BIOCHEMICAL GENETICS
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2022
·Vol. 61
·期 3
·916-930
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IF 2.22
Wang Pengwei,Mao Senlin,Yi Tingting,Wang Lihua
Vascular dementia (VaD) is the second most common subtype of dementia, but the precise mechanism underlying VaD is not fully understood. Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) can act as a key regulator in physiological and pathological processes, including neurological disorders, but whether it is correlated with VaD has not been elucidated. In this study, we established a mouse model of VaD by the transient bilateral common carotid artery occlusion surgery. As expected, the Morris water maze showed that VaD mice had significant deficits in spatial learning and memory. MALAT1 was elevated in the hippocampus of VaD mice. Additionally, we found that microRNA (miR)-9-3p was downregulated in the VaD hippocampus. By performing a dual-luciferase report assay, we verified the binding relationship between MALAT1 and miR-9-3p. Interestingly, synapse-associated protein-97 (SAP97), a well-known gene related to synaptic functions, was found upregulated in the hippocampus of VaD mice. In vitro experiments performed on hippocampal neurons demonstrated that miR-9-3p negatively regulated SAP97 expression. The downregulation of MALAT1 in hippocampal neurons increased miR-9-3p and reduced SAP97, whereas miR-9-3p inhibition rescued the MALAT1 downregulation-mediated SAP97 reduction. In conclusion, the present study reported the alterations in the expression levels of MALAT1, miR-9-3p, and SAP97 in the hippocampus of VaD mice, suggesting that MALAT1 targets miR-9-3p to upregulate SAP97 in the hippocampus of mice with VaD. This work will be helpful for understanding the molecular mechanisms of VaD.
研究领域:
神经科学
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分子生物学
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病理学
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DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2024
·
IF 4.6
Xiong Zhonghua,Deng Jiahui,Xie Pandeng,Tang Chongyang,Wang Jing,Deng Qinqin,Yang Yujiao,Zhang Jing,Guo Mengyi,Wang Xiongfei,Guan Yuguang,Luan Guoming,Zhou Jian,Li Tianfu
Deep brain stimulation (DBS) of the anterior nucleus of the thalamus is an efficacious treatment option for patients with refractory epilepsy. Our previous study demonstrates that adenosine is a potential target of DBS for the treatment of epilepsy. Equilibrative nucleoside transporters-1 (ENT1) and ectonucleotidases (CD39, CD73) function as regulators of extracellular adenosine in the brain. It is unclear whether ENT1, CD39, and CD73 are involved in the mechanism of DBS for epilepsy. A total of 48 SD male rats were divided into four groups: control (naïve rats), Pilo (pilocarpine induced rats with epilepsy), DBS (rats with epilepsy treated with DBS for 8 weeks), and sham. In the present study, video electroencephalogram monitoring, Morris water maze assays, in vivo measurements of adenosine using fiber photometry, histochemistry, and western blot were performed on the hippocampus. DBS markedly attenuated spontaneous recurrent seizures (SRSs) and enhanced spatial learning in rats with epilepsy, assessed through video-EEG and water maze assays. Fibred photometry measurements of an adenosine sensor revealed dynamic increase in extracellular adenosine during DBS. The expressions of ENT1, CD39, and CD73 in Pilo group and sham group increased compared with the control group, while the expressions of ENT1, CD39, and CD73 in DBS group decreased compared to that of Pilo group and sham group. The findings indicate that DBS reduces the number of SRSs and improves spatial memory in rats with epilepsy with concomitant decrease of ENT1, CD39, and CD73 expressions. Adenosine-modulating enzymes might be the potential targets of DBS for the treatment of epilepsy.
研究领域:
神经科学
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药理学
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癫痫学
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神经病学
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产品关联
DOI
PubMed
高影响因子
Journal of Neuroinflammation
·
2018
·Vol. 15
·期 1
·1-12
·
IF 5.193
Gao Bo,Wu Yu,Yang Yuan-Jian,Li Wei-Zu,Dong Kun,Zhou Jun,Yin Yan-Yan,Huang Da-Ke,Wu Wen-Ning
Background Epilepsy is a common neurological disorder and is not well controlled by available antiepileptic drugs (AEDs). Inflammation is considered to be a critical factor in the pathophysiology of epilepsy. Sinomenine (SN), a bioactive alkaloid with anti-inflammatory effect, exerts neuroprotective activity in many nervous system diseases. However, little is known about the effect of SN on epilepsy.Methods The chronic epilepsy model was established by pentylenetetrazole (PTZ) kindling. Morris water maze (MWM) was used to test spatial learning and memory ability. H.E. staining and Hoechst 33258 staining were used to evaluate hippocampal neuronal damage. The expression of nucleotide oligomerization domain (NOD)-like receptor protein 1 (NLRP1) inflammasome complexes and the level of inflammatory cytokines were determined by western blot, quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA) kits.Results SN (20, 40, and 80 mg/kg) dose-dependently disrupts the kindling acquisition process, which decreases the seizure scores and the incidence of fully kindling. SN also increases the latency of seizure and decreases the duration of seizure in fully kindled rats. In addition, different doses of SN block the hippocampal neuronal damage and minimize the impairment of spatial learning and memory in PTZ kindled rats. Finally, PTZ kindling increases the expression of NLRP1 inflammasome complexes and the levels of inflammatory cytokines IL-1β, IL-18, IL-6, and TNF-α, which are all attenuated by SN in a dose- dependent manner.Conclusion sSN exerts anticonvulsant and neuroprotective activity in PTZ kindling model of epilepsy. Disrupting the kindling acquisition, which inhibits NLRP1 inflammasome-mediated inflammatory process, might be involved in its effects.
研究领域:
神经病学
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药理学
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炎症研究
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DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2023
·
IF 5.1
Guo Xiying,Lei Min,Ma Guandi,Ouyang Changhan,Yang Xiaosong,Liu Chao,Chen Qingjie,Liu Xiufen
Clinical and epidemiological research shows that people with diabetes mellitus frequently experience diabetic cognitive impairment. Schisandrin A (SchA), one of the lignans found in the dried fruit of Schisandra chinensis, has a variety of pharmacological effects on immune system control, apoptosis suppression, anti-oxidation and anti-inflammation. The goal of the current investigation was to clarify the probable neuro-protective effects of SchA against streptozotocin-induced diabetes deficiencies of the spatial learning and memory in rats. The outcomes show that SchA therapy effectively improved impaired glucose tolerance, fasting blood glucose level and serum insulin level in diabetic rats. Additionally, in the Morris water maze test, diabetic rats showed deficits in spatial learning and memory that were ameliorated by SchA treatment. Moreover, giving diabetic rats SchA reduced damage to the hippocampus structure and increased the production of synaptic proteins. Further research revealed that SchA therapy reduced diabetic-induced hippocampus neuron damage and the generation of Aβ, as demonstrated by the upregulated phosphorylation levels of insulin signaling pathway connected proteins and by the decreased expression levels of inflammatory-related factors. Collectively, these results suggested that SchA could improve diabetes-related impairments in spatial learning and memory, presumably by reducing inflammatory responses and regulating the insulin signaling system.
研究领域:
神经科学
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药理学
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内分泌学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2022
·Vol. 60
·期 2
·524-544
·
IF 5.682
Wu Mengyu,Liao Wenli,Zhang Ruyi,Gao Yuting,Chen Tao,Hua Liangliang,Cai Fei
Accumulating clinical and epidemiological studies indicate that learning and memory impairment is more prevalent among people with diabetes mellitus (DM). PTP1B is a member of protein tyrosine phosphatase family and participates in a variety of pathophysiological effects including inflammatory, insulin signaling pathway, and learning and memory. This study was aimed to investigate the effects of CA, a specific inhibitor of PTP1B, on spatial learning and memory impairment in diabetic mice caused by high-fat diet and injection of streptozotocin. We found that the protein expressions of PTP1B increased in hippocampal CA1, CA3, and PFC regions of diabetic mice. Network pharmacology results showed that PTP1B might be one of the key targets between diabetes and cognitive dysfunction, and CA might alleviate DM-induced cognitive dysfunction. Animal experiments showed that CA ameliorated DM-induced spatial learning and memory impairment, and improved glucose and lipid metabolic disorders. Moreover, administration of CA alleviated hippocampal structure damage and enhanced the expressions of synaptic proteins, including PSD-95, SYN-1, and SYP in diabetic mice. Furthermore, CA treatment not only significantly down-regulated the expressions of PTP1B and NLRP3 inflammatory related proteins (NLRP3, ASC, Caspase-1, COX-2, IL-1β, and TNF-α), but also significantly up-regulated the expressions of insulin signaling pathway–related proteins (p-IRS1, p-PI3K, p-AKT, and p-GSK-3β) in diabetic mice. Taken together, these results suggested that PTP1B might be a targeted strategy to rescue learning and memory deficits in DM, possibly through inhibition of NLRP3 inflammasome and regulation of insulin signaling pathway.
研究领域:
药理学
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神经科学
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内分泌学
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糖尿病研究
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认知科学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2017
·Vol. 9
·期 1
·371-378
·
IF 3.247
Yan Zhang,Li-Hong Zhang,Xi Chen,Ning Zhang,Guang Li
Aging is a complex process that is accompanied by neurological damage. Chronic injection of D-galactose (D-gal) can accelerate the aging process similar to natural aging and is commonly used to build an aging model to investigate aging. In the present study, the effects of piceatannol on D-gal-induced aging in mice were evaluated. Piceatannol treatment showed an observable anti-aging effect. Results obtained in vivo showed that piceatannol retained spontaneous motor activity and enhanced spatial learning and memory abilities in mice in which aging was induced by D-gal. Morphometric analysis displayed that piceatannol prevented D-gal-induced neuronal loss, increased the number of Nissl bodies, and promoted cell proliferation in the hippocampus and cortex. Piceatannol also significantly decreased the level of MDA and elevated SOD and CAT activity in the hippocampal and cortical tissues. Furthermore, western blotting results revealed that piceatannol treatment noticeably reversed the suppression of Nrf2 nuclear translocation and increased the expressions of HO-1 and NOQ1 in mice with aging induced by D-gal. Furthermore, piceatannol activated the Nrf2 pathway in natural aging mice, whereas treatment with the Nrf2 inhibitor brusatol reversed the increased expressions of Nrf2, HO-1, and NOQ1. In conclusion, treatment with piceatannol ameliorates behavioral disorder and brain injury in an aging mouse model; this suggests that piceatannol is a promising pharmaceutical candidate for the treatment of age-associated diseases.
研究领域:
老年学
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神经科学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Ziqi Gu,Hang Zhao,Yilan Song,Yiduo Kou,Wanting Yang,Ye Li,Xiang Li,Ling Ding,Zihui Sun,Jing Lin,Qi Wang,Xi Li,Xu Yang,Xuerong Huang,Chuang Yang,Zhiqian Tong
Alzheimer’s disease (AD), which is a prevailing type of dementia, presents a significant global health concern. The current therapies do not meet clinical expectations. Amyloid-beta (Aβ) has been found to induce endogenous formaldehyde (FA) accumulation by inactivating FA dehydrogenase (FDH); in turn, excessive FA triggers Aβ aggregation that eventually leads to AD onset. Hence, scavenging FA by astaxanthin (ATX, a strong exogenous antioxidant) may be pursued as a promising disease-modifying approach. Here, we report that liposomal nanoparticles coupled with PEG (PEG-ATX@NPs) could enhance water-solubility of ATX and alleviate cognitive impairments by scavenging FA and reducing Aβ deposition. To enable drug delivery to the brain, liposomes were used to encapsulate ATX and then coupled with PEG, which produced liposomal nanoparticles (PEGATX@NPs) with a diameter of <100 nm. The PEG-ATX@NPs reduced Aβ neurotoxicity by both degrading FA and reducing FA-induced Aβ assembly in vitro. Intraperitoneal administration of PEG-ATX@NPs in APPswe/PS1dE9 mice (APP/PS1, a familial model of AD), not only decreased the levels of brain FA and malondialdehyde (MDA, a typical product of oxidative stress), but also attenuated both intracellular Aβ oligomerization and extracellular Aβ-related senile plaque (SP) formation. These pathological changes were accompanied by rescued ability of spatial learning and memory. Collectively, PEG-ATX@NPs improved the water-solubility, bioavailability, and effectiveness of ATX. Thus, it has the potential to be developed as a safe and effective strategy for treating AD.
研究领域:
神经科学
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药理学
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纳米技术
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痴呆症研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Caiyun Li,Dingwei Zheng,Tianle Zhang,Siyuan Qian,Xinyao Liu,Zhengfu Yang,Kean-Jin Lim,Weihong Min,Jianqin Huang,Yiyi Yang,Zhengjia Wang
Cognitive decline associated with aging and neuroinflammation has been linked to gut microbiota dysbiosis and systemic inflammation, potentially mediated through the gut–brain axis. Bioactive peptides have shown potential as therapeutic candidates for neurodegenerative and neuroinflammatory disorders. While the walnut-derived peptide EVSGPGYSPN (EV-10) has demonstrated cognitive benefits, the therapeutic potential of its recombinant form, recombinant walnut-derived peptide (rWDP), expressed and purified from an Escherichia coli system, remains to be fully characterized. In this study, behavioral assessment using the Morris water maze revealed that rWDP significantly improved spatial learning and memory in d-galactose-induced aging mice. rWDP treatment was associated with changes in gut microbiota composition, including an increase in Akkermansia muciniphila and improvements in colon mucosal integrity. Systemic inflammation appeared to be attenuated, with reduced levels of IFN-γ and VCAM-1 and normalization of G-CSF and CXCL1 levels. In the brain, rWDP was associated with reduced microglial activation and preservation of hippocampal neuronal architecture. Notably, decreased p21 expression was observed in the hippocampus and cortex. In vitro, rWDP suppressed LPS-induced nitric oxide production and attenuated the expression of proinflammatory genes in BV2 microglial cells. Metabolomic analysis suggested a restoration of neurotransmitter homeostasis following rWDP treatment, with increased levels of 5-hydroxyindoleacetic acid, kynurenine, and glutathione observed. Overall, rWDP may alleviate cognitive deficits through multifaceted pathways involving the gut–brain axis and immune modulation, warranting further mechanistic investigation.
研究领域:
神经科学
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生物化学
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微生物学
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免疫学
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药理学
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衰老研究
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代谢组学
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产品关联
DOI
PubMed
高影响因子
ACTA HISTOCHEMICA
·
2019
·
IF 1.719
Yang Wang,Chun Wang,Yue Zhang,Guan Wang,Haitao Yang
Sevoflurane is a widely used inhaled anesthetic , which triggers neuroapoptosis and oxidative damage in the developing central nervous system and cognitive dysfunction later in life. However, no effective therapeutic strategy for sevoflurane-induced deleterious effects is well developed. The purpose of the present study was to explore whether luteoline could attenuate neonatal sevoflurane exposure-triggered neurotoxicity . In this study, six-day-old C57BL/6 mice were pretreated with luteoline (30, 60 mg/kg) intraperitoneally for 30 min before exposed to 3% sevoflurane 6 h consecutively. We first examined the effects of luteoline on hippocampal neuron apoptosis, inflammation and oxidative stress 18 h post anesthesia. The spatial learning and memory performance was measured using Morris water maze test from postnatal day 31 to 38. The results showed that luteoline ameliorated neuronal apoptosis as evidenced by decrease of apoptotic cells, downregulation of the cleavage levels of caspase-3 and PRAP, and inactivation of caspase-3. Moreover, luteoline significantly decreased protein expressions of inflammatory cytokines (IL-1β, IL-18 and TNF-α), inhibited NF-кB/NLRP3 pathway (NF-кB, NLRP3 , ASC and caspase-1) and suppressed NF-кB activity. Our analyses indicated that luteoline had a significant effect on decreasing the contents of ROS and MDA , elevating the activity of SOD, and ultimately improving spatial learning and memory deficits of mice. In summary, our findings confirm that the attenuation of luteoline on sevoflurane-induced spatial learning and memory impairment later is associated with inhibition of hippocampal neuron apoptosis, inflammation and oxidative stress early. Luteoline might be a potential therapeutic for sevoflurane anesthesia-induced neurobehavioral dysfunction.
研究领域:
药理学
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神经科学
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麻醉学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENT INTERNATIONAL
·
2023
·
IF 11.8
Tingting Ku,Yutong Liu,Yuanyuan Xie,Jindong Hu,Yanwen Hou,Xin Tan,Xia Ning,Guangke Li,Nan Sang
Tebuconazole, one of the most widely used triazole fungicides, is reported to potentially pose a risk of inducing neurological disorders in human beings. Considering the increasing exposure, whether it could influence cognitive function remains to be elucidated. Herein, we used a mouse model to evaluate the potential cognitive risks and possible mechanisms from the continuous edible application of tebuconazole at low concentrations. Our study revealed that tebuconazole deteriorated spatial learning and memory and downregulated the expression of glutamate receptor subunits. Importantly, metagenomic analysis indicated that tebuconazole not only led to significant shifts in the composition and diversity of the gut microbiota but also changed intestinal homeostasis. Specifically, after exposure, tebuconazole circulated in the bloodstream and largely entered the gut–brain axis for disruption, including disturbing the Firmicutes/Bacteroidetes ratio, interrelated neurotransmitters and systemic immune factors. Moreover, pretreatment with probiotics improved immune factor expression and restored the deterioration of synaptic function and spatial learning and memory. The current study provides novel insights concerning perturbations of the gut microbiome and its functions as a potential new mechanism by which tebuconazole exposes cognitive function-related human health.
研究领域:
神经科学
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微生物学
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药理学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Materials Today Communications
·
2021
·
IF 3.383
Qifeng Li,Yalong Gao,Jun Shen,Xiaoyu Mu,Junying Wang,Lufei Ouyang,Ke Chen,Hua He,Jiahui Pei,Qinjuan Ren,Si Sun,Haile Liu,Lei Zhou,Yuanming Sun,Wei Long,Jianning Zhang,Xiao-Dong Zhang
Hypoxemia as one of the most common symptoms of traumatic brain injury (TBI) can significantly exacerbate the development of secondary damage, which further contributes to generating large numbers of neurotoxic factors such as reactive oxygen and nitrogen species (RONS), pro-inflammatory cytokine and chemokine. Here, we developed a kind of quantum dots as catalase-mimic and multiple free radical scavengers by means of the microwave heating polymerization of l -lysine. Hydrogen peroxide as overproduced radicals can be decomposed to supply oxygen, contributing to improving the hypoxic condition in brain. Simultaneously, other traditional RONS such as O 2 − , OH, NO and ONOO − can be eliminated by the quantum dots. The total ROS level is back to normal after the quantum dots treatment, promoting the H 2 O 2 /LPS-stimulated cell survival in vitro . Oxidative stress induced by hypoxic brain injury is restored by the quantum dots intravenous injection, leading to the protection of neural cells in vivo . Additionally, the quantum dots can improve the spatial learning and memory of TBI mice by water maze test. This work provides a new perspective for the therapy of hypoxic brain injury.
研究领域:
神经科学
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药学
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材料科学
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生物医学工程
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产品关联
DOI
高影响因子
Frontiers in Aging Neuroscience
·
2019
·
IF 3.633
Wang Yu,Xia Jia,Shen Mengjun,Zhou Yifan,Wu Zhe,Shi Yuhuan,Xu Jianrong,Hou Lina,Zhang Rui,Qiu Zhuibai,Xie Qiong,Chen Hongzhuan,Zhang Yongfang,Wang Hao
Alzheimer’s disease (AD) is the main type of dementia and is characterized by progressive memory loss and a notable decrease in cholinergic neuron activity. As classic drugs currently used in the clinic, acetylcholinesterase inhibitors (AChEIs) restore acetylcholine levels and relieve the symptoms of AD, but are insufficient at delaying the onset of AD. Based on the multi-target-directed ligand (MTDL) strategy, bis-(-)-nor-meptazinol (BIS-MEP) was developed as a multi-target AChEI that mainly targets AChE catalysis and the β-amyloid (Aβ) aggregation process. In this study, we bilaterally injected Aβ oligomers and ibotenic acid (IBO) into the hippocampus of ICR mice and then subcutaneously injected mice with BIS-MEP to investigate its therapeutic effects and underlying mechanisms. According to the results from the Morris water maze test, BIS-MEP significantly improved the spatial learning and memory impairments in AD model mice. Compared with the vehicle control, the BIS-MEP treatment obviously inhibited the AChE activity in the mouse brain, consistent with the findings from the behavioral tests. The BIS-MEP treatment also significantly reduced the Aβ plaque area in both the hippocampus and cortex, suggesting that BIS-MEP represents a direct intervention for AD pathology. Additionally, the immunohistochemistry and ELISA results revealed that microglia (ionized calcium-binding adapter molecule 1, IBA1) and astrocyte (Glial fibrillary acidic protein, GFAP) activation and the secretion of relevant inflammatory factors (TNFα and IL-6) induced by Aβ were decreased by the BIS-MEP treatment. Furthermore, BIS-MEP showed more advantages than donepezil (an approved AChEI) as an Aβ intervention. Based on our findings, BIS-MEP improved spatial learning and memory deficits in AD mice by regulating acetylcholinesterase activity, Aβ deposition and the inflammatory response in the brain.
研究领域:
神经科学
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药理学
·
神经退行性疾病
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行为神经科学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）