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Neural Regeneration Research 2025年第1期20卷 203-204页

作者： Vishal Singh Arnab Choudhury Hyung Jin Ahn department of pharmacology Physiology and NeurosciencesRutgers-New Jersey Medical SchoolNewarkNJUSA Brain Health institute Rutgers UniversityPiscatawayNJUSA

Alzheimer’s disease(AD)stands out as the primary manifestation of age-related dementia,portraying a chronic neurodegenerative disorder distinguished by the accumulation of fibrillar amyloid-β(Aβ)plaques and neurofibrillary tangles of hyperphosphorylated ***,from a clinical standpoint,AD presents itself as a complex condition with a spectrum of dysfunctions rather than a singular pathological *** often-overlooked aspect of the disease is the presence of extensive cerebrovascular abnormalities,given that the majority of AD patients experience altered cerebral blood flow,damaged vasculature,increased microinfarcts and *** models of AD further support this observation,showing cerebrovascular dysfunction such as impaired cerebral blood flow and altered cerebrovascular reactivity(Tataryn et al.,2021;Gareau et al.,2023).

关键词： cerebrovascular dysfunction Alzheimer

Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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Neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso JoséMartínez-Hernández Alejandro Martín-Belmonte Rocío Alfaro-Ruiz Miriam Fernández Ana Esther Moreno-Martínez Mar Cuadrado-Tejedor Ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for Neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain Neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic ***,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

Altered thermal sensitivity in facial skin in chronic whiplash-associated disorders

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International Journal of Oral Science 2013年第3期5卷 150-154页

作者： Birgitta Hggman-Henrikson Ewa Lampa Erik Nordh department of Odontology Clinical Oral Physiology Umea University department of pharmacology and Clinical neurosciences Division of Clinical Neurophysiology Ume University

There is a close functional relationship between the jaw and neck regions and it has been suggested that trigeminal sensory impairment can follow whiplash *** of manageable routines for valid assessment of the facial sensory capacity is thus needed for comprehensive evaluations of patients exposed to such *** present study investigated facial thermal thresholds in patients with chronic whiplash-associated disorders（WADs）with both a qualitative method and quantitative sensory testing（QST）.Ten women with pain and dysfunction following a whiplash injury were compared to 10 healthy age-matched *** detection thresholds were assessed by qualitative chair-side testing and by QST according to the *** test sites in the facial skin（overlying each trigeminal branch bilaterally,and the midpoint of the chin）were *** detection warm and cold thresholds were defined as the mean values of 10 individual *** the WAD patients,the qualitative assessment demonstrated both reduced and increased sensitivity compared to the healthy,whereas QST systematically showed significantly higher detection thresholds（i.e.,decreased sensitivity）for both cold and warm *** the individuals who were assessed as having increased sensitivity in the qualitative assessment,the QST displayed either normal or higher thresholds,i.e.,decreased *** results suggest that QST is more sensitive for detecting thermal sensory disturbances in the face than a qualitative *** impaired thermal sensitivity among the patients corroborates the notion of altered thermal detection capacity induced by WAD-related pain.

关键词： jaw neck quantitative sensory testing thermal thresholds trigeminal whiplash injury

Synergistic facilitation of Bryostatin-1 and Vitamin E on classical conditioning of the rabbit （Oryctolagus cuniculus） nictitating membrane response

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Synergistic facilitation of Bryostatin-1 and Vitamin E on cl...

Amyotrophic lateral sclerosis: a complex syndrome that needs an integrated research approach

第十五届国际药理学大会

作者： Darwish Deya Schreurs Bernard G blanchette rockefeller neurosciences institute West Virginia University School of Medicine5700 HSS PO Box 9302Medical Center Drive Morgantown WV 26506 department of physiology and pharmacology and blanchette rockefeller neurosciences institute West Virginia University School of Medicine 5700 HSS PO Box 9302 Medical Center Drive Morgantown WV 26506

＜正＞ Our previous work has demonstrated that protein kinase C （PKC） is involved in classical conditioning. This study was to investigate if PKC modulator. Bryostatin - 1,was capable of facilitating rabbit conditioned NMR;and if there was a synergisticeffect between Bryostatin - 1 and Vitamin E. Bryostatin - 1 showed a dose - dependent increase in conditioned eyeblink responses from the fifth trace day. Compared to the paired rabbits receiving vehicle. Bryostatin - 1 alone, paired animals receiving both 10μg/kg Bryostatin - 1 and Vitamin E exhibited significantly more conditioned eyeblink responses. Bryostatin - 1 did not alter the reactivity to airpuff （US） and tone （CS）. These findings demonstrate a strong synergisticeffect on rabbit conditioned nictitating membrane responses between Bryostatin - 1 and Vitamin E and suggest Bryostatin - 1 and Vitamin E may be an optional treatment for learning disabilities and memory deficits in clinics.

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Neural Regeneration Research 2019年第2期14卷 193-196页

作者： Javier Riancho Francisco J.Gil-Bea Ana Santurtun Adolfo López de Munaín Service of Neurology Hospital Sierrallana-Idival CIBERNED (Center for Networked Biomedical Research on Neurodegenerative Diseases Ministry of Economy and Competitiveness Institute Carlos Ⅲ) neurosciences Area Institute Biodonostia department of physiology and pharmacology University of Cantabria-Idival department of Neurology University Hospital Donostia department of neurosciences University of the Basque Country Universidad País Vasco-Euskal Herria Unibertsitatea

Amyotrophic lateral sclerosis, the most common neurodegenerative disease affecting motor neurons, lacks an effective treatment. A small fraction of amyotrophic lateral sclerosis cases have a familial origin, related to mutations in causative genes, while the vast majority of amyotrophic lateral sclerosis cases are considered to be sporadic, resulting from the interaction between genes and environmental factors in predisposed individuals. During the past few years, dozens of drugs have been postulated as promising strategies for the disease after showing some beneficial effects in preclinical cellular and murine models. However, the translation into clinical practice has been largely unsuccessful and the compounds failed when were tested in clinical trials. This might be explained, at least partially, by the enormous complexity of the disease both from clinico-epidemiological and a pathogenic points of view. In this review, we will briefly comment on the complexity of the disease focusing on some recent findings, and we will suggest how amyotrophic lateral sclerosis research might be reoriented to foster the advance in the diagnostic and therapeutic questions.

关键词： amyotrophic lateral sclerosis ALS environment epidemiology genes phenotype therapy

阿尔茨海默病的药物治疗靶点及新药研发进展:我们还有新武器吗?

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中国药理学与毒理学杂志 2017年第7期31卷 701-706页

作者：胡薇薇侯雪芹廖儒佳张汉霆浙江大学医药学部浙江杭州310058 齐鲁医科大学(筹)药理学研究所山东泰安271016 departments of Behavioral Medicine & Psychiatry and physiology & pharmacology Blanchette Rockefeller Neurosciences InstituteWest Virginia University Health Sciences Center

阿尔茨海默病(AD)是一种慢性进行性神经系统变性疾病,为最常见的痴呆类型,其发病率逐年增加,目前已是继心血管疾病和肿瘤之后导致老年人死亡的第三大病因。由于AD的发病机制至今尚未完全明确,因此,抗AD相关药物研发进展缓慢,其前景不容... 详细信息

阿尔茨海默病(AD)是一种慢性进行性神经系统变性疾病,为最常见的痴呆类型,其发病率逐年增加,目前已是继心血管疾病和肿瘤之后导致老年人死亡的第三大病因。由于AD的发病机制至今尚未完全明确,因此,抗AD相关药物研发进展缓慢,其前景不容乐观。发展有效的抗AD药物成为当前AD研究领域的热点和难点。近日,由海内外众多神经精神药理研究领域的华人科学家组成的"神经精神科学微信群"就此进行了热烈的讨论。专家们指出,对AD主流病理假说的误导以及目前抗AD药物筛选平台的问题均可导致新药开发的误区。我们应从整体观、大数据的角度重新审视AD病理及治疗策略,寻找多靶点全方位的综合治疗手段,并可根据AD病理过程的更上游因素将病程分型。此外,AD患者脑内线粒体的损伤和功能障碍,长期暴露于低剂量电离辐射造成AD样的病理改变等,为AD的发病机制和防治策略提供新的视角和思路。

关键词：阿尔茨海默病靶点新药研发

Phosphodiesterases:novel targets for treatment of alcoholism

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中国药理学与毒理学杂志 2017年第5期31卷 454-455页

作者： LIU Xin WEN Rui-ting GONG Mei-fang XU Ying Nicolas GRAHAME XU Jiang-ping LIANG Jian-hui Marco CONTI 张汉霆 institute of pharmacology Taishan Medical University departments of Behavioral Medicine & Psychiatry and physiology & pharmacology Blanchette Rockefeller Neurosciences InstituteWest Virginia University Health Sciences Center department of Molecular and Cellular pharmacology School of Pharmaceutical SciencesPeking University department of pharmacology School of Pharmaceutical SciencesSouthern Medical University department of Pharmaceutical Sciences State University of New York at Buffalo department of Psychology Indiana University-Purdue University Indianapolis Center for Reproductive Sciences Department of ObstetricsGynecology and Reproductive SciencesUniversity of California 泰山医学院药理学研究所泰山医学院药学院美国西弗吉尼亚大学医学院中国旅美科技协会西弗吉尼亚分会美国西弗吉尼亚华人协会

OBJECTIVE Alcoholism is one of the most damaging psychiatric disorders and causes serious social and health problems in the world. However,there are no ideal treatments for this disease in ***(PDEs) are a superfamily of enzymes consisting of 11 PDE families that hydrolyze cyclicAMP(cA MP) and/or cyclicGMP(cGMP). Among them,PDE4 is critical in the control of intracellular cAMP levels and has been shown to play an important role in the regulation of ethanol ***,the functional role of PDE4 in mediating alcoholism remains unclear. METHODS Ethanol drinking and preference were examined using the two-bottle choice and/or drinking-in-dark(DID) test in high alcohol preferring(HAP) animals,including C57,HAP,and PDE4-subtype knockout mice,and Fawn-Hooded(FH/Wjd) rats,treated with or without the PDE4 inhibitor rolipram or roflumilast. Ethanol withdrawal-induced anxiety-and depressive-like behaviors were examined using the elevated plusmaze,holeboard,forced-swim,and tail-suspension tests in C57 mice or FH rats in the presence of PDE4 inhibition. Levels of cAMP,CREB were determined in brain regions. RESULTS Treatment with rolipram or roflumilast decreased ethanol intake and preference in two-bottle choice and DID tests in C57 and HAP mice as well as FH rats. Mice deficient in PDE4 B,but not PDE4 D,displayed similar effects to general PDE4 inhibition. In addition,rolipram reversed ethanol withdrawal-induced anxietyand depressive-like behaviors 1 d and 14 d,respectively,following withdrawal from ethanol drinking in the two-bottle choice in C57 mice or FH rats. Locomotor activity was not changed in either mice or rats treated with the PDE4 inhibitors. Levels of cAMP,p CREB in the brain were increased by *** The results provide solid evidence for the important role of PDE4 in ethanol consumptionand ethanol withdrawal-induced symptoms. Inhibitors of PDE4,in particular the PDE4 B isoform,can be a novel class of treatment for alcohol

关键词： phosphodiesterase alcohol drinking alcoholism anxiety depression rodents

Naringenin prevents experimental liver fibrosis by blocking TGFβ-Smad3 and JNK-Smad3 pathways

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World Journal of Gastroenterology 2017年第24期23卷 4354-4368页

作者： Erika Hernández-Aquino Natanael Zarco Sael Casas-Grajales Erika Ramos-Tovar Rosa E Flores-Beltrán Jonathan Arauz Mineko Shibayama Liliana Favari Víctor Tsutsumi José Segovia Pablo Muriel Laboratory of Experimental Hepatology Department of PharmacologyCinvestav-IPNApartado Postal 14-740Mexico City department of physiology Biophysics and NeurosciencesCinvestav-IPNApartado Postal 14-740Mexico City department of pharmacology School of MedicineAutonomous University of Baja CaliforniaMexicaliApartado Postal 21100 department of Infectomics and Molecular Pathogenesis Cinvestav-IPNApartado Postal 14-740Mexico City

AIM To study the molecular mechanisms involved in the hepatoprotective effects of naringenin(NAR)on carbon tetrachloride(CCl4)-induced liver *** Thirty-two male Wistar rats(120-150 g)were randomly divided into four groups:(1)a control group(n=8)that received 0.7%carboxy methyl-cellulose(NAR vehicle)1 m L/daily p.o.;(2)a CCl4 group(n=8)that received 400 mg of CCl4/kg body weight i.p.3 times a week for 8 wk;(3)a CCl4+NAR(n=8)group that received 400 mg of CCl4/kg body weight i.p.3times a week for 8 wk and 100 mg of NAR/kg body weight daily for 8 wk p.o.;and(4)an NAR group(n=8)that received 100 mg of NAR/kg body weight daily for 8 wk *** the experimental period,animals were sacrificed under ketamine and xylazine *** damage markers such as alanine aminotransferase(ALT),alkaline phosphatase(AP),γ-glutamyl transpeptidase(γ-GTP),reduced glutathione(GSH),glycogen content,lipid peroxidation(LPO)and collagen content were *** enzymatic activity of glutathione peroxidase(GPx)was *** histopathology was performed utilizing Masson’s trichrome and hematoxylin-eosin *** assays for MMP-9 and MMP-2 were carried *** TGF-β,α-SMA,CTGF,Col-I,MMP-13,NF-κB,IL-1,IL-10,Smad7,Smad3,p Smad3 and p JNK proteins were detected via western *** NAR administration prevented increases in ALT,AP,γ-GTP,and GPx enzymatic activity;depletion of GSH and glycogen;and increases in LPO and collagen produced by chronic CCl4 intoxication(P<0.05).Liver histopathology showed a decrease in collagen deposition when rats received NAR in addition to *** zymography assays showed that CCl4 produced an increase in MMP-9 and MMP-2gelatinase activity;interestingly,NAR administration was associated with normal MMP-9 and MMP-2 activity(P<0.05).The anti-inflammatory,antinecrotic and antifibrotic effects of NAR may be attributed to its ability to prevent NF-κB activation and the subsequent production of IL-1 and IL-10(P<0.05).NAR complet

关键词：纤维变性转变生长因素 -- Naringenin pSmad3 Smad3 JNK 原子因素 kappa 碳四氯化物

Alzheimer's Disease with the Comorbidity of Depression:A Unique Role of Phosphodiesterase-4(PDE4)-Mediated cAMP Signaling

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神经药理学报 2019年第Z1期 76-77页

作者： WANG Hao FU Hua-rong ZHANG Fang-fang CHEN Ying ZHOU Yan-meng XU Ying James M. O'Donnell ZHANG Han-ting institute of pharmacology Shandong First Medical University department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical SciencesUniversity at Buffalothe State University of New York departments of Behavioral Medicine & Psychiatry and physiology Pharmacology & Neurosciencethe Rockefeller Neurosciences InstituteWest Virginia University Health Sciences Center

Depression is highly correlated with Alzheimer’s disease(AD),but treatment for the comorbidity of both is lacking. Phosphodiesterase-4(PDE4),an enzyme that catalyzes the hydrolysis of cyclic AMP(cAMP),has been considered as a promising target for treatment of both memory loss in AD and depression. Using mouse models of AD,potent PDE4 inhibitors,and PDE4-subtype knockout mice,we demonstrated that PDE4,in particular the PDE4 D isoform,plays an important role in the comorbidity of memory loss and depression in AD. Treatment with the PDE4 inhibitor rolipram or roflumilast reversed memory deficits in novel object recognition and Morris water-maze tests in APP/PS1 double transgenic and 3 xTg-AD mice,which are widely used models for AD. Similarly,in the tail-suspension and forced-swimming tests,the PDE4 inhibitors reversed the decreased immobility in AD mice,suggesting antidepressant-like effects. The effects of PDE4 inhibitors were mimicked in the tests using mice deficient in PDE4 D,which displayed memory-enhancing and antidepressant-like effects,relative to the WT mice microinfused with beta-amyloid peptide 1-42 into the hippocampus. In addition,the PDE4 inhibitor treatment reversed the decreased ratio of Bcl-2/BAX and inhibited the increased expression of PDE4 D in the cerebral cortex and hippocampus of AD mice. Further,the PDE4 inhibitors reversed the decreased levels of cAMP and expression of phosphorylated cAMP response element-binding protein(CREB) and brain derived neurotrophic factor(BDNF) in AD mice. These were mimicked by PDE4 D deficiency and treatment with a PDE4 D relatively selective inhibitor. In conclusions,these results suggest that PDE4 is an important target for the comorbidity of memory loss and depression in AD,which appears to be mediated by PDE4 D-cAMP signaling.

关键词： Alzheimer’s disease PDE4 inhibitor cAMP signaling Alzheimer’s disease model memory depression

Zingiber officinale(Ginger)Methanol Extract Abates Kidney Dysfunction in Mice Co-exposed to Sub-chronic Alcohol Intoxication and Post-traumatic Stress Disorder

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Clinical Complementary Medicine and pharmacology 2023年第4期3卷 79-90页

作者： Olusegun G.Adebayo Benneth Ben-Azu Egwonor Akpofure Modo U.Emmanuel Iheanyichukwu Wopara Wadioni Aduema Lawrence Dayo Adedayo Jude Ijuo Abeje neurosciences and Oral physiology Unit Department of PhysiologyFaculty of Basic Medical SciencesCollege of MedicineUniversity of IbadanIbadan 200005Nigeria department of pharmacology Faculty of Basic Medical SciencesCollege of Health SciencesDelta State UniversityAbrakaDelta StateNigeria department of Medicine Evercare HospitalLekkiLagos State 105102Nigeria department of Biochemistry Faculty of Basic Medical SciencesPAMO University of Medical SciencesPort-HarcourtRiver State 500272Nigeria department of Biochemistry Faculty of SciencesRiver State UniversityPort HarcourtRiver State 500004Nigeria department of physiology Faculty of Basic Medical SciencesBayelsa Medical UniversityYenagoaBayelsa State 178Nigeria Neurophysiology Division Physiology ProgrammeCollege of Health ScienceBowen UniversityIwo 232101Nigeria

Background:Increasing number of people globally gives in to indiscriminate consumption of excess alcohol as a coping mechanism to relieve any form of physical or psychological ***,ethnomedicinal use of Zingiber officinale Roscoe(Ginger)have been shown to exhibit broad range of pharmacological benefits but no data has reported the phytotherapeutic treatment of Zingiber officinale methanol extract(MEZO)on alcohol-use disorder(AUD)and post-traumatic stress disorder(PTSD)-induced oxidative and inflammatory stress relevant to disruption of kidney functions in animal ***:To investigate the protective effect of MEZO on kidney-oxidative and inflammatory biomarkers in sub-chronic alcohol exacerbation of PTSD symptoms in ***:Male Swiss mice were administered 30%ethanol for two weeks and thereafter introduced to single pro-longed stress to induce AUD and PTSD respectively prior to post-treatment with MEZO and vitamin *** of oxidative stress,inflammatory cytokines,kidney functions,HPA-axis signaling molecules,vasodilator substance,and histopathology of the kidney were ***:Sub-chronic alcohol intoxication heightened PTSD-induced oxido-inflammatory stress,altered the kidney function indices and HPA-axis,and reduced nitric oxide production,which were ameliorated by the phytother-apeutic treatment with ***,severe degeneration and atrophy of renal tubules were ***,MEZO interventions strongly abated all these ***:Herein,the study shows that phytotherapeutic treatment with MEZO prevents the damaging effects of co-exposure to sub-chronic alcohol intoxication and PTSD.

关键词： Zingiber officinale Kidney Alcohol Single prolonged stress Oxidative stress