β-hydroxybutyrate Alleviates Learning and Memory Impairment Through the SIRT1 Pathway in D-Galactose-Injured Mice

Learning and memory impairment is a common clinical symptom of aging and nervous system injuries, and seriously affects quality of life. Memory impairment is associated with increased oxidative stress (OS) and inflammatory response. β-hydroxybutyrate (BHBA) is a water-soluble endogenous small-molecule ketone body that easily crosses the blood-brain barrier and has shown neuroprotection activities. In this study, we investigated the effects and mechanisms of BHBA on D-galactose (D-gal)-induced memory impairment in mice by in vitro and in vivo experiments. BHBA was administered intragastrically to D-gal-injured C57BL/6 mice for 42 days. Water maze performance, the morphology of the hippocampus with Nissl staining, the ACh content, OS, and inflammation status were examined. To further investigate the mechanism, hippocampal neuronal cells (HT22) were treated with BHBA with or without the SIRT1 inhibitor or small interfering RNAs against sirt1 (si-SIRT1) before incubation with D-gal. BHBA significantly improved water maze performance; increased the ACh content, SOD activity, and SIRT1 expression; and decreased AChE and LDH activity, ROS, MDA, IL-1β, TNF-α contents, and NLRP3 expression. Further studies with the SIRT inhibitor or siRNAs against sirt1 reversed the above effects of BHBA. Collectively, BHBA inhibited hippocampal OS and the inflammation process to alleviate learning and memory impairment through activating the SIRT1 pathway in D-gal-injured mice, suggesting that BHBA could be a potential option for drug development of learning and memory impairment induced by nervous system injuries.

Download Full-text

Ferroptosis contributes to isoflurane-induced neurotoxicity and learning and memory impairment

Cell Death Discovery ◽

10.1038/s41420-021-00454-8 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Pengfei Liu ◽

Jing Yuan ◽

Yetong Feng ◽

Xin Chen ◽

Guangsuo Wang ◽

...

Keyword(s):

Cell Death ◽

Learning And Memory ◽

Memory Impairment ◽

Close Association ◽

Dimethyl Fumarate ◽

Dependent Manner ◽

Transport Chain ◽

The Relationship

AbstractFerroptosis is a novel type of programmed cell death, which is different from apoptosis and autophagic cell death. Recently, ferroptosis has been indicated to contribute to the in vitro neurotoxicity induced by isoflurane, which is one of the most common anesthetics in clinic. However, the in vivo position of ferroptosis in isoflurane-induced neurotoxicity as well as learning and memory impairment remains unclear. In this study, we mainly explored the relationship between ferroptosis and isoflurane-induced learning and memory, as well as the therapeutic methods in mouse model. Our results indicated that isoflurane induced the ferroptosis in a dose-dependent and time-dependent manner in hippocampus, the organ related with learning and memory ability. In addition, the activity of cytochrome c oxidase/Complex IV in mitochondrial electron transport chain (ETC) was increased by isoflurane, which might further contributed to cysteine deprivation-induced ferroptosis caused by isoflurane exposure. More importantly, isoflurane-induced ferroptosis could be rescued by both ferroptosis inhibitor (ferrostatin-1) and mitochondria activator (dimethyl fumarate), which also showed effective therapeutic action against isoflurane-induced learning and memory impairment. Taken together, our data indicate the close association among ferroptosis, mitochondria and isoflurane, and provide a novel insight into the therapy mode against isoflurane-induced learning and memory impairment.

Download Full-text

Cognitive-Enhancing Effect ofAronia melanocarpaExtract against Memory Impairment Induced by Scopolamine in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/6145926 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Hyeon Yong Lee ◽

Jin Bae Weon ◽

Youn Sik Jung ◽

Nam Young Kim ◽

Myong Ki Kim ◽

...

Keyword(s):

Passive Avoidance ◽

Learning And Memory ◽

Morris Water Maze ◽

Water Maze ◽

Memory Impairment ◽

Ache Activity ◽

Antioxidant Effect ◽

Enhancing Effect ◽

Aronia Melanocarpa ◽

Avoidance Tests

Aronia melanocarpa(A. melanocarpa)berriesare a fruit with a marked antioxidant effect. The objective of this study was to confirm the effect ofA. melanocarpa berriesextract against scopolamine-induced memory impairment in mice using the Morris water maze and passive avoidance test. Moreover, we determined a possible mechanism of the cognitive-enhancing effect involving AChE activity and BDNF and p-CREB expression in the hippocampus of mice.A. melanocarpa berriesextract attenuated the learning and memory impairment induced by scopolamine in the Morris water maze (79.3 ± 0.8 s of 200 mg/kg and 64.4 ± 10.7 s of 400 mg/kg on day 4) and passive avoidance tests (46.0 ± 41.1 s of 200 mg/kg and 25.6 ± 18.7 s of 400 mg/kg).A. melanocarpa berriesextract reduced the acetylcholinesterase level in the hippocampus of scopolamine-injected mice and increased BDNF and p-CREB expression in the hippocampus. The major compound, cyanidin-3-O-galactoside, also reversed memory impairment. These results showed thatA. melanocarpa berriesextract improved memory impairment by inhibiting AChE and increasing BDNF and p-CREB expression, and cyanidin-3-O-galactoside may be responsible for the effect ofA. melanocarpa berriesextract.

Download Full-text

Water Soluble Pleurotus ostreatus Polysaccharide Down-Regulates the Expression of MMP-2 and MMP-9 in Caco-2 Cells

Notulae Botanicae Horti Agrobotanici Cluj-Napoca ◽

10.15835/nbha4129305 ◽

2013 ◽

Vol 41 (2) ◽

pp. 553

Author(s):

Sabina COJOCARU ◽

Mihaela RADU ◽

Liviu Gabriel BODEA ◽

Mirela Mihaela CIMPEANU ◽

Gogu GHEORGHITA ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Protein Complexes ◽

Gelatin Zymography ◽

Water Soluble ◽

Colon Cancer Cells ◽

Sod Activity ◽

Kinetic Measurements ◽

The Third

Many polysaccharides and polysaccharide-protein complexes isolated from mushrooms have immunomodulatory and anti-cancer effects. Our aim was to study the regulatory mechanisms of Caco-2 cell response to water soluble P. ostreatus polysaccharide extract up to 72 hours. Specific enzymatic activities were assessed by kinetic measurements. The reduced glutathione content and the lipid peroxidation level were also analyzed. Protein expression of several heat shock proteins, Bcl-2 and metalloproteinases 2 and 9 were revealed by Western blot. Gelatin zymography assay was used to evaluate the MMP-2 and MMP-9 activities. Until the third day of exposure the total SOD activity decreased continuously by 30%, whereas GST and GR ones diminished by 17% respectively 30.5% compared to control. No significant changes were observed in CAT and G6PDH specific activities as well as in GSH and MDA concentration. After the third day of exposure a significant up-regulation of Hsp60 and Hsp90 expression and a down-regulation of Hsp70 one were registered. Bcl-2 protein levels were down-regulated by 50% in the first day of treatment but increased after 3 days. MMP-2 and 9 secretion in the culture medium was significantly reduced suggesting a diminished ability of invasion of colon cancer cells. Our data revealed that in vitro treatment with P. ostreatus aqueous polysaccharide extract does not induce apoptosis in Caco-2 cell line but it could inhibit the invasion of colon cancer cells through the basement membrane.

Download Full-text

The activity of superoxide-dismutase in animal cell culture CHO-K1 after treatment with fullerenol and mytomicine C

Hemijska industrija ◽

10.2298/hemind0903143b ◽

2009 ◽

Vol 63 (3) ◽

pp. 143-149 ◽

Cited By ~ 1

Author(s):

Visnja Bogdanovic ◽

Marija Slavic ◽

Jasminka Mrdjanovic ◽

Slavica Solajic ◽

Aleksandar Djordjevic

Keyword(s):

Superoxide Dismutase ◽

Mammalian Cells ◽

Animal Cell ◽

Water Soluble ◽

Cytotoxic Agents ◽

Antioxidant Defenses ◽

Free Radical Scavengers ◽

Sod Activity

Eukaryotic cell survives in predominantly reduced conditions. Homeostasis of cellular redox system is an imperative of cell surviving and its normal metabolism. ROS are well recognized for playing a dual role as both deleterious and beneficial species, since they can be either harmful or beneficial to living systems. These species are mutagenic compounds known to lead to DNA damage, favor cell transformation, and contribute to the development of a variety of malignant diseases. All the effects of oxidants are influenced by the cellular antioxidant defenses. This multilayer system consists of low molecular weight components and several antioxidant enzymes. Superoxide dismutases (SODs) are the only enzymes dismuting superoxide radicals. Mitomycin C, a cross-linking agent, demonstrated genotoxicity in all in vitro and in vivo test systems in mammalian cells and animals. Water-soluble fullerenes are well known as cytotoxic agents for many cell lines in vitro. At the other side, fullerenols are good free radical scavengers and antioxidants both in vitro and in vivo. This paper investigates the effects of fullerenol on survival and fullerenol/ /mytomicine (MMC) treatment on superoxide-dismutase (SOD) activity in CHO-K1 cells. Samples were treated 3 and 24 h with fullerenol (C60(OH)24) at concentration range 0.01-0.5 mg/mL and survival was monitored with dye exclusion test (DET). The activity of total SOD was estimated in samples treated with chosen concentrations of fullerenol and MMC (0.5 and 0.1 mg/mL) after 3 and 24 h of cell incubation. Increasing of C60(OH)24 concentration leads to decreasing of percent of surviving cells 3 and 24 h after incubation. The activity of total SOD enhanced with higher concentration of fullerenol, while decreased in the highest concentration at both experimental points. In samples treated with MMC, as well as in samples treated with fullerenol (0.0625 mg/mL) + MMC was noticed boost in total SOD activity in comparison with controls. Treatment with fullerenol decreased SOD activity in rest of samples treated with MMC. Decreased activity of superoxide-dismutase in almost all samples treated with fullerenol and MMC might be contributed to antioxidative properties of fullerenol. Increased enzyme level at concentration of 0.0625 mg/mL may be due to its prooxidative activity.

Download Full-text

Soybean Isoflavones Influences Learning and Memory and Caspase-3 Levels in the Hippocampus of Rats after MWM Test

Applied Mechanics and Materials ◽

10.4028/www.scientific.net/amm.411-414.3178 ◽

2013 ◽

Vol 411-414 ◽

pp. 3178-3180

Author(s):

Li Hai Jin ◽

Xing Yu Zhao ◽

Wei Zhang ◽

Wei Chen ◽

Guo Qing Sun ◽

...

Keyword(s):

Learning And Memory ◽

Morris Water Maze ◽

Water Maze ◽

Memory Impairment ◽

Caspase 3 ◽

Morris Water Maze Test ◽

Once Daily ◽

Soybean Isoflavones ◽

Maze Test ◽

Intermediate Dose

We assessed the effectiveness and mechanism of action of Soybean Isoflavones on learning and memory and Caspase-3 levels in the hippocampus of rats after Morris water maze (MWM test). Soybean Isoflavones (200,400 or 800 mg/kg/d) were administered by intragavage once daily for 14 consecutive days. The Morris water maze test was used to evaluate the ability of Soybean Isoflavones to increase learning and memory impairment. The levels of Caspase-3 in hippocampus of rats were detected by Westernblot after MWM test. Compared to untreated controls (P<0.01), MWM could be prolonged after Soybean Isoflavones treatment (P<0.05 for="" low="" and="" intermediate="" dose="" groups="" westernblot="" analysis="" showed="" that="" the="" protein="" expression="" of="" caspase-3="" was="" decreased="" in="" different="" concentration="" soybean="" isoflavones="" i="">P<0.05 and="" i="">P<0.01, respectively). The results suggest that Soybean Isoflavones is effective in improving the learning and memory in rats , the mechanism of which may be related Caspase ways.

Download Full-text

Seminal vesicle response to androgen with adrenaline, noradrenaline and acetylcholine

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1960.198.1.15 ◽

1960 ◽

Vol 198 (1) ◽

pp. 15-20 ◽

Cited By ~ 10

Author(s):

Jerome A. Grunt ◽

James T. Higgins

Keyword(s):

Nervous System ◽

Autonomic Nervous System ◽

Seminal Vesicle ◽

Testosterone Propionate ◽

Water Soluble ◽

Muscle System ◽

Motor End Plate ◽

Organ Response ◽

Spontaneous Contractions

In a study of the end-organ response to androgen, use has been made of the seminal vesicle of the rat. Observations were made of the in vitro spontaneous contractions and responses to autonomic stimulating drugs. Vesicles of castrated rats contract spontaneously in vitro. Testosterone propionate given to the rat before sacrifice inhibits contractions, as does injection of water-soluble androgen into the in vitro chamber. Vesicles of castrates have lower thresholds to adrenaline and possibly to acetylcholine, but not to noradrenaline. The thresholds to acetylcholine but not to noradrenaline are elevated after injection of water-soluble androgen into the in vitro chamber. Several interpretations are discussed. Androgen and the autonomic nervous system probably interact at or near the cell membrane of the vesicle musculature. The three drugs tested most likely act at different loci along the nerve—motor end plate—muscle system, and noradrenaline is probably not a primary mediating agent of spontaneous contractions of the vesicle of the castrated rat.

Download Full-text

Lanthanum chloride induces autophagy in rat hippocampus through ROS-mediated JNK and AKT/mTOR signaling pathways

Metallomics ◽

10.1039/c8mt00295a ◽

2019 ◽

Vol 11 (2) ◽

pp. 439-453 ◽

Cited By ~ 4

Author(s):

Xiang Gao ◽

Jinghua Yang ◽

Yingqi Li ◽

Miao Yu ◽

Shiyu Liu ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Signaling Pathways ◽

Learning And Memory ◽

Memory Impairment ◽

Mtor Signaling ◽

Lanthanum Chloride ◽

Rat Hippocampus ◽

Central Nervous System Damage

Lanthanum (La) can cause central nervous system damage in rats and lead to learning and memory impairment, but the relevant mechanisms have not been fully elucidated.

Download Full-text

PHARMACOLOGICAL EVALUATION OF TRIPHALA CHURNA INSTREPTOZOTOCIN (I. C. V.) INDUCED DEMENTIA IN RATS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2018v10i3.22795 ◽

2018 ◽

Vol 10 (3) ◽

pp. 97

Author(s):

Purabi Deka ◽

Arun Kumar

Keyword(s):

Lipid Peroxidation ◽

Superoxide Dismutase ◽

Learning And Memory ◽

Morris Water Maze ◽

Water Maze ◽

Memory Impairment ◽

Treated Group ◽

Control Group ◽

Standard Group ◽

Glutathione Level

Objective: The objective of the study was to investigate the memory improving activity of Triphala Churna hydro-methanolic fruit extract on learning and memory functions in Streptozotocin (I. C. V) induced dementia in rats by using morris water maze and elevated plus maze.Methods: A total of 42 albino wistar rats weighing 80-100 g were randomized into 7 equal groups as follows: Normal control group received normal saline (1 ml/kg p. o.) for 24 d, STZ treated group (3 mg/kg, i. c. v) were administered in two dosage regimen i.e. on first day and third day.), Standard group: Streptozotocin (3 mg/kg i. c. v)+Vitamin E (100 mg/kg/day p. o.) were administered for 21 d, Standard group: Streptozotocin (3 mg/kg i. c. v)+Rivastigmine (2 mg/kg/day p. o.) were administered for 21 d. The learning and memory-impaired rats were treated with Triphala Churna Formulation 1, Triphala Churna Formulation 2 and Triphala Churna Formulation 3 for 21 d (100 mg/kg p. o.). AchE activity, lipid peroxidation, superoxide dismutase, glutathione level of brain homogenate was estimated in Control/STZ (I. C. V)/Standard/Triphala Churna fruits extract treated rats.Results: Administration of Triphala Churna fruits extract significantly restored learning and memory impairment induced by STZ (I. C. V) in the elevated plus maze and morris water maze. Furthermore, in the TPLC F2 and TPLC F3 treated group brain AchE level was decreased (P≤0.01) as well as brain lipid peroxidation was also decreased (P≤0.001). Brain antioxidant enzymes such as glutathione level were increased (P≤0.001) in the TPLC1 and TPLC2 treated group when compared to the STZ treated group, TPLC F2 and TPLC F3 treated group showed significant (P≤0.001, P≤0.01) increase in superoxide dismutase level. Conclusion: Triphala Churna fruits extract has an improving effect on learning and memory impairment rats produced by Streptozotocin (I. C. V) and may have a useful effect in the treatment of dementia and Alzheimer's disease.

Download Full-text

Ginkgolide B Alleviates Learning and Memory Impairment in Rats With Vascular Dementia by Reducing Neuroinflammation via Regulating NF-κB Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2021.676392 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lijuan Huang ◽

Yijie Shi ◽

Liang Zhao

Keyword(s):

Vascular Dementia ◽

Learning And Memory ◽

Memory Impairment ◽

Cognitive Learning ◽

Glucose Deprivation ◽

Potential Effect ◽

Learning Ability ◽

Inflammatory Factors ◽

Sprague Dawley ◽

Nissl Staining

Ginkgobalide B (GB) as the main active ingredient of traditional Chinese medicine Ginkgo biloba extract is reported to reduce neuroinflammation, protect neurons and promote cognitive learning ability. To explore that GB can reduce neuroinflammation through regulating nuclear factor-kappaB (NF-κB) signaling pathway and overcome cognitive dysfunction in rats with vascular dementia (VD), we aim at investigating the potential effect of GB on enhancing cognitive function in rats with VD. It was found that GB improved survival of oxygen-glucose deprivation (OGD) treated SH-SY5Y cells by attenuating inflammatory response via Toll-like Receptor 4 (TLR4)/NF-κB pathway. When rats were treated with bilateral common carotid artery occlusion (BCCAO) for 24 h, saline and GB were administered in Sprague-Dawley (SD) rats via a single intraperitoneal injection for consecutive 14 days. The behavioral changes of VD like rats treated with GB were observed through open field test, Morris water maze (MWM) and Y-maze electric maze. Nissl staining and immunofluorescence were used to observe changes of neurons in the hippocampus of rats. Western blot analysis was performed by detecting NF-κB pathway related inflammatory factors. The results found that GB can significantly improve the learning and memory ability of VD rats by reducing TLR4/NF-κB mediated neuroinflammation. In conclusion, GB seemed to be a potential drug for amelioration of learning and memory impairment in rats with VD.

Download Full-text