Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures

Hippocampal neurogenesis is changed by brain injury. When neuroinflammation accompanies injury, activation of resident microglial cells promotes the release of inflammatory cytokines and reactive oxygen/nitrogen species like nitric oxide (NO). In these conditions, NO promotes proliferation of neural stem cells (NSC) in the hippocampus. However, little is known about the role of NO in the survival and differentiation of newborn cells in the injured dentate gyrus. Here we investigated the role of NO following seizures in the regulation of proliferation, migration, differentiation, and survival of NSC in the hippocampus using the kainic acid (KA) induced seizuremouse model. We show that NO increased the proliferation of NSC and the number of neuroblasts following seizures but was detrimental to the survival of newborn neurons. NO was also required for the maintenance of long-term neuroinflammation. Taken together, our data show that NO positively contributes to the initial stages of neurogenesis following seizures but compromises survival of newborn neurons.Foundation for Science and Technology (FCT, Portugal); COMPETE; FEDER [PTDC/SAU-NEU/102612/2008, PTDC/NEU-OSD/0473/2012, PEst-C/SAU/LA0001/2013-2014, PEst-OE/EQB/LA0023/2013-2014]; FCT, Portugal [SFRH/BPD/78901/2011, SFRH/BD/77903/2011

Regulation of injury-induced neurogenesis by Nitric Oxide

The finding that neural stem cells (NSCs) are able to divide, migrate, and differentiate into several cellular types in the adult brain raised a new hope for restorative neurology. Nitric oxide (NO), a pleiotropic signaling molecule in the central nervous system (CNS), has been described to be able to modulate neurogenesis, acting as a pro-or antineurogenic agent. Some authors suggest that NO is a physiological inhibitor of neurogenesis, while others described NO to favor neurogenesis, particularly under inflammatory conditions. Thus, targeting the NO system may be a powerful strategy to control the formation of new neurons. However, the exact mechanisms by which NO regulates neural proliferation and differentiation are not yet completely clarified. In this paper we will discuss the potential interest of the modulation of the NO system for the treatment of neurodegenerative diseases or other pathological conditions that may affect the CNS.Foundation for Science and Technology, (FCT, Portugal); COMPETE

Enablers, barriers, needs and preferences of physical activity in patients with COPD: does pulmonary rehabilitation play a role?

Low physical activity (PA) is associated with reduced survival in patients with chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation (PR) is essential in COPD management but its influence on patients’ perspectives about PA has been overlooked. This study assessed PA enablers, barriers, needs and preferences of patients attending or not PR. Two focus groups were conducted. One with 6 patients (70.2±8.8yrs; FEV1 55.5±14.4pp) attending a PR programme and another with 6 patients (65±7.6yrs; FEV1 58.2±21.4pp) naïve to PR. Interviews were analysed thematically. Enablers, barriers and needs were similar in both groups. Enablers/barriers fitted in health-related, psychosocial and environmental sub-themes. Identified enablers included: recognising that PA delays the onset of frailty and promotes wellbeing and functionality, being motivated by their family and health professionals, and the availability of green spaces. Main barriers were dyspnoea/fatigue and cough, exacerbations, comorbidities, fear of feeling breathless, frailty, cold/humid weather, smoke, crowded places and not having a current job. Main needs were health professional guidance and self-management education, including training on how to dose PA. Both groups identified (dog) walking as a preferred activity. Other PA preferences differed between groups: patients naïve to PR preferred activities such as playing with grandchildren, gardening and walking in daily tasks (e.g., shopping), whereas the PR group preferred exercise-related activities such as cycling or treadmill. This study provides guidance for future PA-enhancing interventions in those with/without PR previous experience.publishe

Test-retest reliability, agreement and construct validity of the International Physical Activity Questionnaire short-form (IPAQ-sf) in people with COPD

Artigo 107027. In Press, Journal Pre-proof. YRMED 107087. PII S0954-6111(22)00352-3.Introduction This study assessed the test-retest reliability/agreement and construct validity of the International Physical Activity Questionnaire short-form (IPAQ-sf) in patients with chronic obstructive pulmonary disease (COPD). It also explored differences in its validity according to age, sex and GOLD airflow obstruction levels. Methods 62 participants (68 ± 8 years, 53 males, FEV1 51 ± 23%pred) completed the Portuguese IPAQ-sf, wore an accelerometer for 7 days and completed a second IPAQ-sf. Test-retest reliability/agreement was assessed with Intraclass Correlation Coefficient (ICC2,1), 95% Limits of Agreement (LoA), standard error of measurement (SEM) and minimal detectable change (MDC95) for continuous variables, and percentage of agreement (%agreement) for categories (“active”/“inactive”). Validity was assessed with 95% LoA and Spearman's correlations (ρ) between IPAQ-sf 2 (METs-min/week, time in vigorous [VPA], moderate PA [MPA] and walking) and accelerometry (time in MVPA, VPA, MPA and step counts) for continuous variables; %agreement, Cohen's kappa, and sensitivity specificity and±predictive values for categories. Correlations were also performed for age, sex and GOLD airflow obstruction grades. Results Reliability was good (ICC2,1 = 0.707) with wide LoA (-6446—6409 METs-min/week). SEM and MDC95 were 1840 and 4971 METs-min/week, respectively. %agreement between the two IPAQ-sf was 84% (kappa = 0.660). Positive, moderate and significant correlations were found between IPAQ-sf and accelerometry (0.396 ≤ ρ ≤ 0.527, p  0.05). The strongest correlations were found in age (<65 years) and male (0.466 ≤ ρ ≤ 0.653, p < 0.05). %agreement between tools was 65% (kappa = 0.313), with high sensitivity (0.830) but low specificity (0.500). Conclusions The IPAQ-sf seems valid to be used in COPD but caution on its widespread use is recommended as its accuracy may be limited.info:eu-repo/semantics/publishedVersio

Differential contribution of the guanylyl cyclase-cyclic GMP-protein kinase g pathway to the proliferation of neural stem cells stimulated by nitric oxide

Nitric oxide (NO) is an important inflammatory mediator involved in the initial boost in the proliferation of neural stem cells following brain injury. However, the mechanisms underlying the proliferative effect of NO are still unclear. The aim of this work was to investigate whether cyclic GMP (cGMP) and the cGMP-dependent kinase (PKG) are involved in the proliferative effect triggered by NO in neural stem cells. For this purpose, cultures of neural stem cells isolated from the mouse subventricular zone (SVZ) were used. We observed that long-term exposure to the NO donor (24 h), NOC-18, increased the proliferation of SVZ cells in a cGMP-dependent manner, since the guanylate cyclase inhibitor, ODQ, prevented cell proliferation. Similarly to NOC-18, the cGMP analogue, 8-Br-cGMP, also increased cell proliferation. Interestingly, shorter exposures to NO (6 h) increased cell proliferation in a cGMP-independent manner via the ERK/MAP kinase pathway. The selective inhibitor of PKG, KT5823, prevented the proliferative effect induced by NO at 24 h but not at 6 h. In conclusion, the proliferative effect of NO is initially mediated by the ERK/MAPK pathway, and at later stages by the GC/cGMP/PKG pathway. Thus, our work shows that NO induces neural stem cell proliferation by targeting these two pathways in a biphasic manner. Copyright (C) 2012 S. Karger AG, BaselCalouste Gulbenkian Foundation; L'Oreal; UNESCO; Foundation for Science and Technology (FCT, Portugal) [SFRH/BPD/78901/2011, SFRH/BD/23754/2005, SFRH/BD/38127/2007]; COMPETE; FEDER [PTDC/SAU-NEU/102612/2008]info:eu-repo/semantics/publishedVersio

Nitric oxide from inflammatory origin impairs neural stem cell proliferation by inhibiting epidermal growth factor receptor signaling

Neuroinflammation is characterized by activation of microglial cells, followed by production of nitric oxide (NO), which may have different outcomes on neurogenesis, favoring or inhibiting this process. In the present study, we investigated how the inflammatory mediator NO can affect proliferation of neural stem cells (NSCs), and explored possible mechanisms underlying this effect. We investigated which mechanisms are involved in the regulation of NSC proliferation following treatment with an inflammatory stimulus (lipopolysaccharide plus IFN-gamma), using a culture system of subventricular zone (SVZ)-derived NSCs mixed with microglia cells obtained from wild-type mice (iNOS(+/+)) or from iNOS knockout mice (iNOS(-/-)). We found an impairment of NSC cell proliferation in iNOS(+/+) mixed cultures, which was not observed in iNOS(-/-) mixed cultures. Furthermore, the increased release of NO by activated iNOS(+/+) microglial cells decreased the activation of the ERK/MAPK signaling pathway, which was concomitant with an enhanced nitration of the EGF receptor. Preventing nitrogen reactive species formation with MnTBAP, a scavenger of peroxynitrite (ONOO-), or using the ONOO- degradation catalyst FeTMPyP cell proliferation and ERK signaling were restored to basal levels in iNOS(+/+) mixed cultures. Moreover, exposure to the NO donor NOC-18 (100 mu M), for 48 h, inhibited SVZ-derived NSC proliferation. Regarding the antiproliferative effect of NO, we found that NOC-18 caused the impairment of signaling through the ERK/MAPK pathway, which may be related to increased nitration of the EGF receptor in NSC. Using MnTBAP nitration was prevented, maintaining ERK signaling, rescuing NSC proliferation. We show that NO from inflammatory origin leads to a decreased function of the EGF receptor, which compromised proliferation of NSC. We also demonstrated that NO-mediated nitration of the EGF receptor caused a decrease in its phosphorylation, thus preventing regular proliferation signaling through the ERK/MAPK pathway.Foundation for Science and Technology, (FCT, Portugal); COMPETE; FEDER [PEst-C/SAU/LA0001/2013-2014, PEst-OE/EQB/LA0023/2013-2014, PTDC/SAU-NEU/102612/2008, PTDC/NEU-OSD/0473/2012]; FCT, Portugal [SERH/BPD/78901/2011, SERH/BD/38127/2007, SFRH/BD/77903/2011, SFRH/BD/79308/2011]info:eu-repo/semantics/publishedVersio

Motivation and physical activity in COPD: An exploratory study

A key factor for the adoption of an active lifestyle is self-determined motivation; however, it is often overlooked in COPD. Understanding the motives underlying patients’ decision to be (or not) physically active will provide insight into future interventions. This study assessed the motives for patients with COPD to engage in physical activity (PA) and their association with PA behaviour. A cross-sectional study was conducted in stable patients with COPD. Motivation was assessed with the Exercise Motivation Inventory-2 (EMI-2; score 0[Not at all true for me]–5[Very true for me]; 5 dimensions) and PA with accelerometry [ActiGraph-GT3X+, 7 days; moderate to vigorous PA (MVPA), steps/day]. Spearman’s correlations (ρ) were used to assess their relationship. 60 participants were enrolled (67.2±7.7 years; 76.7% men; FEV1 49.5±19.7pp). Patients’ motives to be physically active were mostly Health, Fitness and Psychological. Correlations with PA were weak and non-significant (p>0.05) (Table 1). Patients with COPD value Health, Fitness and Psychological motives to be physically active, although these are not related to their PA behaviour. Findings highlight the complex nature of PA and the need to further explore factors influencing PA and motivation in this population.info:eu-repo/semantics/publishedVersio

What motivates patients with COPD to be physically active? A cross-sectional study

Motivation can be broadly defined as what moves people to act. Low motivation is a frequently reported factor for the reduced physical activity (PA) levels observed in patients with chronic obstructive pulmonary disease (COPD). This study assessed patients' motives to be physically active, according to three pulmonary rehabilitation (PR) participation groups (Never PR, Previous PR and Current PR) and explored whether these motives were related to the PA levels and clinical characteristics. The motives to be physically active were assessed with the Exercise Motivation Inventory-2 (EMI-2, 14 motivational factors, five dimensions) and PA with accelerometry (PA groups: 0.05) but having less symptoms and ≥two comorbidities were associated with higher scores in psychological/health and body-related motives, respectively (p < 0.05). The findings may encourage health professionals to actively explore with patients their motives to be physically active to individualise PA promotion.publishe