The Effects of P75NTR on Learning Memory Mediated by Hippocampal Apoptosis and Synaptic Plasticity

2020 ◽  
Vol 26 ◽  
Author(s):  
Jun-Jie Tang ◽  
Shuang Feng ◽  
Xing-Dong Chen ◽  
Hua Huang ◽  
Min Mao ◽  
...  

: Neurological diseases bring great mental and physical torture to the patients, and have long-term and sustained negative effects on families and society. The attention to neurological diseases is increasing, and the improvement of the material level is accompanied by an increase in the demand for mental level. The p75 neurotrophin receptor (p75NTR) is a low-affinity neurotrophin receptor and involved in diverse and pleiotropic effects in the developmental and adult central nervous system (CNS). Since neurological diseases are usually accompanied by the regression of memory, the pathogenesis of p75NTR also activates and inhibits other signaling pathways, which has a serious impact on the learning and memory of patients. The results of studies shown that p75NTR is associated with LTP/LTD-induced synaptic enhancement and inhibition, suggest that p75NTR may be involved in the progression of synaptic plasticity. And its pro-apoptotic effect is associated with activation of proBDNF and inhibition of proNGF, and TrkA/p75NTR imbalance leads to pro-survival or pro-apoptotic phenomena. It can be inferred that p75NTR mediates apoptosis in the hippocampus and amygdale, which may affect learning and memory behavior. This article mainly discusses the relationship between p75NTR and learning memory and associated mechanisms, which may provide some new ideas for the treatment of neurological diseases.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Machhindra Garad ◽  
Elke Edelmann ◽  
Volkmar Leßmann

AbstractBDNF plays a crucial role in the regulation of synaptic plasticity. It is synthesized as a precursor (proBDNF) that can be proteolytically cleaved to mature BDNF (mBDNF). Previous studies revealed a bidirectional mode of BDNF actions, where long-term potentiation (LTP) was mediated by mBDNF through tropomyosin related kinase (Trk) B receptors whereas long-term depression (LTD) depended on proBDNF/p75 neurotrophin receptor (p75NTR) signaling. While most experimental evidence for this BDNF dependence of synaptic plasticity in the hippocampus was derived from Schaffer collateral (SC)-CA1 synapses, much less is known about the mechanisms of synaptic plasticity, in particular LTD, at hippocampal mossy fiber (MF) synapses onto CA3 neurons. Since proBDNF and mBDNF are expressed most abundantly at MF-CA3 synapses in the rodent brain and we had shown previously that MF-LTP depends on mBDNF/TrkB signaling, we now explored the role of proBDNF/p75NTR signaling in MF-LTD. Our results show that neither acute nor chronic inhibition of p75NTR signaling impairs MF-LTD, while short-term plasticity, in particular paired-pulse facilitation, at MF-CA3 synapses is affected by a lack of functional p75NTR signaling. Furthermore, MF-CA3 synapses showed normal LTD upon acute inhibition of TrkB receptor signaling. Nonetheless, acute inhibition of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of both intracellular and extracellular proBDNF cleavage, impaired MF-LTD. This seems to indicate that LTD at MF-CA3 synapses involves BDNF, however, MF-LTD does not depend on p75NTRs. Altogether, our experiments demonstrate that p75NTR signaling is not warranted for all glutamatergic synapses but rather needs to be checked separately for every synaptic connection.


Author(s):  
Oliver Bohl ◽  
Shakib Manouchehri

Firms have faced and explored the increased use of Web 2.0. Driven mainly by private users, Web 2.0 may also have significant implications for corporate actions and business models. By systematically scanning and verifying possible positive and negative effects on the value of their creation, firms might be able to formulate and establish well-grounded strategies for corporate Web 2.0 applications and services. To establish such a process in an effective and adequate manner, it is necessary to analyze the relationship between Web 2.0 and corporate added value. This chapter contributes to these efforts by demonstrating that the corporate use of Web 2.0 applications is reinforced by fundamental and long-term business trends. The discussion pertains to the possibilities emerging from the application of Web 2.0 paradigms to business models; the market model, the activity model, and the capital market model. The potentials, risks, mainsprings, and restrictions associated with the corporate use of Web 2.0 are evaluated.


2020 ◽  
Vol 6 (1) ◽  
pp. 103-111 ◽  
Author(s):  
Yosef Avchalumov ◽  
Chitra D. Mandyam

Alcohol is one of the oldest pharmacological agents used for its sedative/hypnotic effects, and alcohol abuse and alcohol use disorder (AUD) continues to be major public health issue. AUD is strongly indicated to be a brain disorder, and the molecular and cellular mechanism/s by which alcohol produces its effects in the brain are only now beginning to be understood. In the brain, synaptic plasticity or strengthening or weakening of synapses, can be enhanced or reduced by a variety of stimulation paradigms. Synaptic plasticity is thought to be responsible for important processes involved in the cellular mechanisms of learning and memory. Long-term potentiation (LTP) is a form of synaptic plasticity, and occurs via N-methyl-D-aspartate type glutamate receptor (NMDAR or GluN) dependent and independent mechanisms. In particular, NMDARs are a major target of alcohol, and are implicated in different types of learning and memory. Therefore, understanding the effect of alcohol on synaptic plasticity and transmission mediated by glutamatergic signaling is becoming important, and this will help us understand the significant contribution of the glutamatergic system in AUD. In the first part of this review, we will briefly discuss the mechanisms underlying long term synaptic plasticity in the dorsal striatum, neocortex and the hippocampus. In the second part we will discuss how alcohol (ethanol, EtOH) can modulate long term synaptic plasticity in these three brain regions, mainly from neurophysiological and electrophysiological studies. Taken together, understanding the mechanism(s) underlying alcohol induced changes in brain function may lead to the development of more effective therapeutic agents to reduce AUDs.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S895-S895
Author(s):  
Ayako Baba

Abstract OBJECTIVE: Long-term caregiver (child)/care-recipient (parent) relationships have both positive and negative effects on care. However, the mechanism of that impact is unclear. This study aimed to explore how parent–child relationships affect care and which aspects cause those effects. METHOD: Five hundred thirty-four adult children who were caring for or had cared for their parents at home completed the scales of parent–child psychological independence, the acceptance of care, care attitude, and care burden. Data were analyzed using a pass analysis with multiple group structural equation modeling to identify the relationship between parent–child psychological independence, acceptance of care, care attitude, and care burden, and the care dyad difference of the models. RESULT: 1) “Reliable relationship with parent” in parent–child psychological independence affected “resignation” and “understanding actively” in acceptance of care. 2) “Psychological individuation from the parent” in parent–child independence affected all subscales of care attitudes. 3) “Resistance” and “understanding actively” in acceptance of care and “auto-pilot” in care attitude affected care burden. 4) In mother–daughter caregiving, “resistance” and “resignation” had stronger effects on “auto-pilot” whereas “utilization of resource” and “flexible response” in care attitude and “resistance” had weaker effects on care burden. CONCLUSION: The relationship between long-term parent–child relationship and care were revealed. In some points, daughters who were caring for or had cared for their mothers had a different model from other care dyads. These results suggest that child caregivers should be supported mentally in accordance to their difficult points and dyads.


2016 ◽  
Vol 23 (3) ◽  
pp. 221-231 ◽  
Author(s):  
Victor Briz ◽  
Michel Baudry

Although calpain was proposed to participate in synaptic plasticity and learning and memory more than 30 years ago, the mechanisms underlying its activation and the roles of different substrates have remained elusive. Recent findings have provided evidence that the two major calpain isoforms in the brain, calpain-1 and calpain-2, play opposite functions in synaptic plasticity. In particular, while calpain-1 activation is the initial trigger for certain forms of synaptic plasticity, that is, long-term potentiation, calpain-2 activation restricts the extent of plasticity. Moreover, while calpain-1 rapidly cleaves regulatory and cytoskeletal proteins, calpain-2-mediated stimulation of local protein synthesis reestablishes protein homeostasis. These findings have important implications for our understanding of learning and memory and disorders associated with impairment in these processes.


2016 ◽  
Vol 27 (5) ◽  
pp. 481-490 ◽  
Author(s):  
Norimichi Itoh ◽  
Atsushi Enomoto ◽  
Taku Nagai ◽  
Masahide Takahashi ◽  
Kiyofumi Yamada

AbstractIt is well known that synaptic plasticity is the cellular mechanism underlying learning and memory. Activity-dependent synaptic changes in electrical properties and morphology, including synaptogenesis, lead to alterations of synaptic strength, which is associated with long-term potentiation (LTP). Brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling is involved in learning and memory formation by regulating synaptic plasticity. The phosphatidylinositol 3-kinase (PI3-K)/Akt pathway is one of the key signaling cascades downstream BDNF/TrkB and is believed to modulate N-methyl-d-aspartate (NMDA) receptor-mediated synaptic plasticity. However, the molecular mechanism underlying the connection between these two key players in synaptic plasticity remains largely unknown. Girders of actin filament (Girdin), an Akt substrate that directly binds to actin filaments, has been shown to play a role in neuronal migration and neuronal development. Recently, we identified Girdin as a key molecule involved in regulating long-term memory. It was demonstrated that phosphorylation of Girdin by Akt contributed to the maintenance of LTP by linking the BDNF/TrkB signaling pathway with NMDA receptor activity. These findings indicate that Girdin plays a pivotal role in a variety of processes in the CNS. Here, we review recent advances in our understanding about the roles of Girdin in the CNS and focus particularly on neuronal migration and memory.


2016 ◽  
Vol 16 (4) ◽  
pp. 669-696 ◽  
Author(s):  
Diana Escandón-Barbosa ◽  
Miguel Hernandez-Espallardo ◽  
Augusto Rodriguez

The literature in the field of internationalization has managed to link other areas of knowledge such as marketing to give an explanation to the establishment of strategies to survive in international markets. In this sense, the concept of international market orientation emerges that manages to explain how businesses design a strategy to improve the satisfaction of customer needs in international contexts. The purpose of this article is finding the factors that influence the relationship between the international market orientation and international results. In turn, the directors of export SME´s should be aware that entering international markets prematurely and achieving a significant percentage by volume of international sales does not necessarily guarantee better international performance. They should search for other types of resources or capabilities that permit better possibilities of obtaining competitive advantage in the long-term, such as the adoption of an international market orientation, which makes it possible to evaluate and analyze the internal and external factors present in a company’s internal dynamics. To achieve this objective is taken as the unit of analysis Colombian exporters companies through a sample of 319 surveys and that are processed in a hierarchical regression analysis. The main findings confirm that adopt a strategy of international orientation relative to other strategies such as innovative and entrepreneurial orientation does have positive effects on the internationalization of companies. However, this strategy has a tendency to saturation and therefore can generate negative effects on the international results.


2021 ◽  
Vol 162 (3) ◽  
pp. 83-90
Author(s):  
Árpád Farkas ◽  
Gábor Tomisa ◽  
Erika Kis ◽  
Alpár Horváth

Összefoglaló. A dohányzás káros hatásainak vizsgálata hosszú ideje az orvostudomány egyik legintenzívebben kutatott területe. A nagy tudományos érdeklődésnek köszönhetően ma már meggyőző evidenciák állnak rendelkezésre a hagyományos cigaretta használatának számos negatív hatásáról. Ezzel ellentétben a sokkal később bevezetett helyettesítő termékek veszélyeiről lényegesen kevesebbet tudunk. E körbe tartozik a manapság egyre népszerűbb elektromos cigaretta is, amelyre egyre több, egészségügyi kockázatot felmérő munka fókuszál. Ugyanakkor a több évszázados múltra visszatekintő és a világ bizonyos helyein sokáig népszerű vízipipa érdekes esetnek számít, mivel használóinak száma a nyugati világban az utóbbi időben megugrott, de az emberre gyakorolt hatása számos ponton még vita tárgyát képezi. A jelen munka célja, hogy a hazai és a nemzetközi szakirodalom alapján feltérképezze a hagyományos cigaretta, az elektromos cigaretta és a vízipipa fontosabb egészségügyi hatásait, és rámutasson azokra a kapcsolódó területekre, ahol további kutatások szükségesek. A szakirodalmi áttekintés során a különböző publikációs adatbázisokban fellelhető tudományos cikkeket elemeztük. A megvizsgált szakirodalom alapján a tartós dohányzásnak bizonyítottan a szív-ér rendszert és a légzőrendszert károsító hatása van, de növekvő számú bizonyíték utal a neurológiai káros hatásokra és a gasztroenterológiai hatásokra is. Ugyanakkor az elektromos cigaretta és a vízipipa esetében a bizonyított akut hatások mellett a hosszú távú hatásokat illetően további intenzív kutatásokra van szükség. Az elektromos cigaretta és a vízipipa esetében a hosszú távú hatások kapcsán a meggyőző evidencia hiánya semmiképpen nem jelenti azt, hogy ezen termékeket kockázatmentesnek kellene tekinteni, sőt a pulmonológusoknak és a döntéshozóknak mindent meg kell tenniük annak érdekében, hogy valamennyi dohánytermék törvényi szabályozása azok használatának visszaszorítását célozza. A kérdés fontosságának a COVID–19-pandémia különös aktualitást ad. Orv Hetil. 2021; 162(3): 83–90. Summary. Revealing the health effects associated with smoking has been in the focus of intense research for decades. Due to these research efforts, there is a convincing evidence regarding the negative effects of conventional cigarettes. However, much less is known about the replacement products such as electronic cigarettes. Moreover, the effects of waterpipes are also not fully explored, in spite of their long history. The scope of the present work is to survey the open literature to map the knowledge related to the health effects of conventional cigarettes, e-cigarettes and waterpipes. The analysis of the related scientific literature was performed based on papers retrieved in large publication repositories. Based on the reviewed literature, long-term smoking has demonstrated adverse effects on the respiratory as well as the heart and circulatory systems. In addition, the correlation between cigarette smoking and some gastroenterological and neurological diseases is also increasingly evident. By the same token, though the acute effects of e-cigarette and waterpipe are well documented, the protracted effects are still to be explored. The lack of pertinent information regarding the late effects of e-cigarette and hookah does not imply that there is no health risk associated with their consumption. On the contrary, in addition to the regular antismoke measures, pulmonologists and policy makers should do everything to lower the consumption of these alternative products. Orv Hetil. 2021; 162(3): 83–90.


2021 ◽  
Vol 15 ◽  
Author(s):  
Eve Honoré ◽  
Abdessattar Khlaifia ◽  
Anthony Bosson ◽  
Jean-Claude Lacaille

A distinctive feature of the hippocampal structure is the diversity of inhibitory interneurons. These complex inhibitory interconnections largely contribute to the tight modulation of hippocampal circuitry, as well as to the formation and coordination of neuronal assemblies underlying learning and memory. Inhibitory interneurons provide more than a simple transitory inhibition of hippocampal principal cells (PCs). The synaptic plasticity of inhibitory neurons provides long-lasting changes in the hippocampal network and is a key component of memory formation. The dendrite targeting interneurons expressing the peptide somatostatin (SOM) are particularly interesting in this regard because they display unique long-lasting synaptic changes leading to metaplastic regulation of hippocampal networks. In this article, we examine the actions of the neuropeptide SOM on hippocampal cells, synaptic plasticity, learning, and memory. We address the different subtypes of hippocampal SOM interneurons. We describe the long-term synaptic plasticity that takes place at the excitatory synapses of SOM interneurons, its singular induction and expression mechanisms, as well as the consequences of these changes on the hippocampal network, learning, and memory. We also review evidence that astrocytes provide cell-specific dynamic regulation of inhibition of PC dendrites by SOM interneurons. Finally, we cover how, in mouse models of Alzheimer’s disease (AD), dysfunction of plasticity of SOM interneuron excitatory synapses may also contribute to cognitive impairments in brain disorders.


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