The open neuroscience journal最新文献

{"title":"Neuroprotective Role of Statins in Alzheimer`s Disease: Anti-Apoptotic Signaling~!2009-02-06~!2010-04-04~!2010-06-22~!","authors":"Waylon T. Hunt, Pradeep Salins, C. Anderson, F. Amara","doi":"10.2174/1874082001004010013","DOIUrl":"https://doi.org/10.2174/1874082001004010013","url":null,"abstract":"Alzheimer's disease (AD), a severe form of senile dementia is a neurodegenerative disorder. One of the most well characterized hallmarks of AD are extra-neuronal aggregates of amyloid-beta peptide (A� ), known as amyloid plaques. Recent epidemiological studies suggest a link between statin intake, and a lowered incidence of AD. Statins are 3-hydroxy-3-methylglutaryl co-enzyme reductase (HMG) inhibitors, which are one of the most commonly prescribed drug groups used to lower serum cholesterol levels in patients with heart disease. Some of the pleiotropic effects of statins which are gaining attention are its ability to reduce Aproduction and deposition, inhibit caspase-3 mediated apoptosis, and demonstrate anti-inflammatory properties by reducing interleukin-6 (IL-6) levels. The molecular mechanisms respon- sible for the pleiotropic effects of statins in promoting neuronal survival are not fully understood. Our own research has shown that statins promote anti-apoptotic responses against A� -neurotoxicity through � -catenin-TCF/LEF signaling how- ever, other anti-apoptotic statin mediated signaling pathways may also be involved. This review will describe AD patho- genesis, Aproduction, and the role of statins in mitigating these effects.","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"1 1","pages":"13-22"},"PeriodicalIF":0.0,"publicationDate":"2010-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83719093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell Calcium Extrusion Systems and their Role in Epileptogenesis~!2009-05-14~!2010-01-06~!2010-04-21~!","authors":"Jorge Bravo-Martínez, B. Delgado-Coello, J. Mas-Oliva","doi":"10.2174/1874082001004010001","DOIUrl":"https://doi.org/10.2174/1874082001004010001","url":null,"abstract":"The precise control for maintenance of a normal intracellular calcium concentration in eukaryote cells is ac- complished by several systems located at the plasma membrane, as well as several internal membrane systems. Neurons are especially sensitive to changes in these control systems, since when fail and calcium homeostasis disturbed, the cell's metabolism is immediately modified and a pathological condition emerges. Such a condition has been associated with epi- leptogenesis, and especially to those mechanisms associated to calcium entrance or ON mechanisms. On the other hand, calcium extrusion mechanisms or OFF mechanisms, have been investigated to a lesser extent and therefore remain much less understood. Here, we present a review of these calcium extrusion systems located at the plasma membrane considered to be critical in the process of epileptogenesis; first of all the plasma membrane calcium ATPase (PMCA) as the catalytic moiety of the enzyme that moves calcium outwards in an energy-dependent fashion, and the Na + /Ca 2+ exchanger (NCX) coupled to the (Na + /K + )-ATPase. Based on present knowledge considering the wide range of isoforms found for PMCA and NCX and their specific kinetic characteristics, a hypothesis for their participation on the OFF mechanisms related to the genesis of epilepsy is discussed. Epilepsy can be defined as a chronic illness of diverse etiology characterized by recurrent crises due to an excessive and synchronic burden of cerebral neurons, eventually asso- ciated with diverse clinical and paraclinical manifestations. Epilepsy is a common pathology; World Health Organiza- tion (WHO) statistics revealed in the year of 2001 a preva- lence of 8.2 per 1,000 individuals in developed countries and 10 per 1,000 in developing countries. During the same year, incidence in developed countries was 50 per 100,000 indi- viduals in the general population, and 100 per 100,000 in developing countries. The analysis we have performed in the present study is related to the 50% of these patients that pre- sent by diverse external causes an acquired epilepsy (1). One very important period of epilepsy comprises epileptogenesis, i.e., the period in which epilepsy is developed, which can be considered the period between the lesion and the appearance of clinical manifestations. Epileptogenesis includes all phe- nomena that induce normal cells to discharge abnormally, which when repeated in a continuous fashion, produce an epileptic focus. For these phenomena to be expressed in cells, a change is required in the majority of systems control- ling neuronal excitability and inhibitory processes. Such phenomena allow an exaggerated abnormal discharge of neurons provoking hyperexcitability in the long term. During the period of epileptogenesis, there also appear aberrant in- terconnections that promote neuronal synchronization with the consequent clinical manifestations (1).","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"33 1","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2010-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84364707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Purines and the Anti-Epileptic Actions of Ketogenic Diets.","authors":"Susan A Masino,&nbsp;Masahito Kawamura,&nbsp;David N Ruskin,&nbsp;Jeremy Gawryluk,&nbsp;Xuesong Chen,&nbsp;Jonathan D Geiger","doi":"10.2174/1874082001004010058","DOIUrl":"https://doi.org/10.2174/1874082001004010058","url":null,"abstract":"<p><p>Ketogenic diets are high in fat and low in carbohydrates and represent a well-established and effective treatment alternative to anti-epileptic drugs. Ketogenic diets are used for the management of a variety of difficult-to-treat or intractable seizure disorders, especially pediatric refractory epilepsy. However, it has been shown that this dietary therapy can reduce seizures in people of all ages, and ketogenic diets are being applied to other prevalent medical conditions such as diabetes. Although used effectively to treat epilepsy for nearly 90 years, the mechanism(s) by which ketogenic diets work to reduce seizures remain ill-understood. One mechanism receiving increased attention is based on findings that ketogenic diets increase the brain energy molecule ATP, and may also increase the levels and actions of the related endogenous inhibitory neuromodulator adenosine. ATP and adenosine have both been identified as important modulators of seizures; seizures increase the actions of these purines, these purines regulate epileptic activity in brain, adenosine receptor antagonists are pro-convulsant, and adenosinergic mechanisms have been implicated previously in the actions of approved anti-epileptic therapeutics. Here we will review recent literature and describe findings that shed light on mechanistic relationships between ketogenic diets and the purines ATP and adenosine. These emerging mechanisms hold great promise for the effective therapeutic management of epileptic seizures and other neurological conditions.</p>","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"4 1","pages":"58-63"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3207247/pdf/nihms-318795.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40137315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenosine dysfunction and adenosine kinase in epileptogenesis.","authors":"Detlev Boison","doi":"10.2174/1874082001004020093","DOIUrl":"https://doi.org/10.2174/1874082001004020093","url":null,"abstract":"<p><p>Traditionally, epilepsy has been considered to be a disorder of neuronal dysfunction. Based on this dogma, drug development efforts have largely focused on neurocentric model systems to screen for compounds that affect the function of neurons. Unfortunately, about 30% of all patients with epilepsy - or more than 20 million worldwide - are refractory to classical neurocentric pharmacotherapy. The failure of neurocentric pharmacotherapy in epilepsy requires radical rethinking and the search for novel therapeutic targets. Research from recent years suggests that epilepsy is a disorder of astrocyte dysfunction. Astrocytes are key regulators of the brain's own anticonvulsant adenosine. Thus, any dysfunction in astrocyte metabolism will drastically affect the brain's ability to control excitability via adenosinergic neuromodulation. This review will focus on the astrocyte-based enzyme adenosine kinase (ADK) as the key regulator of synaptic adenosine. Astrogliosis - a pathological hallmark of the epileptic brain - leads to overexpression of the adenosine-removing enzyme ADK and therefore to adenosine deficiency. Evidence from transgenic animals demonstrates that overexpression of ADK per se is sufficient to trigger seizures. Consequently, pharmacological inhibition of ADK is very effective in suppressing seizures that are refractory to classical antiepileptic drugs. The recent definition of ADK as rational target to predict and to prevent seizures in epilepsy has prompted the development of focal adenosine augmentation therapies (AATs) that have been designed to selectively reconstitute adenosinergic signalling within an area of astrogliosis-based adenosine-dysfunction. This therapeutic challenge has experimentally been met with polymeric or stem cell based brain implants to afford the focal delivery of adenosine.</p>","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"4 ","pages":"93-101"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1874082001004020093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29204793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microtubules in Dendritic Spine Development and Plasticity.","authors":"Jiaping Gu,&nbsp;James Q Zheng","doi":"10.2174/1874082000903020128","DOIUrl":"https://doi.org/10.2174/1874082000903020128","url":null,"abstract":"<p><p>Recent studies indicate that microtubules (MTs) may play an important role in spine development and dynamics. Several imaging studies have now documented the exploration of dendritic spines by dynamic MTs in an activity-dependent manner. Furthermore, it was found that alterations of MT dynamics by pharmacological and molecular approaches exert profound influence on the development and plasticity of spines associated with neuronal activity. It is reasonable to speculate that dynamic MTs may be responsible for targeted delivery of specific cargos to a selected number of spines and/or for interacting with the actin cytoskeleton to generate the structural changes of spines associated with synaptic modifications.</p>","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"3 ","pages":"128-133"},"PeriodicalIF":0.0,"publicationDate":"2009-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842989/pdf/nihms184701.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28872811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hot Topic: [Exciting Dendritic Spines]","authors":"Chi W. Pak, J. R. Bamburg","doi":"10.2174/1874082000903010052","DOIUrl":"https://doi.org/10.2174/1874082000903010052","url":null,"abstract":"","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"120 1","pages":"52-153"},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83952934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delayed Development of Dendritic Spines in Fxr2 Knockout Mouse","authors":"Jinbo Deng, A. Dunaevsky","doi":"10.2174/1874082000903010148","DOIUrl":"https://doi.org/10.2174/1874082000903010148","url":null,"abstract":"Fragile X syndrome, the most common form of inherited mental retardation is caused by silencing of the Fmr1 (fragile x mental retardation-1) gene. Two mammalian homologues of Fmr1 have been identified: fragile X-related Pro- tein 1 (Fxr1) and Protein 2Fxr2. Aberrations in dendritic spines of Fragile X syndrome patients and Fmr1 null mice im- plicate FMRP in synapse fo rmation and function. However, no structural analysis has been performed on Fxr2 null mice. Here we examined dendritic spines in brains of Fxr2 KO mouse. We report that at the age of 2 weeks, unlike in the Fmr1 null mice, spines in the somatosensory cortex and the hippocampus of Fxr2 null mice are less dense compared to wild type mice. On the other hand, there is an increase in spine length similar to that reported in the Fmr1 null mice. These dif- ferences in spine density and morphology are no longer detected by the age of 4 weeks. Our results indicate for the first time that Fxr2 plays a role in spine development and further suggest that Fxr2 has only partially overlapping function with Fmr1.","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"71 1","pages":"148-153"},"PeriodicalIF":0.0,"publicationDate":"2009-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84273368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct Roles of the Rho-GTPase Associated Kinases PAK and ROCK in the Regulation of Dendritic Spines and Synaptic Plasticity","authors":"S. Asrar, Zhengping Jia","doi":"10.2174/1874082000903010108","DOIUrl":"https://doi.org/10.2174/1874082000903010108","url":null,"abstract":"Dendritic spines are highly specialized neuronal structures that are the major postsynaptic sites for excitatory input. These actin-rich expansions are highly versatile in adapting their morphology and density towards the support of synaptic transmission and plasticity. Among the chief factors known to be crucial in the modulation of the actin cytoskele- ton, the Rho-GTPases and their associated signaling effectors are particularly important. This signaling system is involved in numerous regulatory processes, including cell morphology, structural dynamics and cell motility. Accordingly, the dis- ruption of Rho-related signaling has a profound effect on the integrity of neurons, resulting in abnormalities with neurite outgrowth, dendritic arborization, spine properties and plasticity. These perturbations can dramatically alter normal synap- tic function, including hippocampal long-term potentiation (LTP), resulting in cognitive defects. Additionally, Rho- GTPase-associated signaling disorders have also been implicated in numerous forms of mental retardation. Therefore, the elucidation of the underlying mechanisms involved in this pathway and their critical association with dendritic spines re- mains a major focus of research concerning the cellular basis of cognitive function. Here we will discuss our recent data obtained utilizing knockout animals deficient in the expression of PAKs (p21-activated kinases) and ROCKs (Rho- kinases), predominant protein kinases known to be directly activated by the Rho-GTPases. A downstream target for both PAKs and ROCKs, LIMKs (Lin-11, Isl-1, and Mec-3 kinase), will also be discussed. While it is evident that these kinase families all serve towards spine and synaptic regulation, their individual roles in the achievement of this goal may be quite different.","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"214 1","pages":"108-116"},"PeriodicalIF":0.0,"publicationDate":"2009-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76588491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spine Morphology and Plasticity in X-linked Mental Retardations","authors":"J. Arikkath","doi":"10.2174/1874082000903010134","DOIUrl":"https://doi.org/10.2174/1874082000903010134","url":null,"abstract":"In the past several years, a multitude of genes has been linked to mental retardations in humans, in particular the most commonly occurring X-linked mental retardations. An emerging idea is that structural and functional abnormali- ties in spines and synapses are a common feature of mental retardations. Consistent with this concept, a number of genes that control synaptic function have been implicated in X-linked mental retardations. In this review we discuss aberrations in spine and synapse structure and function in X-linked human mental retardations and corresponding mouse models with mutations in genes that modulate synaptic structure and function. A thorough understanding of these synaptic structures and abnormalities would enhance our knowledge of the normal process of learning and understand how synaptic aberra- tions contribute to cognitive deficits such as those observed in mental retardations.","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"23 1","pages":"134-147"},"PeriodicalIF":0.0,"publicationDate":"2009-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75409337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signaling Through Actin to Regulate Spine Formation and Function","authors":"H. Okada, S. Soderling","doi":"10.2174/1874082000903010097","DOIUrl":"https://doi.org/10.2174/1874082000903010097","url":null,"abstract":"Recent progress has greatly expanded our view of how signaling pathways regulate the actin cytoskeleton in post-synaptic spines. These studies reveal a complex interplay between pathways that highlight the role of the actin cy- toskeleton during the development of spines as well as in response to stimuli that modify synaptic strength. This review discusses the results from these studies that include biochemical, cellular, and genetic approaches to understanding excita- tory synapse formation and function.","PeriodicalId":88753,"journal":{"name":"The open neuroscience journal","volume":"41 1","pages":"97-107"},"PeriodicalIF":0.0,"publicationDate":"2009-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82249980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}