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The effects of gonadal hormones on learning and memory in male mammals： A review

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Current Zoology 2011年第4期57卷 543-558页

作者： Stuart T. LEONARD Peter J. WINSAUER department of pharmacology and experimental Therapeutics Louisiana State University Health Sciences Center 1901 Perdido Street New Orleans LA 70112-1393

The primary role of the gonadal steroid hormones in mammals is to regulate reproduction and related behaviors; however, both androgens and estrogens are also integrally involved in mediating higher brain function and processes including cognition, neural development, and neural plasticity. In particular, a number of studies show that estradiol modulates dendritic spine growth and synapse density （synaptic plasticity） in the hippocampus of females, and that increased estradiol levels are generally associated with improvements on a variety of learning and memory tasks. While the majority of research has focused on the beneficial effects of estradiol in females, much less attention has been given to testosterone and its effects on learning and memory in males. Similar to estradiol titers in females, testosterone titers in males decline with age, albeit more gradually, and this decline has been correlated with impairment of certain cognitive tasks. Moreover, studies involving both humans and animals indicate that testosterone and its metabolites can augment responding on certain behavioral tasks, depending on the subject＇s current hormonal state, the response required, and the stimuli involved （e.g., those involving spatial or nonspatial stimuli）. While the exact mechanisms by which testosterone exerts its effects on learning and memory are not fully understood, recent findings suggest that testosterone modulates learning and memory in males through an interaction with the cholinergic system. The overall objective of this review is to discuss studies investigating the role of the gonadal hormones in mediating learning and memory processes in male mammals [Current Zoology 57 （4）： 543-558, 2011].

关键词： Testosterone Learning and memory Cholinergic system Mammals Cognition Androgens

Designing and generating a mouse model:frequently asked questions

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The Journal of Biomedical Research 2021年第2期35卷 76-90页

作者： Channabasavaiah BGurumurthy Thomas LSaunders Masato Ohtsuka department of pharmacology and experimental neuroscience Department of Pharmacology and Experimental NeuroscienceCollege of MedicineUniversity of Nebraska Medical CenterOmahaNE 68106-5915USA Mouse Genome Engineering Core Facility Department of Pharmacology and Experimental NeuroscienceCollege of MedicineUniversity of Nebraska Medical CenterOmahaNE 68106-5915USA department of Internal Medicine Division of Genetic MedicineUniversity of Michigan Medical SchoolAnn ArborMI 48109USA Transgenic Animal Model Core University of MichiganAnn ArborMI 48109USA department of Molecular Life Science Division of Basic Medical Science and Molecular MedicineTokai University School of MedicineIseharaKanagawa 259-1193Japan The Institute of Medical Sciences Tokai UniversityIseharaKanagawa 259-1193Japan

Genetically engineered mouse(GEM)models are commonly used in biomedical *** GEMs involve complex set of experimental procedures requiring sophisticated equipment and highly skilled technical *** of these reasons,most research institutes set up centralized core facilities where custom GEMs are created for research ***,on the other hand,when they begin thinking about generating GEMs for their research,several questions arise in their *** example,what type of model(s)would be best useful for my research,how do I design them,what are the latest technologies and tools available for developing my model(s),and finally how to breed GEMs in my *** there are several considerations and options in mouse designs,and as it is an expensive and time-consuming endeavor,careful planning upfront can ensure the highest chance of *** this article,we provide brief answers to several frequently asked questions that arise when researchers begin thinking about generating mouse model(s)for their work.

关键词： CRISPR transgenic mouse genetic engineering knockout mouse conditional knockout mouse knock-in mouse

Neuritogenic function of microglia in maternal immune activation and autism spectrum disorders

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Neural Regeneration Research 2021年第7期16卷 1436-1437页

作者： Srinidhi Venkatesan Kalavai Seiko Ikezu department of pharmacology&experimental Therapeutics Boston University School of MedicineBostonMAUSA

Autism spectrum disorder and maternal immune activation: Environmental factors during pregnancy, such as infections, maternal stress or autoimmune disorders, are closely associated with the prevalence of neurodevelopmental disorders including autism spectrum disorder(ASD), bipolar disorder and *** has been shown that severe infections during pregnancy cause maternal immune activation(MIA) and significantly increase the risk of ASD in the offspring although the mechanisms are poorly *** rodent MIA studies support this causal link by showing that offspring of dams administered with polyinosinic:polycytidylic acid(poly I:C), a viral mimetic Toll-like receptor 3 agonist, exhibit longlasting ASD-like behavioral abnormalities such as increased repetitive behavior, impaired social interaction and ***, MIA alters inflammatory cytokine expressions persisting through development and adulthood in the brain of the offspring, suggesting that chronic neuroimmune dysfunction plays a role in mediating the deleterious effects of MIA on neurodevelopment(Garay et al., 2013).

关键词： disorders impaired activation

Effects of extra-corporeal shock waves on penile hemodynamics and histopathology in rats

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Asian Journal of Andrology 2002年第4期4卷 249-253页

作者： Ahmet Tefekli Abdullah Armagan Bulent Erol Murat Celtik Isi Kilicaslan Asiye Nurten Ates Kadioglu department of Urology Department of UrologyDepartment of UrologyDepartment of UrologyDepartment of Pathology Medical Faculty of IstanbulDepartment of Neuroscience Experimental Research Institution University of lstanbul TurkeyDepartment of Urology

Aim: To study the effect of extra-corporeal shock wave (ESW) on the penile hemodynamics and histopathology in rats. Methods: Adult male Sprague-Dawley rats were divided at random into 3 groups. ESW application was performed with a Siemens Lithostar with the rats under anesthesia lying prone on the balloon probe. Rats in Group Ⅰ received a total of 1000 shocks at 18 kV and immediately underwent hemodynamic evaluation performed by direct electrostimulation of the cavernous nerve and measurement of intracavernous pressure (ICP). Rats in Group Ⅱ received 3 times 1000 shocks at 18 kV at weekly intervals and hemodynamic evaluation was performed 1 month after the last ESW application. Group Ⅲ served as the control. Histopathological examinations of penile tissues were done on Masson's trichrome and hematoxylin and eosin stained sections. Results: Penile hemodynamic evaluation showed a trend toward a diminished mean maximal ICP, duration of erection, ICP during the plateau phase and maximal ICP/blood pressure ratio in Group Ⅰ, although there was no significant significance. The mean latency period in Groups Ⅰ and Ⅱ was prolonged. Petechial bleeding within tunical layers and small loci of hemorrhage within the corpora cavernosa were observed in Group Ⅰ. However, histopathological examination failed to reveal any significant differences between the groups in terms of smooth muscle content, tunical thickness, organization of collagen bundles and elastic fiber-lattice framework. Conclusion: ESW has certain damaging effects on the penis. (Asian J Androl 2002 Dec; 4: 249-253)

关键词： penis extra-corporeal shock wave Peyronie's disease tunica albuginea

Ephrin-B2/EphA4 forward signaling is required for regulation of radial migration of cortical neurons in the mouse

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neuroscience Bulletin 2014年第3期30卷 425-432页

作者： Yan Hu Sen Li Hua Jiang Ming-Tao Li Jia-Wei Zhou department of pharmacology and Proteomics Center Zhongshan School of Medicine Sun Yat-Sen University Institute of neuroscience State Key Laboratory of Neuroscience Shanghai Institutes for Biological Sciences Chinese Academy of Sciences

Postmitotic neurons in the neocortex migrate to appropriate positions and form layered structures of nascent cortex during brain development. The migration of these neurons requires precise control and coordination of a large number of molecules such as axon guidance cues. The Eph-ephrin signaling pathway plays important roles in the development of the nervous system in a wide variety of ways, including cell segregation, axon pathfinding, and neuron migration. However, the role of ephrin-B2/ EphA4 signaling in cortical neuron migration remains elusive. Here we demonstrated that ephrin-B2 and its receptor EphA4 were expressed in complementary and overlapping patterns in the developing neocortex. Deletion of the EphA4 gene in the embryonic cerebral cortex resulted in faster migration of cortical neurons, whereas knockdown or overexpression of ephdn-B2 did not alter the normal process of migration. These results suggest that ephrin-B2 forward signaling through EphA4 is required for the precise control of cortical neuron migration.

关键词： neuron migration Eph receptor A4 ephrin-B2 cerebral cortex development

Interferon-gamma and neuropathy: balance between pain and neuroprotection

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Neural Regeneration Research 2022年第12期17卷 2700-2701页

作者： Valentina Ferrara Alessandra Toti Carla Ghelardini Lorenzo Di Cesare Mannelli department of neuroscience PsychologyDrug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology SectionUniversity of FlorenceFlorenceItaly

Chronic pain is sustained by a phenomenon of hyper-activation of nociceptive neurons both at peripheral(peripheral sensitization)and central(central sensitization)*** onset and maintenance of pain,however,is to be found in the interaction among the various cell populations in the nervous tissue including neurons and glia(Nam et al.,2016).The pathogenesis of neuropathic pain is extremely complex depending on the primary cause of nerve damage,*** nerve injury is associated with a robust inflammatory response while chemotherapy-induced pain is characterized by a modest phlogistic component(Di Cesare Mannelli et al.,2013).Despite these differences,a powerful common concept to explain the cellular mechanisms underlying pain is the activation of glia.

关键词： pain sustained

Emerging role of lysosomal calcium store as a hub of neuroprotection

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Neural Regeneration Research 2022年第6期17卷 1259-1260页

作者： Valentina Tedeschi Agnese Secondo Division of pharmacology Department of NeuroscienceReproductive and Odontostomatological SciencesSchool of Medicine“Federico II”University of NaplesNaplesItaly

Filled with more than 60 different types of hydrolases,the acidic organelle lysosome governs cellular digestion by removing damaged organelles and catabolic products(Xu and Ren,2015).Beyond the canonical role in the intracellular degradative pathways,lysosome precedes nutrient sensing,autophagy,immune cell signaling,metabolism and membrane repair.

关键词： metabolism removing store

Circadian dysrhythmia-linked diabetes mellitus: Examining melatonin's roles in prophylaxis and management

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World Journal of Diabetes 2018年第7期9卷 99-114页

作者： Adejoke Y Onaolapo Olakunle J Onaolapo Behavioural neuroscience/Neurobiology Unit Department of Anatomy Ladoke Akintola University of Technology Behavioural neuroscience/Neuropharmacology Unit Department of Pharmacology Ladoke Akintola University of Technology

Diabetes mellitus is a chronic, life-threatening metabolic disorder that occurs worldwide. Despite an increase in the knowledge of the risk factors that are associated with diabetes mellitus, its worldwide prevalence has continued to rise; thus, necessitating more research into its aetiology. Recent researches are beginning to link a dysregulation of the circadian rhythm to impairment of intermediary metabolism; with evidences that circadian rhythm dysfunction might play an important role in the aetiology, course or prognosis of some cases of diabetes mellitus. These evidences thereby suggest possible relationships between the circadian rhythm regulator melatonin, and diabetes mellitus. In this review, we discuss the roles of the circadian rhythm in the regulation of the metabolism of carbohydrates and other macronutrients; with emphasis on the importance of melatonin and the impacts of its deficiency on car-bohydrate homeostasis. Also, the possibility of using melatonin and its analogs for the "prophylaxis" or management of diabetes mellitus is also considered.

关键词： Chronobiology Dysmetabolism Insulin Pancreatic beta cell Melatonin receptors

Direct contacts of microglia on myelin sheath and Ranvier’s node in the corpus callosum in rats

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The Journal of Biomedical Research 2019年第3期33卷 192-200页

作者： Jingdong Zhang Xinglong Yang You Zhou Howard Fox Huangui Xiong department of pharmacology and experimental neuroscience University of Nebraska Medical Center department of Clinical and Scientific Training Affiliated Hospital to Academy of Military Medicine Sciences Center for Biotechnology University of Nebraska at Lincoln School of Veterinary Medicine and Biomedical Sciences

Over the recent years, it has been found that microglia pseudopodia contact synapses, detect sick ones and prune them, even in adult animals. Myelinated nerves also carry out plasticity in which microglia remove myelin debris by phagocytosis. However, it remains unknown whether microglia explore structures on nerve fibers, such as Ranvier’s node(RN) or myelin sheath, before they become debris. By double or triple staining RNs or myelin sheathes and microglia in healthy rat corpus callosum, this study unveiled direct contacts of microglia pseudopodia with RNs and with para-and inter-nodal myelin sheathes, which was then verified by electron microscopic observations. Our data indicated that microglia also explore unmyelinated nerve fibers. Furthermore, we used the animals with matured white matter;therefore, microglia may be actively involved in plasticity of matured white matter tracts as it does for synapse pruning, instead of only passively phagocytize myelin debris.

关键词： Ranvier’s node myelin sheath microglia contact matured white matter tract