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QJD alleviated the pathological alterations in the hippocampus of D-gal–induced mice. (A) Representative HE staining images in the hippocampus of CA1 and CA3 regions (magnification × 400; scale bar = 20 μm). (B) Representative FJB staining images (labeled in green) in the hippocampus of CA1 and CA3 regions (magnification × 400; scale bar: 20 μm). (C) Number of FJB-positive neurons in the hippocampus CA1 region. (D) Number of FJB-positive neurons in the hippocampus CA3 region. The blue arrows indicate damaged neurons in the hippocampus. All data were presented as mean ± SEM (n = 4/group). **p < 0.01 vs. NC group; # p < 0.05 and ## p < 0.01 vs. D-gal group.
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Qiangji Decoction (QJD), a classic formula, has been widely used to treat brain aging–related neurodegenerative diseases. However, the mechanisms underlying QJD’s improvement in cognitive impairment of neurodegenerative diseases remain unclear. In this study, we employed D-galactose to establish the model of brain aging by long-term D-galactose sub...
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... A sufficient number of neurons with synaptic connections are necessary for cognitive, learning, and memory functions [46]. In a previous study, D-gal exposure of rats resulted in disordered cell alignment, nuclear contraction, or apoptosis in the hippocampus [47]. Our data also showed that the normal cell number in the CA1 and DG regions of Nissl staining in hippocampal tissue of D-gal-exposed rats was reduced significantly, and the solid shrinkage cell number and disordered cell arrangement were increased. ...
Recent studies have indicated that fucoidan has the potential to improve cognitive impairment. The objective of this study was to demonstrate the protective effect and possible mechanisms of fucoidan in D-galactose (D-gal)-induced cognitive dysfunction. Sprague Dawley rats were injected with D-galactose (200 mg/kg, sc) and administrated with fucoidan (100 mg/kg or 200 mg/kg, ig) for 8 weeks. Our results suggested that fucoidan significantly ameliorated cognitive impairment in D-gal-exposed rats and reversed histopathological changes in the hippocampus. Fucoidan reduced D-gal-induced oxidative stress, declined the inflammation level and improved mitochondrial dysfunction in hippocampal. Fucoidan promoted mitochondrial biogenesis by regulating the PGC-1α/NRF1/TFAM pathway, thereby improving D-gal-induced mitochondrial dysfunction. The regulation effect of fucoidan on PGC-1α is linked to the upstream protein of APN/AMPK/SIRT1. Additionally, the neuroprotective action of fucoidan could be related to maintaining intestinal flora homeostasis with up-regulation of Bacteroidota, Muribaculaceae and Akkermansia and down-regulation of Firmicutes. In summary, fucoidan may be a natural, promising candidate active ingredient for age-related cognitive impairment interventions.
... D-gal induced aging was tied to hippocampal apoptosis, according to accumulating evidence [53,54]. We used Western blot to examine whether, GNL sup-plementation inhibited apoptosis. ...
D-galactose (D-gal) administration was proven to induce cognitive impairment and aging in rodents' models. Geraniol (GNL) belongs to the acyclic isoprenoid monoterpenes. GNL reduces inflammation by changing important signaling pathways and cytokines, and thus it is plausible to be used as a medicine for treating disorders linked to inflammation. Herein, we examined the therapeutic effects of GNL on D-gal-induced oxidative stress and neuroinflammation-mediated memory loss in mice. The study was conducted using six groups of mice (6 mice per group). The first group received normal saline, then D-gal (150 mg/wt) dissolved in normal saline solution (0.9%, w/v) was given orally for 9 weeks to the second group. In the III group, from the second week until the 10th week, mice were treated orally (without anesthesia) with D-gal (150 mg/kg body wt) and GNL weekly twice (40 mg/kg body wt) four hours later. Mice in Group IV were treated with GNL from the second week up until the end of the experiment. For comparison of young versus elderly mice, 4 month old (Group V) and 16-month-old (Group VI) control mice were used. We evaluated the changes in antioxidant levels, PI3K/Akt levels, and Nrf2 levels. We also examined how D-gal and GNL treated pathological aging changes. Administration of GNL induced a significant increase in spatial learning and memory with spontaneously altered behavior. Enhancing anti-oxidant and anti-inflammatory effects and activating PI3K/Akt were the mechanisms that mediated this effect. Further, GNL treatment upregulated Nrf2 and HO-1 to reduce oxidative stress and apoptosis. This was confirmed using 99mTc-HMPAO brain flow gamma bioassays. Thus, our data suggested GNL as a promising agent for treating neuroinflammation-induced cognitive impairment.
... apoptosis of hippocampal neurons can impair synaptic plasticity and regenerative function leading to progressive cognitive decline. 4 In an era of global population aging, it is imperative to understand the molecular basis underlying aging-related neuronal deficits and neurodegenerative disorders. ...
Brain aging is the most important risk factor for neurodegenerative disorders, and abnormal apoptosis is linked to neuronal dysfunction. Specifically, studies have found that exercise effectively inhibits hippocampal neuronal apoptosis, while the molecular mechanism remains unclear. In the present study, we investigated the impact of aerobic exercise on hippocampal neuronal apoptosis in aging mice and the potential involvement of DAPK1 and its downstream pathways based on recent data that DAPK1 may be associated with neuronal death in neurodegenerative diseases. Senescent mice were subjected to 8 weeks of Aerobic training. Following behavioral testing, hippocampal samples were examined histologically and biochemically to detect pathological changes, neuronal apoptosis, and mRNA and protein levels. We found that the exercise intervention improved spatial memory and alleviated neuronal apoptosis in the brain. Notably, exercise down‐regulated DAPK1 expression and inhibited Fas death receptor transactivation and the mitochondrial apoptotic pathway in the hippocampus. These results shed new light on the protective effect of regular exercise against brain aging though modulating the DAPK1 pathway.
... D-gal induced aging was tied to hippocampal apoptosis, according to accumulating evidence 34,35 . Here, we performed western blot to check the ability of GNL supplementation to inhibit apoptosis. ...
D-galactose (D-gal) is a reducing sugar drug can induce artificial senescence and aging process that mimic natural aging along with the accompanying brain and liver injury in experimental animals. Therefore, chronic D-gal administration is widely used to induce cognitive impairment, Alzheimer disease and aging in rodents' models. Aging is a phenomenon in which oxidative stress and apoptosis play a vital role. Geraniol (GNL) belongs to the acyclic isoprenoid monoterpenes, presents in essential oils such as those from Cinnamomum tenuipilum and Valeriana officinalis. In the present study, we examined the effects of GNL on D-gal-induced oxidative stress and neuro-inflammation mediated memory loss in mice. Analyzing the behavioral differences between control and treated groups, including the elderly mice, revealed that GNL significantly improved memory in mice treated with D-gal-induced memory loss (supplementary videos are provided). The anti-inflammatory and the anti-oxidative role of GNL were confirmed by both histopathological investigations and biochemical analyses. Mechanistically, GNL appears to activate PI3K/Akt and thus upregulates the nuclear factor erythroid 2-related factor 2 (Nrf2) and the heme oxygenase 1 (HO-1) to reduce the oxidative stress and apoptosis induced after D-gal treatment leading to easing of neurological deficits and cognitive dysfunction in D-gal-induced aging mouse models. Accordingly, our comprehensive behavioral analysis and bioassays suggest GNL as a promising agent preventing cognitive impairment and neurological deficits associated with aging.
Background and Purpose D-galactose (D-gal) administration was proven. to induce cognitive impairment, Alzheimer disease and aging in rodents’ models. Geraniol (GNL) belongs to the acyclic isoprenoid monoterpenes. Herein, we examined the therapeutic effects of GNL on D-gal-induced oxidative stress and neuro-inflammation mediated memory loss in mice. Experimental Approach The study was conducted using six group of mice (6 mice per group). The Ist group received normal saline, then D-gal (150 mg/wt) dissolved in normal saline solution (0.9%, w/v) was given orally for 9 weeks to the second group. From the second week until the 10th week, mice were treated orally (without anesthesia) with D-gal (150 mg/wt) followed by GNL (40 mg/kg/wt) four hours later. Mice of group IV were treated with GNL from the second week up until the end of the experiment. The therapeutic effects of GNL on D-gal-induced oxidative stress and neuro-inflammation mediated memory loss in mice was evaluated. For comparison of young versus elderly mice, (Group V) and 16 (what are 4 and 6) (group VI) month old control mice were used. Key Results Administration of GNL induced a significant increase in spatial learning and memory with spontaneously altered behavior. This effects was mediated through improving anti-oxidant and anti-inflammatory levels and activating PI3K/Akt. Further, GNL treatment upregulated the NRF-2 and HO-1 to reduce the oxidative stress and apoptosis. That was confirmed using 99mTc-HMPAO brain flow gamma bioassays. Conclusion and Implications Geraniol could be used as a promising agent in treating neuro-inflammation induced cognitive impairment.
Obsessive-Compulsive disorder (OCD) is a long-term and persistent mental illness characterised by obsessive thoughts and compulsive behaviours. Numerous factors can contribute to the development or progression of OCD. These factors may result from the dysregulation of multiple intrinsic cellular pathways, including SIRT-1, Nrf2, and HO-1. Inhibitors of selective serotonin reuptake (SSRIs) are effective first-line treatments for OCD. In our ongoing research, we have investigated the role of SIRT-1, Nrf2, and HO-1, as well as the neuroprotective potential of Acetyl-11-keto-beta boswellic acid (AKBA) against behavioural and neurochemical changes in rodents treated with 8-OH-DPAT. In addition, the effects of AKBA were compared to those of fluvoxamine (FLX), a standard OCD medication. Injections of 8-OH-DPAT into the intra-dorso raphe nuclei (IDRN) of rats for seven days induced repetitive and compulsive behaviour accompanied by elevated oxidative stress, inflammatory processes, apoptosis, and neurotransmitter imbalances in CSF, blood plasma, and brain samples. Chronic administration of AKBA at 50mg/kg and 100mg/kg p.o. restored histopathological alterations in the cortico-striatal-thalamo-cortical (CSTC) pathway, including the cerebral cortex, striatum, and hippocampal regions. Our investigation revealed that when AKBA and fluvoxamine were administered together, the alterations were restored to a greater degree than when administered separately. These findings demonstrate that the neuroprotective effect of AKBA can serve as an effective basis for developing a novel OCD treatment. DATA AVAILABILITY STATEMENT: All data generated or analyzed during this study are included in this article. There are no separate or additional files.
Subcortical ischemic vascular dementia (SIVD), which is caused by chronic cerebral hypoperfusion, is a common subtype of vascular dementia, accompanied by white matter damage and cognitive impairment. Currently, there are no effective treatments for this condition. Oxidative stress is a key factor in the pathogenesis of white matter damage. Astragaloside IV (AS-IV), one of the main active components of astragaloside, has antioxidant properties and promotes cognitive improvement; however, its effect on SIVD and its potential mechanism remain unknown. We aimed to clarify whether AS-IV had a protective effect against SIVD injury caused by right unilateral common carotid artery occlusion and the underlying mechanism. The results showed that AS-IV treatment improved cognitive function and white matter damage, inhibited oxidative stress and glial cells activation, and promoted the survival of mature oligodendrocytes after chronic cerebral hypoperfusion. Moreover, the protein expression levels of NQO1, HO-1, SIRT1 and Nrf2 were increased by AS-IV treatment. However, pre-treatment with EX-527, a SIRT1-specific inhibitor, eliminated the beneficial effects of AS-IV. These results demonstrate that AS-IV plays a neuroprotective role in SIVD by suppressing oxidative stress and increasing the number of mature oligodendrocytes via the modulation of SIRT1/Nrf2 signaling. Our results support AS-IV as a potential therapeutic agent for SIVD.
