Catarina Gomes

Role of Microglia Adenosine A 2A Receptors in Retinal and Brain Neurodegenerative Diseases

Neuroinflammation mediated by microglial cells in the brain has been commonly associated with neurodegenerative diseases. Whether this microglia-mediated neuroinflammation is cause or consequence of neurodegeneration is still a matter of controversy. However, it is unequivocal that chronic neuroinflammation plays a role in disease progression and halting that process represents a potential therapeutic strategy. The neuromodulator adenosine emerges as a promising targeting candidate based on its ability to regulate microglial proliferation, chemotaxis, and reactivity through the activation of its G protein coupled A2A receptor (A2AR). This is in striking agreement with the ability of A2AR blockade to control several brain diseases. Retinal degenerative diseases have been also associated with microglia-mediated neuroinflammation, but the role of A2AR has been scarcely explored. This review aims to compare inflammatory features of Parkinsons and Alzheimers diseases with glaucoma and diabetic retinopathy, discussing the therapeutic potential of A2AR in these degenerative conditions.

Glial cell line-derived neurotrophic factor (GDNF) enhances dopamine release from striatal nerve endings in an adenosine A2A receptor-dependent manner

Both glial cell line-derived neurotrophic factor (GDNF) and adenosine influence dopaminergic function in the striatum. We now evaluated the GDNF effect on dopamine release from rat striatal nerve endings and if this effect of GDNF is modulated by adenosine A(2A) receptors. Dopamine release was evoked twice (S(1) and S(2)); GDNF was added before S(2) and drugs used to modify GDNF actions were present during both stimulation periods. The effect of GDNF was taken as the change in the S(2)/S(1) ratio in the absence and in the presence of GDNF in the same experimental conditions. GDNF (3-30 ng/ml) increased dopamine release from K(+) (20 mM, 2 min) stimulated synaptosomes and electrically (2 Hz, 2 min) stimulated striatal slices, an effect dependent upon tonic adenosine A(2A) receptor activation, since it was blocked by the A(2A) receptor antagonist, SCH 58261 (50 nM). Activation of A(2A) receptors with CGS 21680 (10 nM) potentiated the effect of GDNF in synaptosomes. CGS 21680 also potentiated the effect of GDNF in striatal slices, providing that GABAergic transmission was inhibited; if not, the action of GDNF was attenuated by CGS 21680. Blockade of GABAergic transmission per se increased dopamine release, but attenuated the effect of GDNF upon dopamine release in slices. The results suggest that GDNF enhances dopamine release by acting presynaptically at the striatum, an action that requires adenosine A(2A) receptor activity. Furthermore, in striatal slices, the action of GDNF as well as its modulation by adenosine A(2A) receptor activation appears to be also under control of GABAergic transmission.

GDNF control of the glutamatergic cortico-striatal pathway requires tonic activation of adenosine A2A Receptors

Glial cell line‐derived neurotrophic factor (GDNF) affords neuroprotection in Parkinson’s disease in accordance with its ability to bolster nigrostriatal innervation. We previously found that GDNF facilitates dopamine release in a manner dependent on adenosine A2A receptor activation. As motor dysfunction also involves modifications of striatal glutamatergic innervation, we now tested if GDNF and its receptor system, Ret (rearranged during transfection) and GDNF family receptor α1 controlled the cortico‐striatal glutamatergic pathway in an A2A receptor‐dependent manner. GDNF (10u2003ng/mL) enhanced (by ≈13%) glutamate release from rat striatal nerve endings, an effect potentiated (up to ≈30%) by the A2A receptor agonist CGS 21680 (10u2003nM) and prevented by the A2A receptor antagonist, SCH 58261 (50u2003nM). Triple immunocytochemical studies revealed that Ret and GDNF family receptor α1 were located in 50% of rat striatal glutamatergic terminals (immunopositive for vesicular glutamate transporters‐1/2), where they were found to be co‐located with A2A receptors. Activation of the glutamatergic system upon in vivo electrical stimulation of the rat cortico‐striatal input induced striatal Ret phosphorylation that was prevented by pre‐treatment with the A2A receptor antagonist, MSX‐3 (3u2003mg/kg). The results provide the first functional and morphological evidence that GDNF controls cortico‐striatal glutamatergic pathways in a manner largely dependent on the co‐activation of adenosine A2A receptors.

Blockade of Adenosine A2A Receptors Prevents Protein Phosphorylation in the Striatum Induced by Cortical Stimulation

Previous studies have shown that cortical stimulation selectively activates extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and immediate early gene expression in striatal GABAergic enkephalinergic neurons. In the present study, we demonstrate that blockade of adenosine A2A receptors with caffeine or a selective A2A receptor antagonist counteracts the striatal activation of cAMP–protein kinase A cascade (phosphorylation of the Ser845 residue of the glutamate receptor 1 subunit of the AMPA receptor) and mitogen-activated protein kinase (ERK1/2 phosphorylation) induced by the in vivo stimulation of corticostriatal afferents. The results indicate that A2A receptors strongly modulate the efficacy of glutamatergic synapses on striatal enkephalinergic neurons.

The mediating effect of work engagement on the relationship between self-leadership and individual innovation.

It has already been demonstrated that individual innovation within the workplace is the fundamental underpinning of high-performance organisations. The aim of this study is to explore the relationship between self-leadership, work engagement and individual innovation. Because innovation manifests itself when individuals feel engaged with their work, we propose that this positive affective motivational state will mediate the relationship between self-leadership skills and individual innovation. To study these relationships, data were collected from a sample of 337 nurses and doctors who work at an integrated health care unit. Our results show a positive relationship between self-leadership, work engagement and individual innovation. Furthermore, the results showed that work engagement had a mediating effect on the relationship between self-leadership and individual innovation. Overall, this research will contribute towards gaining more insights into the role that self-leadership and work engagement play in individual innovation. In addition, it will provide insights into new interventions that promote the development of innovation at work.

Promoting learning and innovation in organizations through complexity leadership theory

Purpose n n n n nCurrent organizations face a complex competitive landscape driven by globalization and technology that puts them in the course of a new economic age. This complexity stresses learning and innovation as fundamental mechanisms for organizational survival. This paper aims to propose that how learning and innovation emerge and affect organizational performance can be better understood through the complexity leadership theory. n n n n nDesign/methodology/approach n n n n nThe authors review literature on complexity leadership theory, learning and innovation in complex bureaucratic environments and then present reflections regarding how learning and innovation can be achieved through the interaction of three complexity leadership functions: adaptive, administrative and enabling. This conceptual framework suggests that individuals are in constant interaction, exchange information, influence each other and collectively produce emergent properties that promote effective learning and innovation. n n n n nFindings n n n n nWe propose that learning and innovation can be better achieved in organizations if the complexity leadership theory is applied as an alternative to centralized forms of influence and control. n n n n nOriginality/value n n n n nThis paper presents a reflection on the benefits of the complexity leadership theory as an alternative framework to understand organizational leadership. Furthermore, this paper proposes that the complexity leadership theory is more adequate to generate learning and innovation in complex, fast-changing work environments.

Training for happiness: the impacts of different positive exercises on hedonism and eudaemonia

Abstract Theoretical conceptions on happiness have generally considered two broad perspectives: hedonic enjoyment and eudaemonia. However, most research on how to improve people’s happiness has focused primarily on the enhancement of hedonic happiness. In this longitudinal experimental study we test the differential impact of two positive exercises—Best Possible Selves and the Lottery Question—on hedonic and eudaemonic happiness. The hypothesis that the practice of the Best Possible Selves exercise would increase hedonic happiness was confirmed. This effect was immediate and maintained a week after the exercise. Furthermore, this exercise also increased eudaemonic happiness. However, its effect decreased after a week. Contrary to what was expected the Lottery Question exercise decreased both eudaemonic happiness and hedonic happiness over time. We discuss implications of this study for the literature on positive psychological and behavioral interventions to increase happiness.

Leadership as an Emergent Feature in Social Organizations: Insights from A Laboratory Simulation Experiment.

Recent theoretical contributions have suggested a theory of leadership that is grounded in complexity theory, hence regarding leadership as a complex process (i.e., nonlinear; emergent). This article tests if complexity leadership theory promotes efficiency in work groups. 40 groups of five participants each had to complete four decision making tasks using the city simulation game SimCity4. Before engaging in the four decision making tasks, participants received information regarding what sort of leadership behaviors were more adequate to help them perform better. Results suggest that if complexity leadership theory is applied, groups can achieve higher efficiency over time, when compared with other groups where complexity leadership is not applied. This study goes beyond traditional views of leadership as a centralized form of control, and presents new evidence suggesting that leadership is a collective and emergent phenomenon, anchored in simple rules of behavior.

The Relation Between Family-Supportive Work Environment and Work–Family Conflict: Does Leader Support Act as a Moderator of This Relation in the Portuguese Navy?

This study tested the moderation effect that leader support had on the relation between a family-supportive work environment (FSWE) and work–family conflict (WFC) in the Portuguese Navy. Data were collected through the application of a questionnaire to 260 career Navy junior and senior officers. Results indicated that a positive relation existed between the FSWE and WFC, being so that more FSWE related to more WFC. When bringing leader’s support to the subject, the only relation found was between leader support and WFC in which less leader support related to more WFC. The results didn’t back up the hypothesis that leader support had a positive moderating impact on the relationship between an FSWE and WFC. Given this, the results are discussed considering the theory on WFC and possible implications for future research and practice are presented for the Portuguese Navy.