Curcumin attenuates brain aging by reducing apoptosis and oxidative stress.

Brain aging is a physiological event, and oxidative stress and apoptosis are involved in the natural aging process of the brain. Curcumin is a natural antioxidant with potent anti-aging and neuroprotective properties. Therefore, we investigated the protective effects of curcumin on brain apoptosis and oxidative stress, brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF) in aged rats. Old female Wistar rats were randomly divided into three groups (n = 7); as follows: (1) control; (2); saline and (3) curcumin (received 30 mg/kg of curcumin, 5 days/week for 8 weeks, intraperitoneally). Our results indicated that treatment with curcumin in aged rats attenuates brain lipid peroxidation, which was accompanied by a significant increase in the BDNF, VEGF, superoxide dismutase (SOD) activity, and anti-apoptotic protein BCl-2. No significant change in brain anti-apoptotic Bax protein levels was observed after curcumin treatment. The study indicates that curcumin could alleviate brain aging which may be due to attenuating oxidative stress, inhibiting apoptosis, and up-regulating SOD activity, which in turn enhances VEGF and BDNF. Therefore, curcumin has potential therapeutic value in the treatment of neurological apoptosis, neurogenesis, and angiogenesis changes caused by brain aging.

Involvement of Fgf2-mediated tau protein phosphorylation in cognitive deficits induced by sevoflurane in aged rats.

OBJECTIVE: Anesthetics have been linked to cognitive alterations, particularly in the elderly. The current research delineates how Fibroblast Growth Factor 2 (Fgf2) modulates tau protein phosphorylation, contributing to cognitive impairments in aged rats upon sevoflurane administration. METHODS: Rats aged 3, 12, and 18 months were subjected to a 2.5% sevoflurane exposure to form a neurotoxicity model. Cognitive performance was gauged, and the GEO database was employed to identify differentially expressed genes (DEGs) in the 18-month-old cohort post sevoflurane exposure. Bioinformatics tools, inclusive of STRING and GeneCards, facilitated detailed analysis. Experimental validations, both in vivo and in vitro, examined Fgf2's effect on tau phosphorylation. RESULTS: Sevoflurane notably altered cognitive behavior in older rats. Out of 128 DEGs discerned, Fgf2 stood out as instrumental in regulating tau protein phosphorylation. Sevoflurane exposure spiked Fgf2 expression in cortical neurons, intensifying tau phosphorylation via the PI3K/AKT/Gsk3b trajectory. Diminishing Fgf2 expression correspondingly curtailed tau phosphorylation, neurofibrillary tangles, and enhanced cognitive capacities in aged rats. CONCLUSION: Sevoflurane elicits a surge in Fgf2 expression in aging rats, directing tau protein phosphorylation through the PI3K/AKT/Gsk3b route, instigating cognitive aberrations.

The effect of TEMPOL pretreatment on postoperative cognitive function, inflammatory response, and oxidative stress in aged rats under sevoflurane anesthesia.

INTRODUCTION: The heterocyclic compound 4-hydroxy-(2,2,6,6-Tetramethylpiperidin-1-yl)oxyl (TEMPOL) has a protective effect on neurological function in brain tissues damaged by ischemia and hypoxia. This study explored the effects of TEMPOL pretreatment on postoperative cognitive function in aged rats under sevoflurane anesthesia, focusing on inflammatory response and oxidative stress. METHODS: Sixty male rats were divided into normal control (C), sevoflurane anesthesia (S), TEMPOL pretreatment (T), and sevoflurane anesthesia + TEMPOL pretreatment (ST) groups (15 per group). Groups T and ST rats received continuous intraperitoneal TEMPOL (100 mg/kg) for 3 days, while groups C and S rats were injected with 0.9% saline. After pretreatment, groups S and ST received 3% sevoflurane anesthesia. RESULTS: Rats in group S exhibited a longer swimming distance, longer escape latency, lower frequency of platform crossing, and shorter dwell time in the targeted quadrant than those in groups C and T. Rats in group ST exhibited a shorter swimming distance, shorter escape latency, higher frequency of platform crossing, and longer dwell time in the targeted quadrant than those in group S. The expressions of interleukin-6, tumor necrosis factor-α, inducible nitric oxide synthase, and Ym1/2 messenger ribonucleic acid were higher in groups S and ST rats than in groups C and T rats and lower in group ST rats than in group S rat (p < .05). Superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px) were lower, while malondialdehyde (MDA) was higher in groups S and ST rats than in groups C and T rats (p < .05). Group ST showed higher SOD, T-AOC, and GSH-Px, and lower MDA than group S (p < .05). CONCLUSIONS: TEMPOL pretreatment attenuated postoperative cognitive impairment induced by sevoflurane anesthesia in aged rats. This may be attributed to the downregulation of NR2B-CREB-BDNF pathway, reducing the inflammatory response and oxidative stress damage in hippocampal tissue.

Reciprocal interaction between mitochondrial fission and mitophagy in postoperative delayed neurocognitive recovery in aged rats.

INTRODUCTION: Emerging evidence suggests that mitochondrial dysfunction plays a crucial role in the pathogenesis of postoperative delayed neurocognitive recovery (dNCR). Mitochondria exist in a dynamic equilibrium that involves fission and fusion to regulate morphology and maintains normal cell function via the removal of damaged mitochondria through mitophagy. Nonetheless, the relationship between mitochondrial morphology and mitophagy, and how they influence mitochondrial function in the development of postoperative dNCR, remains poorly understood. Here, we observed morphological alterations of mitochondria and mitophagy activity in hippocampal neurons and assessed the involvement of their interaction in dNCR following general anesthesia and surgical stress in aged rats. METHODS: Firstly, we evaluated the spatial learning and memory ability of the aged rats after anesthesia/surgery. Hippocampal mitochondrial function and mitochondrial morphology were detected. Afterwards, mitochondrial fission was inhibited by Mdivi-1 and siDrp1 in vivo and in vitro separately. We then detected mitophagy and mitochondrial function. Finally, we used rapamycin to activate mitophagy and observed mitochondrial morphology and mitochondrial function. RESULTS: Surgery impaired hippocampal-dependent spatial learning and memory ability and caused mitochondrial dysfunction. It also increased mitochondrial fission and inhibited mitophagy in hippocampal neurons. Mdivi-1 improved mitophagy and learning and memory ability of aged rats by inhibiting mitochondrial fission. Knocking down Drp1 by siDrp1 also improved mitophagy and mitochondrial function. Meanwhile, rapamycin inhibited excessive mitochondrial fission and improved mitochondrial function. CONCLUSION: Surgery simultaneously increases mitochondrial fission and inhibits mitophagy activity. Mechanistically, mitochondrial fission/fusion and mitophagy activity interact reciprocally with each other and are both involved in postoperative dNCR. These mitochondrial events after surgical stress may provide novel targets and modalities for therapeutic intervention in postoperative dNCR.

Rapamycin Affects the Hippocampal SNARE Complex to Alleviate Cognitive Dysfunction Induced by Surgery in Aged Rats.

Delayed neurocognitive recovery (dNCR) is a common complication that occurs post-surgery, especially in elderly individuals. The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex plays an essential role in various membrane fusion events, such as synaptic vesicle exocytosis and autophagosome-lysosome fusion. Although SNARE complex dysfunction has been observed in several neurodegenerative disorders, the causal link between SNARE-mediated membrane fusion and dNCR remains unclear. We previously demonstrated that surgical stimuli caused cognitive impairment in aged rats by inducing α-synuclein accumulation, inhibiting autophagy, and disrupting neurotransmitter release in hippocampal synaptosomes. Here, we evaluated the effects of propofol anesthesia plus surgery on learning and memory and investigated levels of SNARE proteins and chaperones in hippocampal synaptosomes. Aged rats that received propofol anesthesia and surgery exhibited learning and memory impairments in a Morris water maze test and decreased levels of synaptosome-associated protein 25, synaptobrevin/vesicle-associated membrane protein 2, and syntaxin 1. Levels of SNARE chaperones, including mammalian uncoordinated-18, complexins 1 and 2, cysteine string protein-α, and N-ethylmaleimide-sensitive factor, were all significantly decreased following anesthesia with surgical stress. However, the synaptic vesicle marker synaptophysin was unaffected. The autophagy-enhancer rapamycin attenuated structural and functional disturbances of the SNARE complex and ameliorated disrupted neurotransmitter release. Our results indicate that perturbations of SNARE proteins in hippocampal synaptosomes may underlie the occurrence of dNCR. Moreover, the protective effect of rapamycin may partially occur through recovery of SNARE structural and functional abnormalities. Our findings provide insight into the molecular mechanisms underlying dNCR.

Investigation of the Renal Protective Effect of Combined Dietary Polyphenols in Streptozotocin-Induced Diabetic Aged Rats.

Natural polyphenols are widely reported to have a large range of pharmacological properties, especially antioxidant activities and free radical scavenging capacities. In this study, we investigate the effects of naringin, chlorogenic acid, and quercetin mixtures (NCQ) on renal fibrosis in streptozotocin (STZ)-induced diabetic aged rats and its underlying mechanisms for ten consecutive weeks. The oxidative defense system in the kidneys of treated rats was found to be improved. Several biomarkers were investigated including the blood urea nitrogen, creatinine, and uric acid. Moreover, antioxidant parameters were evaluated and we found that superoxide dismutase, catalase, glutathione peroxidase, Na+-K+-ATPase activities, the nitric oxide production, the protein carbonyl, the advanced oxidation protein products, lipid peroxidation, and reduced glutathione levels were all significantly balanced and close to control values. In addition, NCQ restored renal injuries and fibrosis as assessed by histological method and molecular biology investigation of the matrix metalloproteinase, the transforming growth factor-beta TGF-ß, the tumor necrosis factor TNFα, and p53 expression. Our study proposes the NCQ combination as potential plant-derived bioactive compounds to prevent diabetic nephropathy.

Nigella Fixed Oil mitigates memory impairment in a rat aged model of cognitive decline, a pivotal role of BDNF and CREB signaling pathways in the hippocampus.

BACKGROUND: Nigella is a plant widely used as a natural remedy, recent studies are being focused on the evaluation of its central effects. In this sense, the aim of this research is to explore the effects of the fixed oil of Nigella on cognitive decline in rats. METHODS: Behavioral evaluation was performed via a battery of tests, then quantification of Brain Derived Neurotrophic Factor and Cyclic AMP Response Element-Binding protein, mRNA in the hippocampus using RT PCR. RESULTS: The results indicated that the fixed oil of black cumin had no effect on spatial memory, whereas the treatment with black cumin induced an overexpression of BDNF, while the variability of CREB levels was not significant. CONCLUSION: This is the unique study conducted to so far, and we may conclude that Nigella fixed oil seems to have a therapeutic effect on cognitive decline.

Mdivi-1 improves postoperative neurocognitive disorders in aged rats undergoing splenectomy by inhibiting dynamin-related protein-1.

Background: The regulatory role of mitochondria in the inflammatory response of the nervous system postoperatively remains unclear. This study explored the relationship between mitochondria and postoperative neurocognitive dysfunction (PNCD) by regulating mitochondrial function in aged rats undergoing splenectomy. Methods: A total of 120 aged rats were randomly divided into five groups (n=24) as follows: Control group (not subjected to any form of treatment), Sham group (subjected only to sham-splenectomized operation after anesthesia), Splenectomy group (only underwent splenectomy after anesthesia), Synonyms Mitochondrial division inhibitor 1 (Mdivi-1) group [treated with Mdivi-1, a dynamin-relatedprotein 1 (Drp1) inhibitor], and Dimethyl Sulfoxide (DMSO) group (treated with DMSO, a solvent). Inflammatory markers, namely interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF-α), were measured in the plasma and brains of the rats. Cognitive function was assessed using the Morris water maze test. Results: During the perioperative period, the physiological parameters did not differ among the five groups (P>0.05). The results of the Morris water maze experiments showed that the memory of the rats was significantly impaired after splenectomy, which was alleviated by Mdivi-1 administration (P=0.04). Postoperatively, the proinflammatory cytokine levels in the serum and hippocampus tissue were upregulated, while Mdivi-1 administration reduced this increase. The electron microscopy and hematoxylin-eosin (HE) staining results indicated that the structure of neurons and mitochondria was minimally impaired in the Mdivi-1 group. Conclusions: Aged rats that underwent splenectomy exhibited significant postoperative cognitive impairments. The selective inhibitor of Drp1, Mdivi-1, exerted protective effects against PNCD by ameliorating mitochondrial dysfunction and reducing the inflammatory response.

Glibenclamide Attenuates Neuroinflammation and Promotes Neurological Recovery After Intracerebral Hemorrhage in Aged Rats.

Intracerebral hemorrhage (ICH) is a common disease in the elderly population. Inflammation following ICH plays a detrimental role in secondary brain injury, which is associated with a poor prognosis of patients with ICH, and no efficient pharmacological preventions are available. Here, we investigated the effects of glibenclamide (GLC) on neuroinflammation in an autoblood-induced aged rat (18 months old) model of ICH. Rats were randomized into the sham, vehicle, and GLC groups. First, we investigated the expression level of sulfonylurea receptor 1 (Sur1) surrounding the hematoma after ICH. Then, neurological scores were calculated, and water maze tests, brain water content analysis, western blotting, and immunofluorescence assays were implemented to detect the neuroprotective effect of GLC. The expression of the Sur1-Trpm4 channel was significantly increased in the perihematomal tissue following ICH in aged rats. The GLC administration effectively reduced brain edema and improved neurofunction deficits following ICH. In addition, GLC increased the expression of brain-derived neurotrophic factors and decreased the expression of proinflammatory factors [tumor necrosis factor (TNF)-α,interleukin (IL)-1, and IL-6]. Moreover, GLC markedly reduced Ikappa-B (IκB) kinase (IKK) expression in microglia and nuclear factor (NF)-κB-P65 levels in perihematomal tissue. GLC ameliorated ICH-induced neuroinflammation and improved neurological outcomes in aged rats. In part, GLC may exert these effects by regulating the NF-κB signaling pathway through the Sur1-Trpm4 channel.

Neurotropic peptide HLDF-6-amide reduces age-related decline in sexual activity in old male rats.

Aging is associated with a decline in the erectile capacity and sexual motivation. Emerging new therapy for the treatment of these age-related pathologies in men is the use of the regulatory peptides. We validated the use of HLDF-6-amide (Thr-Gly-Glu-Hse-His-Arg-NH2) as a potential modulator of sexual performance in aged male rats. Behavioral tests, including the standard parameters of sexual behavior, were performed longitudinally at 20 and 26 months of age. The effects of HLDF-6-amide administered daily at 300 µg/kg for 3 week on the levels of sex hormones and the activity of antioxidant enzymes and indicators of inflammation were evaluated. HLDF-6-amide administration increased the copulative activity of the 20-month-old male rats. This effect of HLDF-6-amide was more pronounced in the 26-month-old rats. Although HLDF-6-amide did not have the effect on the levels of circulating testosterone and estradiol, it reduced the activity of leukocyte elastase and glutathione-S-peroxidase, suggesting that the peptide has anti-inflammatory and antioxidant properties. Therefore, this study shows that HLDF-6-amide has the positive impact on sexual activity in this rodent model, representing a new therapeutic approach for improving sexual performance in older men.

Hirsutanol A exhibits neuroprotective activities against sevoflurane-induced neurotoxicity in aged rats.

The neurotoxicity of the inhaled anesthetic, sevoflurane, has been documented in a number of studies. In this study, we conducted experiments to investigate whether Hirsutanol A (HA), a sesquiterpene compound from the fungus, Chondrostereum sp., can provide protection from sevoflurane-induced neurological toxicity in aged rats, and analyzed the underlying mechanisms. The cognitive dysfunction of rats following sevoflurane exposure was evaluated by behavioral tests. The neuronal cell survival was determined by Nissl staining. In addition, human neuroblastoma H4 cells were exposed to sevoflurane to establish an in vitro model. Apoptotic marker expression in hippocampal tissue was determined by western blotting. Cell apoptosis in vitro was also examined by TUNEL assay and flow cytometry. The expression and translocation of Nrf2 were examined by both western blot and immunofluorescence staining. Our results show that HA significantly attenuated sevoflurane-induced cognitive impairment in aged rats. In addition, HA treatment decreased sevoflurane-induced neuronal apoptosis in the hippocampus and alleviated Aß accumulation. Our results also show that the neuroprotective effect of HA is associated with the activation of Nrf2 signaling. Human neuroblastoma H4 cells were used as a model to examine the protective activity of HA against sevoflurane-induced neurotoxicity. In addition, our results show that the inhibition of Nrf2 by a specific inhibitor or targeting siRNA significantly compromises the attenuating effect of HA on sevoflurane-induced cell apoptosis and Aß accumulation. Our results suggest that HA may function as a neuroprotective agent against sevoflurane-induced neurotoxicity.

Pentoxifylline enhances antioxidative capability and promotes mitochondrial biogenesis for improving age-related behavioral deficits.

Pentoxifylline (PTX) is a non-specific phosphodiesterase inhibitor with pleiotropic effects that is routinely used to treat peripheral vascular disease. In this study, we tested whether PTX could also counteract the detrimental effects of aging in the brain. To accomplish that, we treated aged rats with PTX and measured resulting behavioral alterations as well as changes in dopaminergic neurochemical levels, oxidative balance markers, mitochondrial function, nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator activated receptor-gamma coactivator 1-alpha (PGC-1α) and downstream gene expression, and cyclic adenosine monophosphate (cAMP) content in the brain. The results demonstrated that PTX improved motor and cognitive deficits and restored levels of dopamine and its metabolites in the brains of aged rats. PTX also reduced malondialdehyde levels and increased the GSH/GSSG ratio, mitochondrial ATP, nuclear Nrf2, and cAMP levels, and upregulated PGC-1α, nuclear respiratory factor 1, and mitochondrial transcription factor A expression in the substantia nigra and hippocampus of aged rats. Thus, increased nuclear Nrf2 levels and upregulation of PGC-1α, which enhance antioxidative capability and promote mitochondrial biogenesis, may be responsible for PTX-induced amelioration of behavioral deficits in aged rats.

Quercetin mitigates monosodium glutamate-induced excitotoxicity of the spinal cord motoneurons in aged rats via p38 MAPK inhibition.

Various studies reported the possibility of deterioration of blood-brain barrier (BBB) integrity owing to the aging process. The current work was performed to investigate the ability of Monosodium glutamate (MSG) to cross BBB in aged rats, the damage affecting the anterior horn cells of the spinal cord due to excitotoxicity, and the mechanisms by which quercetin (Que) administration might suppress such damage. Forty male rats aged 18 months were assigned equally to 4 groups: control group, Que group (received Que, 20 mg/kg/d intraperitonealy for 10 days), MSG group (received MSG, 4.0 g/kg/d subcutaneously for 10 days), MSG + Que group (received both Que and MSG as done in the Que and MSG groups respectively). Cervical spinal cord specimens were obtained and prepared for routine histological study, immunohistochemical staining by caspase-3 and glial fibrillary acidic protein (GFAP), assessment of oxidative stress, measurement of cytokines, assessment of caspase-3 activity and GFAP levels as well as for western blotting of phosphorylated activating transcription factor 2 (ATF2pp) as an indicator for the activity of p38 mitogen-activated protein kinase (MAPK). The MSG group revealed variable degenerative and apoptotic changes in the motoneurons and neuroglia, a marked rise in the cytoplasmic caspase-3 expression in motoneurons and a significant reduction (p < 0.001) in the astrocyte surface area percentage. In addition, the spinal cord tissue exhibited a significant elevation (p < 0.001) in the levels of malondialdehyde (MDA), IL-1, IL-6, TNFα, INFÉ£, caspase-3 activity and ATF2 pp expression as well as a significant reduction (p < 0.001) in SOD, IL-10 and GFAP levels compared with the control group. On combining Que with MSG, most of the degenerative changes were reversed and all the impaired parameters were nearly normalized except for IL-6 and GFAP levels which were still significantly (p < 0.05) different from those of the control group. Our study suggests that MSG can break through the BBB of the aged rats and induce excitotoxicity dependent changes in spinal cord motoneurons. Most of these changes were reversed by Que probably via targeting the p38 MAPK-ATF2 pathway, antagonizing oxidative stress, anti-inflammatory effect, and promoting GFAP expression.

Cigarette smoke extract triggers neoplastic change in lungs and impairs locomotor activity through wnt3a-ß-catenin signaling in aged COPD rodent model.

BACKGROUND: Chronic cigarette smoking primes immense decline in lung functions and retardation of motor functions with increase in age. This raise the question of whether age status overwhelm the susceptibility to smoking induced lung inflammatory diseases and neuro-motor dysfunctions. METHODS: To study the hypothesis 11-12 month old aged wistar rats (n = 6) were administered cigarette smoke extract (CSE) through intraperitoneal route (0.5 ml/rat) twice a week for 2 months. Respiratory lung functions were measured through whole body plethysmography. Lung histopathological evaluation and neuronal degeneration were observed by using H&E, picrosirius red and nissl staining respectively. Motor function tests were done through panel of neuro-behavioral tests and protein expressions were performed in lung and brain tissue homogenates through western blotting. RESULTS: Sub-chronic CSE exposure worsened the lung functions including decreased tidal volume (p < 0.05), peak inspiratory flow (p < 0.05) and enhanced pause (p < 0.05). Grossly, solid neoplastic lesions were visible on the supra-lateral surface of the lungs of the CSE treated animals. Histopathological examination revealed immune cell infiltration, dominated with macrophages and alveolar type II cells stained positive for PCNA. Increased expression of BAX, PCNA, Wnt-3a, p-ß-catenin (p < 0.05) was seen in the lungs of CSE treated aged animals. Elevated expression of inflammatory markers including NF-ϏB, TNF-α, TNF-R1, p-AKT was found in CSE treated lung tissues. Moreover, our result showed increased MCP-1, VEGF and IL-6 levels in BALF and plasma (p < 0.01) which might lead to neo-vascularization and excessive cell proliferation in lungs of CSE induced rats. Sub-chronic cigarette smoke exposure retarded the motor activity with suppression of D1 and D2 receptor expression in brain tissues. Brain tissue revealed the abundance of hyperchromatic and pyknotic nuclei suggesting neuronal degeneration. CONCLUSION: So in conclusion, chronic cigarette smoking in old age creates susceptibility to fast onset of lung inflammatory diseases and neuro-motor retardation than their nonsmoker counterparts.

Yizhi Qingxin Formula Extract Ameliorates Cognitive Decline in Aged Rats via the Brain-Derived Neurotrophic Factor/Tropomyosin Receptor Kinase B Pathway.

Cognitive impairment and decline in old age are primarily driven by the accumulation of age-related neuropathologies, and old age is thus the primary risk factor for neurodegenerative diseases such as AD. Here, we investigated the effects of Yizhi Qingxin formula (YQF) extract on cognitive impairment in aged rats and determine the role of the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) pathway underlying the neuroprotective effects of the YQF extract. Fifty male Wistar rats were randomly divided into five groups: Control group, Model group, Donepezil group, and YQF extract groups (treatment with YQF extract at two different doses). After treatment with YQF extract for 8 weeks, learning and cognitive abilities were assessed using the Morris water maze. Morphological changes in the hippocampus were observed using hematoxylin-eosin. Activated microglia and astrocytes were assessed using immunohistochemistry. Expressions of proteins and genes were examined using western blotting and real-time PCR. The results revealed that oral treatment with YQF extract dramatically improved spatial learning and memory ability and ameliorated histopathological and morphological characteristics in aged rats. YQF extract significantly increased acetylcholine and interleukin (IL)-10 levels but markedly decreased amyloid-ß peptide, tumor necrosis factor alpha (TNFα), IL-2, and IL-6 levels. In addition, it inhibited the excessive activation of microglia and astrocytes, downregulated the expressions of TNFα and IL-2, and upregulated nerve growth factor, BDNF, and TrkB expressions. Furthermore, hippocampal extracellular signal-related kinase (Erk) and protein kinase B (Akt), the upstream signaling of BDNF/TrkB, were also activated by treatment with YQF extract. Our findings indicate that YQF extract activates the BDNF/TrkB pathway through the upregulation of Erk and Akt signaling, and the activated signaling pathway might contribute to the protective effects of YQF extract on cognitive impairment in aged rats.

[U-133, a heat shock proteins inducer, precludes sleep disturbances in a model of the preclinical stage of Parkinson's disease in aged rats.]

Parkinson's disease (PD) is a chronic progressive neurodegenerative disease, closely associated with aging. It is considered incurable due to both late diagnosis and symptomatic treatment, which is able to alter neither molecular mechanisms of sleep disruption nor the neurodegenerative processes, developing with aging and PD progression. In the present study, we assess the therapeutic potential of a novel chaperone inducer U-133 (acetyl 2,3,7-tris-O-glucoside echinochrome) in the preclinical stage of PD modelled in aged rats by the inhibition of the proteasomal system in the brain. U-133 is a derivative of the sea urchin pigment echinochrome (2,3,5,7,8-pentahydroxy-1,4-naphthoquinone) produced by glycosylation, which possesses neuroprotective, antioxidant, anticancer properties. The administration of U-133, inducing the synthesis of Hsp70i and Hdj1 heat shock proteins in the brain, precludes the increase of light sleep (drowsiness) stage and the decrease of deep slow-wave sleep total time, both occurring with the progression of the preclinical stage of PD modelled in aged Wistar rats. Deep slow-wave sleep is thought to promote glymphatic clearance and to accelerate protein synthesis. Thus, U-133-induced increase in deep slow-wave sleep percentage, as compared to the preclinical model, is considered having a neuroprotective effect that contributes to the intensification of the restorative function of neurons and counteracts the progressing neurodegeneration.

ALDH2 attenuates early-stage STZ-induced aged diabetic rats retinas damage via Sirt1/Nrf2 pathway.

AIMS: Acetaldehyde dehydrogenase 2 (ALDH2) was reported for its protective properties on myocardial damage, stroke and neurodegeneration disease, but the effects and mechanisms of ALDH2 in the modulation of diabetic retinopathy remain unclear. The present study evaluated the protection effects of ALDH2 on streptozocin (STZ)-induced aged diabetic rats retinas damage. MAIN METHODS: 24 aged male diabetic Sprague-Dawley (SD) rats induced by a single intraperitoneal injection of STZ were randomly divided into Alda1-treated group and dimethylsulfoxide (DMSO) group. Rats were intraperitoneally injected with 10 mg/kg ALDH2 activator Alda1 (or DMSO) 3 days before STZ injection and 30 days afterwards. A series of detections on retinal structural, functional and molecular levels were applied at 1 d, 7 d and 30 d after aged diabetic rats model established. KEY FINDINGS: Optical coherence tomography (OCT) revealed that the thickness of outer nuclear layer (ONL) and whole retinas in Alda1-treated group were thicker than DMSO group. Full field electroretinograms (ffERG) showed a higher amplitude wave (dark-adaptation 3.0 and OPs) in Alda1-treated group. In addition, the levels of retinal tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) from Alda1-treated group were lower whereas superoxide dismutase (SOD) activity was notably higher. Moreover, the expressions of ALDH2, silence information regulation factor 2 related enzyme I (Sirt1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in Alda1-treated group retinas were significantly increased, while the expression of vascular endothelial growth factor (VEGF-α) was dramatically decreased. SIGNIFICANCE: ALDH2 could ameliorate early-stage STZ-induced aged diabetic rats retinas damage possibly via increasing Sirt1 and Nrf2 expression.

Administrations of Preoperative Shenmai Injection and Postoperative Shenfu Injection, Two Ginseng Containing TCM Formulas, Improve Cognitive Dysfunction in Aged Rats.

Postoperative cognitive dysfunction (POCD) is one of the major complications in patients who have undergone surgeries. Reduction of surgery-induced inflammation and perioperative stress responses may prevent the development of POCD. As recent experimental data have suggested, Shenmai and Shenfu injections, two ginseng containing formulations, may improve cognition. We designed this study using aged rats as an experimental model to determine the effect of combined perioperative Shenmai injection and Shenfu injection in preventing the development of POCD and exploring the underlying mechanism of this intervention. Aged rats were randomized into one of the two groups. Rats in the experiment group received preoperative Shenmai injection and postoperative Shenfu injection while those of the control group did not receive this treatment. Study results indicate that the memory and cognitive ability of rats in the experiment group were significantly better than those of the control group at postoperative day 1 as well as at day 3. Plasma levels of neuron-specific enolase (NSE), S-100 [Formula: see text] protein, interleukin-6 (IL-6), tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), cortisol (COR), aldosterone (ALD), and adenocorticotropic hormone (ACTH) were significantly lower in the experiment group than in those of the control group (day 1 postoperatively). The plasma level of NSE on postoperative day 3 remained lower in the experimental group than in those of the control group. Our experimental results indicate that preoperative Shenmai and postoperative Shenfu injections facilitate conscious recovery and prevent postoperative cognitive decline. This anti-POCD effect may be a result of minimizing surgery-induced inflammation and reduction of perioperative stress responses by these injections.

Genistein and daidzein treatments differently affect uterine homeostasis in the ovary-intact middle-aged rats.

This study aimed to investigate the effects of soy isoflavones, genistein (GEN) and daidzein, (DAI) on the uterine function in ovary-intact middle-aged rats. GEN and DAI (35mg/kg) were subcutaneously administrated to acyclic (12-month-old) Wistar females, daily, for 4weeks. Control group received either vehicle (olive oil and ethanol, 9:1) or remained intact. We found that GEN and DAI differently affect uterine morphophysiology. GEN significantly increased the uterine wet weight which was associated with hyperplastic changes, revealed by stereological and histomorphometrical analyses. Also, PCNA immunoexpression was increased, whereas expression of apoptotic marker (caspase-3) was decreased. Protein and gene expressions of ERα were down-regulated, while PR and ERß were up-regulated after GEN application. Also, GEN caused an increase of LAC and VEGF mRNA expression, together with an up-regulation of Akt activity. In contrast, DAI did not change the uterine wet weight and stereological features of the main uterine compartments as well as LAC and VEGF gene expression. Absence of hyperplastic changes were illustrated by an increase in caspase-3 immunoexpression, associated with reduced PCNA expression. DAI up-regulated only the expression of ERß, while the expression levels of ERα and PR remain unaffected. Also, DAI inhibited the activation of Akt due to down-regulation of phosphorylated and total form of Akt protein expression. Compared to GEN, DAI did not promote events associated with the endometrial cell proliferation in the conducted study, figuring as the compound with a potential safety profile, which justifies further investigation.

Oral administration of Grifola frondosa polysaccharides improves memory impairment in aged rats via antioxidant action.

SCOPE: Grifola frondosa is an edible/medicinal mushroom with great nutritional value and bioactivity. The present study was performed to evaluate the beneficial effect of polysaccharides isolated from Grifola frondosa on memory impairment in aged rats. METHODS AND RESULTS: 20-month-old rats were gavaged with Grifola frondosa polysaccharides (GFP) for 8 weeks. Morris Water Maze test revealed that GFP administration significantly improved memory impairment in aged rats. GFP supply was also found to attenuate age-associated changes of brain histology and ultrastructure observed by light microscopy and transmission electron microscopy. Moreover, the increase of total antioxidant capacity (T-AOC), glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, catalase (CAT) activity, as well as the decreased nitric oxide (NO) and malondialdehyde (MDA) levels, were consistent with the behavioral results. CONCLUSION: These findings indicated that oral administration of GFP could improve memory impairment via antioxidant action, and dietary supplementation with GFP may provide potential benefits on brain aging.