESULTS: In the incidence of WMHs, we found a significant difference between patients with RLS and no RLS (p < 0.05). There is no relationship between different grades of RLS and the severity of WMHs (p > 0.05). CONCLUSION: Overall, the positive rate of RLS is related to the incidence of WMHs. The different grades of RLS have no-relationship to do with the severity of WMHs.

Dysfunction of the neurovascular unit in brain aging.

An emerging concept termed the neurovascular unit (NVU) underlines neurovascular coupling. It has been reported that NVU impairment can result in neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Aging is a complex and irreversible process caused by programmed and damage-related factors. Loss of biological functions and increased susceptibility to additional neurodegenerative diseases are major characteristics of aging. In this review, we describe the basics of the NVU and discuss the effect of aging on NVU basics. Furthermore, we summarize the mechanisms that increase NVU susceptibility to neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Finally, we discuss new treatments for neurodegenerative diseases and methods of maintaining an intact NVU that may delay or diminish aging.

Promotion of astrocyte-neuron glutamate-glutamine shuttle by SCFA contributes to the alleviation of Alzheimer's disease.

The brain is particularly susceptible to oxidative damage which is a key feature of several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease. The shuttling of glutathione (GSH) precursors from astrocytes to neurons has been shown to be instrumental for the neuroprotective activity. Here, we revealed that short chain fatty acids (SCFA), which have been related to AD and PD, could promote glutamate-glutamine shuttle to potentially resist oxidative damage in neurons at cellular level. Furthermore, we performed nine-month-long dietary SCFA supplementations in APPswe/PS1dE9 (APP/PS1) mice, and showed that it reshaped the homeostasis of microbiota and alleviated the cognitive impairment by reducing Aß deposition and tau hyperphosphorylation. Single-cell RNA sequencing analysis of the hippocampus revealed SCFA can enhance astrocyte-neuron communication including glutamate-glutamine shuttle, mainly by acting on astrocyte in vivo. Collectively, our findings indicate that long-term dietary SCFA supplementations at early aging stage can regulate the neuroenergetics to alleviate AD, providing a promising direction for the development of new AD drug.

Berberine Rescues D-Ribose-Induced Alzheimer's Pathology via Promoting Mitophagy.

Mitochondrial dysfunction is considered an early event of Alzheimer disease (AD). D-ribose is a natural monosaccharide that exists in cells, especially in mitochondria, and can lead to cognitive dysfunction. However, the reason for this is unclear. Berberine (BBR) is an isoquinoline alkaloid that can target mitochondria and has great prospect in the treatment of AD. The methylation of PINK1 reinforces the burden of Alzheimer's pathology. This study explores the role of BBR and D-ribose in the mitophagy and cognitive function of AD related to DNA methylation. APP/PS1 mice and N2a cells were treated with D-ribose, BBR, and mitophagy inhibitor Mdivi-1 to observe their effects on mitochondrial morphology, mitophagy, neuron histology, AD pathology, animal behavior, and PINK1 methylation. The results showed that D-ribose induced mitochondrial dysfunction, mitophagy damage, and cognitive impairment. However, BBR inhibition of PINK1 promoter methylation can reverse the above effects caused by D-ribose, improve mitochondrial function, and restore mitophagy through the PINK1-Parkin pathway, thus reducing cognitive deficits and the burden of AD pathology. This experiment puts a new light on the mechanism of action of D-ribose in cognitive impairment and reveals new insights in the use of BBR for AD treatment.

Dietary High-Fat Promotes Cognitive Impairment by Suppressing Mitophagy.

Dietary habits contribute to the characteristics of Alzheimer's disease (AD) and cognitive impairment, which are partly induced by the accumulation of hyperphosphorylated Tau, a microtubule-associated protein. In mice, a fat-rich diet facilitates cognitive dysfunction. However, the mechanism by which dietary fat damages the brain remains unclear. In this study, 13-month-old C57BL/6 mice were fed a normal or high-fat diet (HFD) for 6 months. Neuro-2a cells were incubated with the normal medium or palmitic acid (200 µM). Spatial memory was assessed utilizing a behavioral test. Further, western blotting and immunofluorescence techniques were used to determine the levels of mitophagy-related proteins. The synaptic morphology and phosphorylation of Tau proteins were also evaluated. Administration of HFD decreased the expression of synaptophysin and brain-derived neurotrophic factor expression, leading to significant damage to neurons. Tau protein hyperphosphorylation was detected at different loci both in vivo and in vitro. Significantly impaired learning and memory abilities, accompanied by impaired mitophagy-related processes, were observed in mice fed with HFD as compared to mice fed with normal food. In conclusion, high fatty-acid intake hinders mitophagy and upregulates Tau protein phosphorylation, including age-related synaptic dysfunction, which leads to cognitive decline.

Role of AMPK in autophagy.

Adenosine monophosphate-activated protein kinase (AMPK) is a significant energy sensor in the maintenance of cellular energy homeostasis. Autophagy is a highly conserved catabolic process that involves an intracellular degradation system in which cytoplasmic components, such as protein aggregates, organelles, and other macromolecules, are directed to the lysosome through the self-degradative process to maintain cellular homeostasis. Given the triggered autophagy process in various situations including the nutrient deficit, AMPK is potentially linked with different stages of autophagy. Above all, AMPK increases ULK1 activity by directly phosphorylating Ser467, Ser555, Thr574, and Ser637 at least four sites, which increases the recruitment of autophagy-relevant proteins (ATG proteins) to the membrane domains which affects autophagy at the initiation stage. Secondly, AMPK inhibits VPS34 complexes that do not contain pro-autophagic factors and are thus involved in isolation membrane forming processes, by direct phosphorylation of VPS34 on Thr163 and Ser165. After phosphorylation, AMPK can govern autophagosome formation through recruiting downstream autophagy-related proteins to the autophagosome formation site. Finally, the AMPK-SIRT1 signaling pathway can be activated by upregulating the transcription of autophagy-related genes, thereby enhancing autophagosome-lysosome fusion. This review provides an introduction to the role of AMPK in different stages of autophagy.

Role of angiotensin II in aging.

Aging is an inevitable progressive decline in physiological organ function that increases the chance of disease and death. The renin-angiotensin system (RAS) is involved in the regulation of vasoconstriction, fluid homeostasis, cell growth, fibrosis, inflammation, and oxidative stress. In recent years, unprecedented advancement has been made in the RAS study, particularly with the observation that angiotensin II (Ang II), the central product of the RAS, plays a significant role in aging and chronic disease burden with aging. Binding to its receptors (Ang II type 1 receptor - AT1R in particular), Ang II acts as a mediator in the aging process by increasing free radical production and, consequently, mitochondrial dysfunction and telomere attrition. In this review, we examine the physiological function of the RAS and reactive oxygen species (ROS) sources in detail, highlighting how Ang II amplifies or drives mitochondrial dysfunction and telomere attrition underlying each hallmark of aging and contributes to the development of aging and age-linked diseases. Accordingly, the Ang II/AT1R pathway opens a new preventive and therapeutic direction for delaying aging and reducing the incidence of age-related diseases in the future.

Contribution of intracranial artery stenosis to white matter hyperintensities progression in elderly Chinese patients: A 3-year retrospective longitudinal study.

Background and purpose: There have been controversial results in previous studies for the association between intracranial artery stenosis (ICAS) and white matter hyperintensities (WMHs), and the correlation of ICAS with the progression of WMHs is uncertain. The aim of this study was to investigate the association between ICAS and the progression of WMHs. Methods: In this retrospective longitudinal study, we enrolled 302 patients aged 60 years and older who had received two brain MRI scans with a 3-year interval and was examined by CTA in the first MRI scan. We measured the stenosis of major intracranial arteries by CTA and assessed the progression of WMHs using the modified Rotterdam Progression scale (mRPS). We performed binary logistic regression analyses and established linear regression model to determine the relationship between the degree of ICAS and the progression of WMHs. Results: A total of 302 patients were enrolled, of which 48.3% experienced WMHs progression. After adjustment for confounding factors, the patients with Grade 2 ICAS had an OR of 2.8 (95% CI 1.4-5.5), and those with Grade 3 ICAS had an OR of 3.0 (95% CI 1.2-7.3) for the progression of WMHs. The ICAS degree remained associated with PVWMHs but had an attenuated relation to SCWMHs. ICAS severity was significantly associated with WMHs progression scores, higher for Grade 3 ICAS [ß (SE) = 0.18 (0.18)] followed by Grade 2 ICAS [ß (SE) = 0.10 (0.15)] compared with Grade 1 ICAS. Conclusions: Patients with more severe ICAS are more likely to have WMHs progression and have distinct relevancy to PVWMHs and SCWMHs, which may provide clues for understanding mechanisms of WMHs progression.

Dietary Salt Disrupts Tricarboxylic Acid Cycle and Induces Tau Hyperphosphorylation and Synapse Dysfunction during Aging.

Dietary salt causes synaptic deficits and tau hyperphosphorylation, which are detrimental to cognitive function. However, the specific effects of a high-salt diet on synapse and tau protein remain poorly understood. In this study, aged (15-month-old) C57BL/6 mice received a normal (0.5% NaCl) or high-salt (8% NaCl) diet for 3 months, and N2a cells were treated with normal culture medium or a NaCl medium (40 mM). Spatial learning and memory abilities were tested using the Morris water maze. The levels of metabolites and related enzymes in the tricarboxylic acid (TCA) cycle were confirmed using liquid chromatography-tandem mass spectrometry, western blotting, and immunofluorescence. We also investigated synapse morphology and the phosphorylation of tau protein. Under the high-salt diet, mice displayed impaired learning and memory compared to mice fed the normal diet. Furthermore, excessive salt intake disturbed the TCA cycle in both animals and cells compared to the respective normal controls. High dietary salt reduced postsynaptic density protein 95 (PSD95) and brain-derived neurotrophic factor (BDNF) expression, impaired neurons, and caused synaptic loss in the mice. We also detected tau hyperphosphorylation at different sites (Thr205, Thr231, and Thr181) without increasing total tau levels in response to high salt treatment, both in vivo and in vitro. We concluded that elevated salt intake impairs the TCA cycle and induces tau hyperphosphorylation and synapse dysfunction during aging, which ultimately results in cognitive impairment.

A long-term high-fat diet influences brain damage and is linked to the activation of HIF-1α/AMPK/mTOR/p70S6K signalling.

High-fat diets (HFDs) are related to the incidence of obesity and diabetes, but the effect of high-fat diet-induced brain damage remains to be clarified. In our study, we found that 24 weeks of a HFD effectively induced obesity and a change in fur color in mice. In addition, the mice also exhibited deficits in learning and memory. We further found that autophagic flux was impaired in mice after HFD feeding. Hypoxia-inducible factor 1α (HIF-1α) expression was significantly increased in HFD-fed mice, and HFD feeding inhibited adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and induced mechanistic target of rapamycin (mTOR) phosphorylation and p70S6K expression. Treatment of HFD-induced BV2 cell model with palmitic acid (PA) was used to further verify a similar result. We concluded that improving tissue hypoxia or enhancing autophagy through the AMPK/mTOR/p70S6K pathway may be a relevant strategy for improving obesity- and ageing-related disorders.

SIRT3 regulates mitochondrial biogenesis in aging-related diseases.

Sirtuin 3 (SIRT3), the main family member of mitochondrial deacetylase, targets the majority of substrates controlling mitochondrial biogenesis via lysine deacetylation and modulates important cellular functions such as energy metabolism, reactive oxygen species production and clearance, oxidative stress, and aging. Deletion of SIRT3 has a deleterious effect on mitochondrial biogenesis, thus leading to the defect in mitochondrial function and insufficient ATP production. Imbalance of mitochondrial dynamics leads to excessive mitochondrial biogenesis, dampening mitochondrial function. Mitochondrial dysfunction plays an important role in several diseases related to aging, such as cardiovascular disease, cancer and neurodegenerative diseases. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) launches mitochondrial biogenesis through activating nuclear respiratory factors. These factors act on genes, transcribing and translating mitochondrial DNA to generate new mitochondria. PGC1α builds a bridge between SIRT3 and mitochondrial biogenesis. This review described the involvement of SIRT3 and mitochondrial dynamics, particularly mitochondrial biogenesis in aging-related diseases, and further illustrated the role of the signaling events between SIRT3 and mitochondrial biogenesis in the pathological process of aging-related diseases.

Status epilepticus with focal neurologic deficits: a rare presentation of Neurosyphilis.

Neurosyphilis is a late complication of primary syphilis and occurs with a multitude of vague symptoms. In this study, we report a patient with neurosyphilis who presented with status epilepticus, hemiplegia, and aphasia, which may be easily misdiagnosed. After performing the reactive serum test, including the toluidine red unheated serum test and the Treponema pallidum particle agglutination assay test, and cerebrospinal fluid analysis, as well as the brain Magnetic Resonance Imaging (MRI) results, we consider it general paresis of the insane, also known as dementia paralytica. The patient was started on a 14-day course with high-dose intravenous penicillin. After this treatment, the patient made significant recovery with improved cognitive function, evidenced by his Mini-mental State Examination score of 21. However, before this treatment, he could not cooperate with this exam. General paresis of the insane typically has a progressive course and normally presents 10 to 30 years after the initial infection. The manifestations of this patient and his suspicious history of transient ischemic attacks may mislead to the diagnosis of Todd's paresis or stroke. The prevalence of syphilis has been rising again in recent years. To date, there is no gold standard for the diagnosis of neurosyphilis. Early diagnosis is of great importance, as penicillin therapy is highly effective.

Ameliorating Alzheimer's-like Pathology by Minocycline via Inhibiting Cdk5/p25 Signaling.

BACKGROUND: Minocycline has multiple neuroprotective roles in abundant brain diseases, including the prevention and treatment of Alzheimer's disease (AD). Cdk5/p25 signaling plays an important role in the onset and development of Alzheimer's-like pathology. The aim of the present work was to further explore the underlying mechanism which minocycline effects on Cdk5/p25 signaling related to Alzheimer's-like pathology. METHODS: The cognitive function of animals was measured by the Morris water maze test. The levels of Aß were determined by an enzyme-linked immunosorbent assay. The levels of APP, ß- and γ- secretases, and the biomarkers of tau (total tau and hyperphosphorylated tau), inflammatory cytokine and matrix metalloproteinases (MMP-2 and MMP-9), and biomarkers of synapse and Cdk5/p25 signaling, were detected by the Western blotting. The biomarkers of the synapse, inflammatory cytokine, and matrix metalloproteinases (MMP-2 and MMP-9) were also determined by immunofluorescence. RESULTS: Minocycline improved learning and memory in APP/PS1 mice. It limited the production of Aß and hyperphosphorylation of tau in the hippocampus and ameliorated synaptic deficit. Moreover, it also inhibited the activation of Cdk5/p25 signaling, inflammation, and matrix metalloproteinases. CONCLUSION: Minocycline mitigates Alzheimer's-like pathology via limiting the activation of Cdk5/p25 signaling pathway and improves cognitive deficits.

Role of mitophagy in the hallmarks of aging.

Aging, subjected to scientific scrutiny, is extensively defined as a time-dependent decline in functions that involves the majority of organisms. The time-dependent accretion of cellular lesions is generally a universal trigger of aging, while mitochondrial dysfunction is a sign of aging. Dysfunctional mitochondria are identified and removed by mitophagy, a selective form of macroautophagy. Increased mitochondrial damage resulting from reduced biogenesis and clearance may promote the aging process. The primary purpose of this paper is to illustrate in detail the effects of mitophagy on aging and emphasize the associations between mitophagy and other signs of aging, including dietary restriction, telomere shortening, epigenetic alterations, and protein imbalance. The evidence regarding the effects of these elements on aging is still limited. And although the understanding of relationship between mitophagy and aging has been long-awaited, to analyze details of such a relationship remains the main challenge in aging studies.