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Overexpression of Purinergic P2X4 Receptors in Hippocampus Rescues memory impairment in Rats with Type 2 Diabetes

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Neuroscience Bulletin 2020年第7期36卷 719-732页

作者： Ping-An Zhang Qian Sun Yong-Chang Li Rui-Xia Weng Rui Wu Hong-Hong Zhang Guang-Yin Xu Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience Soochow UniversitySuzhou 215123China Center for Translational Medicine The Affiliated Zhangjiagang Hospital of Soochow UniversitySuzhou 215600China The Second Affiliated Hospital of Soochow University Suzhou 215004China

Purinergic receptors have been reported to be involved in brain *** this study,we explored their roles and mechanisms underlying the memory impairment in rats with type 2 diabetes mellitus(T2 DM).T2 DM rats exhibited a worse performance in the T-maze and Morris water maze(MWM) than *** positive for P2 X purinoceptor 4(P2 X4 R) in the hippocampus were reduced and activated microglia were increased in T2 DM *** Amplicon PCR(LA-PCR) showed that DNA amplification of the p2 x4 r gene in the hippocampus was lower in T2 DM *** significantly reduced the number of activated microglia and the mean distance traveled by T2 DM rats in the *** importantly,P2 X4 R overexpression suppressed the activated microglia and rescued the memory impairment of T2 DM ***,T2 DM led to excessive activation of microglia in the hippocampus,partly through the DNA damagemediated downregulation of P2 X4 Rs,thus contributing to memory impairment.

关键词： Microglia P2X4 receptors DNA damage Type 2 diabetes mellitus memory impairment

TRPV4-induced Neurofilament Injury Contributes to memory impairment after High Intensity and Low Frequency Noise Exposures

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Biomedical and Environmental Sciences 2023年第1期36卷 50-59页

作者： YANG Yang WANG Ju QUAN Yu Lian YANG Chuan Yan CHEN Xue Zhu LEI Xue Jiao TAN Liang FENG Hua LI Fei CHEN Tu Nan Department of Neurosurgery and Key Laboratory of Neurotrauma Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Department of Neurosurgery The 904h Hospital of PLASchool of Medicine of Anhui Medical UniversityWuxi 214044JiangsuChina

Objective Exposure to high intensity, low frequency noise(HI-LFN) causes vibroacoustic disease(VAD),with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to *** Adult wild-type and transient receptor potential vanilloid subtype 4 knockout(TRPV4^(-/-)) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to *** The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilamentpositive nerve fibers in the cornu ammonis 1(CA1) and dentate gyrus(DG) hippocampal areas in wildtype mice. However, TRPV4^(-/-)mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN *** TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus,which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.

关键词： Low frequency noise memory impairment TRPV4 Neurofilament Nerve fibers HippocampusLow frequency noise memory impairment TRPV4 Neurofilament Nerve fibers Hippocampus

Antarctic krill peptides improve scopolamine-induced memory impairment in mice

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Food Bioscience 2022年第5期49卷 999-1009页

作者： Jingru Zheng Yuanhong Gao Jie Ding Na Sun Songyi Lin National Engineering Research Center of Seafood School of Food Science and TechnologyDalian Polytechnic UniversityDalian116034PR China Collaborative Innovation Center of Seafood Deep Processing Dalian Polytechnic UniversityDalian116034PR China

The study aims to investigate the repair effects of Ser-Ser-Asp-Ala-Phe-Phe-Pro-Phe-Arg(SSDAFFPFR)and Ser-Asn-Val-Phe-Asp-Met-Phe(SNVFDMF)peptides on scopolamine-caused memory impairment in *** experiments have revealed that Antarctic krill peptides can ameliorate scopolamine caused memory impairment by changing the behavior of *** comparison with the scopolamine group,the two peptides at a dose of 40 mg/kg could improve memory *** serum SOD activity(82.82±0.19 vs 79.47±2.42 U/mg prot)and hippocampal ACh level(101.46±3.23 vs 99.85±7.13μg/mg prot)of SSDAFFPFR were higher than those of *** AChE activity(0.20±0.03 vs 0.53±0.02 U/mg prot),hippocampal MDA level(1.56±0.01 vs 1.63±0.05 nmol/mg prot)and the serum MDA level(3.38±0.24 vs 3.88±0.21 nmol/mg prot)was lower than that of *** state of mouse hippocampal cells was further observed by a microscopic imaging *** addition,western blot analysis showed that SSDAFFPFR could significantly inhibit the expression of Bax,caspase-3,and p53,and promote the expression of BCL-XL,CREB,and BDNF,thus protecting hippocampal neurons in *** conclusion,the Antarctic krill peptide can repair scopolamine-induced memory impairment in mice.

关键词： Antarctic krill Bioactive peptide Hippocampus memory impairment Scopolamine mouse model Protein expression level

γ-secretase inhibitor DAPT prevents neuronal death and memory impairment in sepsis associated encephalopathy in septic rats

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Chinese Medical Journal 2014年第5期127卷 924-928页

作者： Huang Man Liu chunhui Hu Yueyu Wang Pengfei Ding Meiping Department of Intensive Care Unit Sir Run Run Shaw HospitalZhejiang University School of Medicine Hangzhou Zhejiang 310020 China

Background Brain dysfunction is a frequent complication of sepsis,usually defined as sepsis-associated encephalopathy （SAE）.Although the Notch signaling pathway has been proven to be involved in both ischemia and neuronal proliferation,its role in SAE is still ***,the effect of the Notch signaling pathway involved γ-secretase inhibitor DAPT on SAE in septic rats was investigated in a cecal ligation and puncture （CLP） *** Fifty-nine Sprague-Dawley rats were randomly divided into four groups,with the septic group receiving the CLP ***-four hours after CLP or sham treatment,rats were sacrificed and their hippocampus was harvested for Western blot ***-αexpression was determined using an enzyme-linked immunosorbent assay （ELISA） *** apoptosis was assessed by TUNEL staining,and neuronal cell death was detected by H＆E ***,a novel object recognition experiment was used to evaluate memory *** Our data showed that sepsis can increase the expression of hippocampal Notch receptor intracellular domain （NICD） and poly （adenosine diphosphate [ADP]-ribose） polymerase-1 （PARP-1）,as well as the inflammatory response,neuronal apoptosis,neuronal death,and memory dysfunction in *** γ-secretase inhibitor N-[N-（3,5-difluorophenacetyl）-1-alanyl]-S-phenylglycine t-butyl ester （DAPT） can significantly decrease the level of NICD and PARP-1,reduce hippocampal neuronal apoptosis and death,attenuate TNF-α release and rescue cognitive impairment caused by *** The neuroprotective effect of DAPT on neuronal death and memory impairment in septic rats,which could be a new therapeutic approach for treating SAE in the future.

关键词： DAPT γ-secretase memory impairment sepsis Notch

Effects of thioperamide on seizure development and memory impairment induced by pentylenetetrazole-kindling epilepsy in rats

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Chinese Medical Journal 2013年第1期126卷 95-100页

作者： ZHANG Li-san CHEN Jie-fang CHEN Guan-feng HU Xing-yue DING Mei-ping Department of Neurology Sir Run Run Shaw Hospital ZhejiangUniversity School of Medicine Hangzhou Zhejiang 310016China Key Laboratory of Medical Neurobiology of Chinese Ministry ofHealth Hangzhou Zhejiang 310058 China Department of Neurology Second Affiliated Hospital ZhejiangUniversity School of Medicine Hangzhou Zhejiang 310009China

Background Histamine H3 receptor antagonists have been considered as potential drugs to treat central nervous system diseases. However, whether these drugs can inhibit epileptogenesis remains unclear. This study aimed to investigate the effects of thioperamide, a selective and potent histamine H3 receptor antagonist, on the seizure development and memory impairment induced by pentylenetetrazole （PTZ）-kindling epilepsy in rats. Methods Chemical kindling was elicited by repeated intraperitoneal （ip） injections of a subconvulsant dose of PTZ （35 mg/kg） once every 48 hours for 12 times, and seizure activity of kindling was recorded for 30 minutes. Control rats were ip injected with saline instead of PTZ. Morris water maze was used to evaluate the spatial memory. Phosphorylated cyclic adenosine monophosphate response element binding protein （p-CREB） was tested by Western blotting in hippocampus. Results Intracerebroventricular （icv） injections with thioperamide （10 μg, 20 μg） 30 minutes before every PTZ injections, significantly prolonged the onset of PTZ-kindling and inhibited the seizure stages. PTZ-kindling seizures led to the impairment of spatial memory in rats, and thioperamide ameliorated the impairment of spatial learning and memory. Compared to non-kindling rats, there was a significant decrease in p-CREB level in hippocampus of the PTZ-kindling rats, which was reversed by thioperamide. Conclusions Thioperamide plays a protective role in seizure development and cognitive impairment of PTZ-induced kindling in rats. The protection of thioperamide in cognitive impairment is possibly associated with the enhancement of CREB-dependent transcription.

关键词： thioperamide seizure memory impairment pentylenetetrazole histamine

memory impairment occurred in mice deficient for lipoprotein lipase（LPL）is probably caused by decrease of pre-synaptic vesicles

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Memory impairment occurred in mice deficient for lipoprotein...

Garcinia Kola and Kolaviron Attenuates Bisphenol A-Induced memory impairment and Hippocampal Neuroinflammation in Male Wistar Rats

中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Colin ROSS Hayden MR George LIU Department of Medical Genetics University of British ColumbiaCentre for Molecular Medicine and TherapeuticsVancouverCanada Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education

＜正＞Lipid and associated proteins play an important role in causing Alzheimer’s disease（AD） and other forms of *** pre-clinical and clinical researches suggested that cholesterol-lowering medicines could meliorate the memory impairment in established *** lipase（LPL）,an essential molecule in lipoprotein metabolism in tissues such as adipose tissue has also been detected in the *** previous studies suggested the possible relationship between LPL mutation and dementia,how LPL in brain influences learning and memory is ***,we used behavior tests,immunohistocheniistry,western blotting,transmission electron microscopy（TEM） and other methods to investigate the mechanism（s） of this memory impairment,using the LPL-Knockout mouse *** first found that LPL-deficient mice had severe hippocampus-dependent memory impairment with behavior tests of radial arm water maze and step-down inhibitory *** interestingly,remarkable decrease of pre-synaptic vesicles as well as their marker synaptophysin was observed in the hippocampi from this kind of animals,but there was no significant neuron *** investigation established the animal model of memory impairment with LPL deficiency for the first *** the decrease of pre-synaptic vesicles caused by the imbalance of lipid homeostasis in brain might be the main reason of memory impairment in LPL-KO mice.

关键词： lipoprotein lipase(LPL) LPL deficiency hippocampus memory impairment pre-synaptic vesicles lipid

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Journal of Biosciences and Medicines 2024年第2期12卷 111-130页

作者： Nazizi Adamu Kayinu Bernard Omokheshi Adele Abayomi Oluwatosin Ige Applied and Environmental Physiology Unit Department of Physiology University of Ibadan Ibadan Nigeria Department of Physical and Health Education College of Education Akwanga Nigeria

Bisphenol A (BPA), a toxicant which can leach into food from plastic containers, is reported to induce neurotoxicity among others via oxidative mechanisms. However, antioxidant compounds have been suggested to mitigate BPA-induced toxicities. Garcinia kola (GK) and its bioactive compound, kolaviron, are well-established natural antioxidants, which can exert protective effects against BPA-induced toxicities. This study was designed to investigate the likely mitigating effect of GK and kolaviron on BPA-induced memory impairment and hippocampal neuroinflammation in male Wistar rats. Thirty-five rats were equally grouped and treated as follows: I and II received distilled water and corn oil, respectively at 0.2 mL, while III - VII received BPA (50 mg/kg), BPA + GK (200 mg/kg), BPA + kolaviron (200 mg/kg), GK and kolaviron, respectively for 28 days p.o. Thereafter, behavioral studies were done using the Novel Object Recognition and Y maze tests. Subsequently under anaesthesia, the hippocampus in each animal was dissected out, homogenized and analysed for malondialdehyde, superoxide dismutase, catalase, reduced glutathione, glutathione transferase, nitrites, interleukin-6, tumour necrosis factor-α, acetylcholinesterase, glutamate acid decarboxylase, and arginase activity. Data were analyzed by ANOVA and Tukey Post-hoc test at p p Garcinia kola and Kolaviron mitigate bisphenol A-induced memory impairment and neuroinflammation via antioxidant potentiation and neurotransmitter balance.

关键词： Bisphenol A memory impairment Neuroinflammation Neuroprotection Garcinia Kola Kolaviron Antioxidant

Anticonvulsant Effects of Chrysanthellum americanum L. (Vatke) Aqueous Extract in Mice Pilocarpine Model of Epilepsy and Associated memory impairment: Role of Antioxidant Defense System and Cholinergic Transmission

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Journal of Biosciences and Medicines 2023年第6期11卷 81-102页

作者： Yvette Nguezeye Fanta Sabine Adeline Yadang Simon Pale Vanessa Tita Jugha Hart Mann Alain Youbi Mambou Raymond Bess Bila Tambong Ako Ojongnkpot Germain Sotoing Taiwe Gabriel Agbor Agbor Elisabeth Ngo Bum Centre for Research on Medicinal Plants and Traditional Medicine Institute of Medical Research and Medicinal Plants Studies Yaoundé Cameroon Department of Biological Sciences Faculty of Science University of Ngaoundere Ngaoundéré Cameroon Department of Animal Biology and Conservation Faculty of Science University of Buea Buea Cameroon

Chrysanthellum americanum (L.) Vatke is a medicinal plant used by the traditional healers to treat epilepsy and associated memory impairment. This work aims at evaluating the anticonvulsant effects of Chrysanthellum americanum aqueous extract in mice pilocarpine model of epilepsy and associated memory loss. Mice were administered orally Chrysanthellum americanum aqueous extract (27.69, 69.22, 138.45, 276.9 mg/kg, prepared from the whole part) for test groups, intraperitoneally 300 mg/kg sodium valproate for the positive control group or orally 10 mL/kg distilled water for the negative control group, respectively, during a period of seven consecutive days. On the first day, temporal lobe epilepsy was induced by intraperitoneal injection of 360 mg/kg pilocarpine one hour after the administration of different treatment to mice, and the occurrence of status epilepticus was evaluated. On the second day, the anticonvulsant property was measured after the intraperitoneal injection of a sub-convulsive dose of picrotoxin (1 mg/kg). On the seventh day, the anti-amnesic properties of the extract were evaluated in the epileptic mice using the T-maze and open field paradigms. The results show that Chrysanthellum americanum extract significantly (p Chrysanthellum americanum (276.9 mg/kg) likewise sodium valproate (300 mg/kg) significantly (p Chrysanthellum americanum aqueous extract has anticonvulsant effects against pilocarpine induced-epileptic seizures and memory impairment. These properties could be mediated by the amelioration of antioxidant defense system and cholinergic neurotransmission in epileptic mice, which could partly justify the use of Chrysanthellum americanum in the traditional medicine for the treatment of epilepsy.

关键词： Chrysanthellum americanum Epilepsy memory impairment Oxidative Stress Cholinergic Transmission

The effects of antipsychotics on AKT/GSK3 signalling pathway:implications for treatment of memory impairment for schizophrenia

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The effects of antipsychotics on AKT/GSK3 signalling pathway...