RESUMO
Imbalances of iron and dopamine metabolism along with mitochondrial dysfunction have been linked to the pathogenesis of Parkinson's disease (PD). We have previously suggested a direct link between iron homeostasis and dopamine metabolism, as dopamine can increase cellular uptake of iron into macrophages thereby promoting oxidative stress responses. In this study, we investigated the interplay between iron, dopamine, and mitochondrial activity in neuroblastoma SH-SY5Y cells and human induced pluripotent stem cell (hiPSC)-derived dopaminergic neurons differentiated from a healthy control and a PD patient with a mutation in the α-synuclein (SNCA) gene. In SH-SY5Y cells, dopamine treatment resulted in increased expression of the transmembrane iron transporters transferrin receptor 1 (TFR1), ferroportin (FPN), and mitoferrin2 (MFRN2) and intracellular iron accumulation, suggesting that dopamine may promote iron uptake. Furthermore, dopamine supplementation led to reduced mitochondrial fitness including decreased mitochondrial respiration, increased cytochrome c control efficiency, reduced mtDNA copy number and citrate synthase activity, increased oxidative stress and impaired aconitase activity. In dopaminergic neurons derived from a healthy control individual, dopamine showed comparable effects as observed in SH-SY5Y cells. The hiPSC-derived PD neurons harboring an endogenous SNCA mutation demonstrated altered mitochondrial iron homeostasis, reduced mitochondrial capacity along with increased oxidative stress and alterations of tricarboxylic acid cycle linked metabolic pathways compared with control neurons. Importantly, dopamine treatment of PD neurons promoted a rescue effect by increasing mitochondrial respiration, activating antioxidant stress response, and normalizing altered metabolite levels linked to mitochondrial function. These observations provide evidence that dopamine affects iron homeostasis, intracellular stress responses and mitochondrial function in healthy cells, while dopamine supplementation can restore the disturbed regulatory network in PD cells.
Assuntos
Dopamina , Neurônios Dopaminérgicos , Homeostase , Ferro , Mitocôndrias , Doença de Parkinson , alfa-Sinucleína , Humanos , Ferro/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Homeostase/fisiologia , Homeostase/efeitos dos fármacos , Doença de Parkinson/metabolismo , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , alfa-Sinucleína/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Linhagem Celular Tumoral , Estresse Oxidativo/fisiologia , Estresse Oxidativo/efeitos dos fármacosRESUMO
Collective gatherings are often associated with the alignment of psychophysiological states between members of a crowd. While the process of emotional contagion has been studied extensively in dyads as well as at the population level, our understanding of its operation and dynamics as they unfold in real time in real-world group contexts remains limited. Employing a naturalistic design, we investigated emotional contagion in a public religious ritual by examining the relationship between interpersonal distance and autonomic arousal. We found that proximity in space was associated with heightened affective synchrony between participants in the context of the emotionally laden ritual (a Hindu procession) compared with an unstructured walk along the same route performed by the same group. Our findings contribute to the understanding of collective emotions and their underlying psychophysiological mechanisms, emphasizing the role of cultural practices in shaping collective emotional experiences.
RESUMO
BACKGROUND: The rugby league tackle has been identified as the game event with the greatest propensity for a clinically diagnosed concussion. This study aims to replicate the work conducted in professional rugby league and rugby union by examining Head Injury Assessment (HIA) events to determine the associated tackle characteristics that increase concussion risk in sub-elite rugby league players. This comparison between competition levels is important due to the less developed physiological and tackle proficiency characteristics of sub-elite rugby league players and the fewer resources available for an on-field diagnosis, compared to the elite level of the sport. RESULTS: Tackles resulting in Head Injury Assessments (HIAs, n = 131) and 2,088 tackles that did not result in a head injury were identified and coded from one season of the 2019 Queensland Cup. The body position of both ball carrier and tackler, tackle height, and body contact areas were evaluated. The propensity for tacklers to undergo a head injury assessment was 1.49 HIAs per 1,000 tackles, equating to a 2.5-fold higher risk than that of the ball carrier (0.59 HIAs per 1,000 tackles). The risk for an HIA was 2.75-fold greater when the tackler was upright (2.89 HIAs per 1,000 tackles) compared to a bent-at-the-waist tackler (1.05 HIAs per 1,000 tackles). The greatest risk for the tackler and ball carrier sustaining an HIA occurred when the tackle height was high, with head-to-head contact having the greatest propensity for an HIA (44.37 HIAs per 1,000 tackles). HIA risk was also greater for both players when the ball carrier did not employ an evasion strategy (3.73 HIAs per 1,000 tackles). CONCLUSIONS: The study replicates results from research in elite rugby league and rugby union. A combination of higher head contact/proximity and upright body position significantly increase an HIA risk. Tackler head position and ball carrier evasion behaviours also affect risk, suggesting that injury prevention strategies designed to reduce tackle height and improve tackle technique by focusing on head position, body position, and in a novel finding, ball carrier evasion, may reduce head injury risk in sub-elite rugby league players.