Extrasynaptic CaMKIIα is involved in the antidepressant effects of ketamine by downregulating GluN2B receptors in an LPS-induced depression model

2020 ◽  
Author(s):  
Xiao-Hui Tang ◽  
Guang-Fen Zhang ◽  
Ning Xu ◽  
Gui-Fang Duan ◽  
Min Jia ◽  
...  

Abstract Background A subanesthetic dose of ketamine provides rapid and effective antidepressant effects, but the molecular mechanism of this treatment remains elusive. Methods In this study, we investigated the role of CaMKIIα in the antidepressant effects of ketamine using an LPS-induced mouse model of depression, explored the different changes of CaMKIIα in the synaptic and extrasynaptic regions of the hippocampus, and clarified the relationship between CaMKIIα and GluN2B from extrasynaptic perspective. Results Ketamine (10 mg/kg, i.p.) administration attenuated the LPS-induced increase in extrasynaptic CaMKIIα activity (p-CaMKIIα) and extrasynaptic GluN2B localization and phosphorylation and that ketamine exerted antidepressant effects. Immunoprecipitation assay revealed that in the extrasynaptic region of the hippocampus, p-CaMKIIα bound to GluN2B, and ketamine administration attenuated the enhanced interaction between p-CaMKIIα and GluN2B induced by LPS. KN93, a CaMKIIα inhibitor, could also reverse the high level of extrasynaptic p-CaMKIIα, reduce hippocampal extrasynaptic GluN2B localization and phosphorylation, and exert antidepressant effects. Additional changes downstream of the ketamine-induced changes in extrasynaptic GluN2B included rescuing the downregulated expression of p-CREB, BDNF, and GluR1 and reversing the impaired induction of LTP in the hippocampus induced by LPS. Conclusion These results indicate that extrasynaptic CaMKIIα plays a key role in the cellular mechanism of ketamine's antidepressant effect and is related to the down-regulation of extrasynaptic GluN2B localization and phosphorylation and further affects synaptic plasticity.

2019 ◽  
Vol 20 (14) ◽  
pp. 3407 ◽  
Author(s):  
Paola Imbriani ◽  
Annalisa Tassone ◽  
Maria Meringolo ◽  
Giulia Ponterio ◽  
Graziella Madeo ◽  
...  

Caspases are a family of conserved cysteine proteases that play key roles in multiple cellular processes, including programmed cell death and inflammation. Recent evidence shows that caspases are also involved in crucial non-apoptotic functions, such as dendrite development, axon pruning, and synaptic plasticity mechanisms underlying learning and memory processes. The activated form of caspase-3, which is known to trigger widespread damage and degeneration, can also modulate synaptic function in the adult brain. Thus, in the present study, we tested the hypothesis that caspase-3 modulates synaptic plasticity at corticostriatal synapses in the phosphatase and tensin homolog (PTEN) induced kinase 1 (PINK1) mouse model of Parkinson’s disease (PD). Loss of PINK1 has been previously associated with an impairment of corticostriatal long-term depression (LTD), rescued by amphetamine-induced dopamine release. Here, we show that caspase-3 activity, measured after LTD induction, is significantly decreased in the PINK1 knockout model compared with wild-type mice. Accordingly, pretreatment of striatal slices with the caspase-3 activator α-(Trichloromethyl)-4-pyridineethanol (PETCM) rescues a physiological LTD in PINK1 knockout mice. Furthermore, the inhibition of caspase-3 prevents the amphetamine-induced rescue of LTD in the same model. Our data support a hormesis-based double role of caspase-3; when massively activated, it induces apoptosis, while at lower level of activation, it modulates physiological phenomena, like the expression of corticostriatal LTD. Exploring the non-apoptotic activation of caspase-3 may contribute to clarify the mechanisms involved in synaptic failure in PD, as well as in view of new potential pharmacological targets.


2015 ◽  
Vol 43 (5) ◽  
pp. 757-766 ◽  
Author(s):  
Yueran Wen ◽  
Liu Liu

Based on a survey of 147 Chinese employees, we examined the relationship between perceived career plateau and turnover intention, and the moderating role of career anchor in challenge in this process. We hypothesized that perceived career plateau would be positively related to turnover intention, and that this relationship would be stronger in employees with a higher level of career anchor in challenge than in those with a lower level. The results showed that perceived career plateau had a strong positive relationship with turnover intention, especially in employees with a high level of career anchor in challenge. These findings have implications for research in career development and turnover intention, as well as in management practices.


2018 ◽  
Vol 28 (6) ◽  
pp. 733-751 ◽  
Author(s):  
Keo Mony Sok ◽  
Phyra Sok ◽  
Lan Snell ◽  
Pingping Qiu

Purpose The purpose of this paper is to examine the role of frontline service employees (FSEs) motivation (enjoyment of work and driven to work) and ability (customer service ability) in the relationship between TFL and employee service performance. Design/methodology/approach This is a survey-based study which involves 534 FSEs and 135 supervisors in a hair salon setting. Hierarchical regression analysis was used to test the proposed hypotheses. Findings Results show that TFL is significantly related to employee service performance; this relationship is enhanced with the presence of driven to work; yet, it is neutralized with the presence of enjoyment of work. Further, the three-way interaction of TFL, enjoyment of work and customer service ability as well as TFL driven to work, and customer service ability are negatively associated with employee service performance. Practical implications The results advance service managers’ understanding of the importance of FSEs motivation and ability if they are to fully reap the benefits from their FSEs. The role of leader is not always effective in all situations. FSEs with high level of enjoyment of work and customer service ability would least rely on the guidance and support from the supervisors. Originality/value This research is one of the first to examine the role of subordinate’s characteristics (motivation – enjoyment of work and driven to work and ability – customer service ability) as the key moderators in the relationship between TFL and employee service performance.


Author(s):  
Kordiana K Rangga ◽  
Indah Listiana

<p align="center"><strong>ABSTRACT</strong></p><pre><em>                </em><em>Farmer groups are a forum for farmers to make it easier for farmers to carry out their farming, if the farmer group runs effectively in accordance with the goals of the group. Effective farmer groups cannot be separated from the role of group leaders. The head of the farmer group has an important role in supporting the group to achieve its group goals. Based on the background described, then </em><em>the purpose of this research are to know: the effectiveness of paddy farmer group; the leadership level of farmer group; and the relationship between leadership of farmer group leader with the effectiveness of farmer group in Sukoharjo Sub District of Pringsewu Regency. This research was conducted in Sukoharjo Sub District Pringsewu Regency, with 73 respondents of paddy farmer.  Data was collected by using survey method with descriptive analysis and using statistical non parametric test rank spearman correlation to test hypothesis.  The results showed that</em><em> paddy farmer group in </em><em>Sukoharjo Sub District had a high level of effectiveness, had a medium level of leadership of farmer group leader; and leadership of farmer group had significant relationship with farmer group effectiveness.  </em></pre><p> </p><p>Keyword:<em>  effectiveness, </em><em>farmer group</em><em>, leadership.</em></p><p align="center"><strong> </strong></p><p align="center"><strong>ABSTRACT</strong></p><p>Kelompok tani merupakan wadah bagi petani agar memudahkan petani dalam menajalankan usahataninya, jika kelompok tani berjalan secara efektif sesuai dengan tujuan kelompoknya. Kelompok tani yang efektif tidak terlepas dari peran ketua kelompok. Ketua kelompok tani memiliki peran yang penting dalam mendukung kelompok mencapai tujuan kelompoknya. Berdasarkan latar belakang yang telah diuraikan, maka tujuan dari penelitian ini yaitu untuk mengetahui: keefektifan kelompok tani padi sawah; tingkat kepemimpinan ketua kelompok tani; dan hubungan antara tingkat kepemimpinan ketua kelompok tani dengan keefektifan kelompok tani padi sawah di Kecamatan Sukoharjo Kabupaten Pringsewu.  Penelitian ini dilakukan di Kecamatan Sukoharjo Kabupaten Pringsewu, dengan 73 petani responden. Metode pengumpulan data menggunakan metode survey, dengan anilisis deskriptif dan menggunakan uji statistik korelasi <em>rank spearman </em>non parametrik untuk menguji hipotesis. Hasil penelitian menunjukkan kelompok tani padi sawah memiliki tingkat keefektifan yang tinggi, memiliki tingkat kepemimpinan ketua kelompok yang sedang, dan kepemimpinan ketua kelompok tani memiliki hubungan yang nyata dengan keefektifan kelompok tani.</p><p> </p>


2022 ◽  
Vol 14 ◽  
Author(s):  
Shuang Chen ◽  
Da Xu ◽  
Liu Fan ◽  
Zhi Fang ◽  
Xiufeng Wang ◽  
...  

Epilepsy is one of the most common neurological disorders characterized by recurrent seizures. The mechanism of epilepsy remains unclear and previous studies suggest that N-methyl-D-aspartate receptors (NMDARs) play an important role in abnormal discharges, nerve conduction, neuron injury and inflammation, thereby they may participate in epileptogenesis. NMDARs belong to a family of ionotropic glutamate receptors that play essential roles in excitatory neurotransmission and synaptic plasticity in the mammalian CNS. Despite numerous studies focusing on the role of NMDAR in epilepsy, the relationship appeared to be elusive. In this article, we reviewed the regulation of NMDAR and possible mechanisms of NMDAR in epilepsy and in respect of onset, development, and treatment, trying to provide more evidence for future studies.


Author(s):  
Dalal Hamid Al-Dhahri, Arwa Abdullah Al-Ghamdi, Mogeda El-Sa

This study aims at investigating the relationship between cognitive biases and decision making from a sample of gifted secondary students. It also aims at identifying the level of students’ cognitive biases and decision making and the differences in these two areas based on different classrooms. Random sampling was used to collect data from 139 female secondary students from the gifted group. Their age ranged between (16-18) with an average of (16.6), A descriptive method was adopted in the study. The research tools used consisted of DACOBS David Assessment of Cognitive biases Scale (Vander Gaag. et al., 2000), translated and standardized by the present researchers, and Tuistra’s decision making scale for teenagers (Tuinstra, et al., 2000). The findings of the study show a negative correlation between cognitive biases and decision making. Also, there were no differences between cognitive biases and decision making scores based on different classrooms. The study also shows a low level of students’ cognitive biases and a high level of decision making. The study recommends activating the role of mentors and students' counseling, planning for the values and behaviors that need to be acquired by students by including them in the annual goals of the school administration and participating in societal awareness and education.


Author(s):  
Huub J.M. Ruel

The relationship between Advanced Information Technologies (AIT) and organization is complex. Several theories and approaches try to get grip on this complex relationship. Adaptive Structuration Theory (AST) (DeSanctis and Poole, 1994) is one of them. It introduces the concept of spirit of AIT as an important determinant of AIT appropriation. AIT with a clear, coherent spirit will lead to a high level of AIT appropriation. But what about the role of the internal organizational environment? Does this constrain or support the role of the AIT’s spirit regarding AIT appropriation? This paper presents a study that aims to find an answer to this question. Three hypotheses were formulated and tested in four offices where employees used office technologies. Results confirm that a clear spirit is positively related to the level of appropriation as distinguished by DeSanctis and Poole (1994) and Poole and DeSanctis (1990). The results also make clear that this relationship is more positive among users who experienced a low level of change in the internal organizational environment along with the office technology implementation than among users who experienced a high level of change. Furthermore, the relationship is more positive among users with a low level of work autonomy than among users with a high level of work autonomy. This is not fully in line with our expectations. However, we think an explanation is available. We suppose that the answer lies in the office technology development process. All office technologies in this study’s offices were probably developed without anticipating the changes that office technology implementations might bring about in the internal organizational environment and with the aim to build systems that “reconfirm” the current “restrictive” work procedures. This study’s results once again indicate that office technology and other organizational components are interrelated.


2018 ◽  
Vol 19 (1) ◽  
pp. 60-75 ◽  
Author(s):  
Rómulo Díaz Díaz ◽  
Juan Manuel García Manso ◽  
Teresa Valverde Esteve ◽  
Enrique Arriaza Ardiles ◽  
Eduardo José Ramos Verde

The interactions of a Spanish football team of the Second A (10 official games) are analyzed, evaluating possible behavioral patterns that appear in a regular way in high level football. Observational methodology was used, by Polar Coordinates Analysis, to discover and evaluate the relationships generated between a considered focal behavior and the different conditioned categories, describing behavioral masses among the players. The matches were observed and recorded with an ad hoc observation instrument. The relations of dual character between the players taken as (focal behaviors) right midfielder and forward and the other players (conditioned conducts) were analyzed. The results show differences in the relationship established based on the outcome of the match. Matches that end with a favorable result, the right midfielder takes center stage, as a node of intermediation between the right centre back, left center back, left midfielder, and second striker. In these, the forward is clear receiver in the actions of completion. With the result of the unfavorable match, the connection networks change, generating a network of reciprocal interaction wider and different between the aforementioned player, right midfielder and the rest of the components, with special relation in the players that occupy the right back, left back, right centre back, right winger, left winger, second striker and forward. In these games the striker acquires a role of greater collaboration in the creation in offensive phases, participating as a node in the game network with intermediation functions. The interactions of a Spanish football team of the Second A (10 official games) are analyzed, evaluating possible behavioral patterns that appear in a regular way in high level football. Observational methodology was used, by Polar Coordinates Analysis, to discover and evaluate the relationships generated between a considered focal behavior and the different conditioned categories, describing behavioral masses among the players. The matches were observed and recorded with an ad hoc observation instrument. The relations of dual character between the players taken as (focal behaviors) right midfielder and forward and the other players (conditioned conducts) were analyzed. The results show differences in the relationship established based on the outcome of the match. Matches that end with a favorable result, the right midfielder takes center stage, as a node of intermediation between the right centre back, left center back, left midfielder, and second striker. In these, the forward is clear receiver in the actions of completion. With the result of the unfavorable match, the connection networks change, generating a network of reciprocal interaction wider and different between the aforementioned player, right midfielder and the rest of the components, with special relation in the players that occupy the right back, left back, right centre back, right winger, left winger, second striker and forward. In these games the striker acquires a role of greater collaboration in the creation in offensive phases, participating as a node in the game network with intermediation functions.


2020 ◽  
Vol 41 (8) ◽  
pp. 1287-1305
Author(s):  
Emre Burak Ekmekcioglu ◽  
Mahmure Yelda Erdogan ◽  
Alptekin Sokmen

PurposeThe purpose of this study is to test the moderating role of career-enhancing strategies (CESs) in the relationship between career commitment (CC) and subjective career success (CS).Design/methodology/approachData were collected from 217 full-time employees working for three different sectors in Ankara, Turkey. The participants were asked to respond to a self-reported survey. The hypotheses were tested using a hierarchical regression analysis.FindingsThe results indicated that CC had a significant and positive effect on subjective CS. Furthermore, the positive relationship between CC and subjective CS was stronger for employees with a high level of self-nomination and for employees with a high level of networking. However, creating career opportunities did not moderate the effects of CC on subjective CS.Research limitations/implicationsBecause this study had a cross-sectional research design, causality cannot be established among the study variables.Practical implicationsThe findings suggest a better understanding of the way CC is able to affect subjective CS through the networking and self-nomination CESs.Originality/valueThis study is original, in that no previous studies have investigated the moderating role of CESs in the relationship between CC and subjective CS.


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