Assessing the efficacy of the 'Bicho De 7 Cabeças' B-learning school-based program in enhancing mental health literacy and reducing stigma.

The prevalence of mental disorders in adolescents has a considerable impact on daily life, restricting tasks and diminishing overall quality of life while potentially leading to stigmatization. This study aims to measure the impact of a mental health literacy intervention program, called "Bicho de 7 Cabeças" project, in b-learning format, on the increase of knowledge and the decrease of stigma in young people from Póvoa de Varzim, in Portugal. A quasi-experimental study was conducted, from November 2022 to May 2023, involving an experimental group ("Bicho de 7 Cabeças" protocol) and an active control group (informational brochures), utilizing a pre-test/post-test design. Mental Health Literacy Measure-MHLM, Mental Health Promoting Knowledge Scale-MHPK-10, Mental Illness Knowledge Schedule-MAKS, Reported and Intended Behaviour Scale-RIBS, and Community Attitudes toward People with Mental Illness-CAMI were used. A total of 504 young students from the 9th grade enroll in this study, with a mean age around 14 years old. There is a significant difference between stigma (p <.001) and knowledge (p <.001) scores at baseline and follow-up. The results of this study shows that interventions aimed at young people for the promotion of mental health literacy and stigma reduction are needed and more initiatives should be implemented in schools to address these problems.

The therapeutic benefit of upgrade to cardiac resynchronization therapy in patients with pacing-induced cardiomyopathy.

Background: Pacing-induced cardiomyopathy (PICM) is an important cause of heart failure in patients with a right ventricular pacing burden. Recent evidence suggests that an upgrade to cardiac resynchronization therapy (CRT) may confer benefit in PICM. Objective: To assess the extent and identify predictors of improvement following upgrade to CRT in patients with PICM. Methods: We retrospectively analyzed 43 patients undergoing CRT upgrade for PICM over the 10-year period of 2011 to 2021 at our center. All patients with PICM who underwent device upgrade from a dual- or single-chamber ventricular pacemaker to CRT were included. PICM was defined as a decrease of ≥10% in left ventricular ejection fraction (LVEF), resulting in an LVEF <50% among patients with ≥20% Right ventricular pacing burden without an alternative cause for cardiomyopathy. Results: LVEF significantly improved from 28.7% preupgrade to 44.3% post-CRT upgrade (P < .01). Of 37 patients with severe LV dysfunction, 34 (91.9%) improved to an LVEF >35% and 13 (35.1%) improved to an LVEF >50%. The LV end-diastolic diameter decreased from 5.9 cm preupgrade to 5.4 cm postupgrade (P < .01). Using linear regression, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use was associated with significant LVEF improvement (+7.21%, P = .05). We observed a low rate of complications, and 1 in 4 CRT upgrades required venoplasty (n = 10 of 43, 23.3%). Conclusion: We provide further evidence for the benefit of CRT upgrade in the management of patients with PICM.

Mental Health Literacy and Stigma in a Municipality in the North of Portugal: A Cross-Sectional Study.

Portugal has Europe's second-highest prevalence of psychiatric illnesses, and this is the reason why mental health literacy (MHL) and stigma should be addressed. This study aimed to investigate the mental health literacy and stigma levels among different groups of people from Póvoa de Varzim, a municipality in the north of Portugal. Students, retired people, and professionals (education, social, and healthcare fields) were recruited using a convenience sample from June to November 2022. Participants' MHL levels were evaluated using the Mental Health Promoting Knowledge Scale (MHPK), Mental Health Literacy Measure (MHLM) and Mental Health Knowledge Schedule (MAKS). Stigma levels were evaluated using Community Attitudes towards Mental Illness (CAMI) and the Reported and Intended Behaviour Scale (RIBS). A total of 928 questionnaires were filed. The respondents included 65.70% of women, a mean age of 43.63 (±26.71) years and 9.87 (±4.39) years of school education. MHL increased with age, education level and was higher in women (p < 0.001). A higher level of MHL was seen in health professionals (p < 0.001). Findings revealed that older people stigmatized people with mental illness more (p < 0.001), and the female gender stigmatize less (p < 0.001). In addition, results showed that stigma decreased with higher mental health literacy (r between 0.11 and 0.38; p < 0.001). To conclude, specific campaigns that promote mental health literacy should be tailored to specific profiles within this population to address those that have more stigma.

DESI-MSI-based technique to unravel spatial distribution of COMT inhibitor Tolcapone.

Ascertaining compound exposure and its spatial distribution are essential steps in the drug development process. Desorption electrospray ionization mass spectrometry (DESI-MSI) is a label-free imaging technique capable of simultaneously identify and visualize the distribution of a diverse range of biomolecules. In this study, DESI-MSI was employed to investigate spatial distribution of tolcapone in rat liver and brain coronal - frontal and striatal -sections after a single oral administration of 100 mg/Kg of tolcapone, brain-penetrant compound. Tolcapone was evenly distributed in liver tissue sections whereas in the brain it showed differential distribution across brain regions analyzed, being mainly located in the olfactory bulb, basal forebrain region, striatum, and pre-frontal cortex (PFC; cingulate, prelimbic and infralimbic area). Tolcapone concentration in tissues was compared using DESI-MSI and liquid-chromatography mass spectrometry (LC-MS/MS). DESI-MSI technique showed a higher specificity on detecting tolcapone in liver sections while in the brain samples DESI-MSI did not allow a feasible quantification. Indeed, DESI-MSI is a qualitative technique that allows to observe heterogeneity on distribution but more challenging regarding accurate measurements. Overall, tolcapone was successfully localized in liver and brain tissue sections using DESI-MSI, highlighting the added value that this technique could provide in assisting tissue-specific drug distribution studies.

Antimicrobial peptide-grafted PLGA-PEG nanoparticles to fight bacterial wound infections.

Wound infection treatment with antimicrobial peptides (AMPs) is still not a reality, due to the loss of activity in vivo. Unlike the conventional strategy of encapsulating AMPs on nanoparticles (NPs) leaving activity dependent on the release profile, this work explores AMP grafting to poly(D,L-lactide-co-glycolide)-polyethylene glycol NPs (PLGA-PEG NPs), whereby AMP exposition, infection targeting and immediate action are promoted. NPs are functionalized with MSI-78(4-20), an equipotent and more selective derivative of MSI-78, grafted through a thiol-maleimide (Mal) Michael addition. NPs with different ratios of PLGA-PEG/PLGA-PEG-Mal are produced and characterized, with 40%PLGA-PEG-Mal presenting the best colloidal properties and higher amounts of AMP grafted as shown by surface charge (+8.6 ± 1.8 mV) and AMP quantification (326 µg mL-1, corresponding to 16.3 µg of AMP per mg of polymer). NPs maintain the activity of the free AMP with a minimal inhibitory concentration (MIC) of 8-16 µg mL-1 against Pseudomonas aeruginosa, and 16-32 µg mL-1 against Staphylococcus aureus. Moreover, AMP grafting accelerates killing kinetics, from 1-2 h to 15 min for P. aeruginosa and from 6-8 h to 0.5-1 h for S. aureus. NP activity in a simulated wound fluid is maintained for S. aureus and decreases slightly for P. aeruginosa. Furthermore, NPs do not demonstrate signs of cytotoxicity at MIC concentrations. Overall, this promising formulation helps unleash the full potential of AMPs for the management of wound infections.

Endogenous GDNF Is Unable to Halt Dopaminergic Injury Triggered by Microglial Activation.

Overactivation of microglial cells seems to play a crucial role in the degeneration of dopaminergic neurons occurring in Parkinson's disease. We have previously demonstrated that glial cell line-derived neurotrophic factor (GDNF) present in astrocytes secretome modulates microglial responses induced by an inflammatory insult. Therefore, astrocyte-derived soluble factors may include relevant molecular players of therapeutic interest in the control of excessive neuroinflammatory responses. However, in vivo, the control of neuroinflammation is more complex as it depends on the interaction between different types of cells other than microglia and astrocytes. Whether neurons may interfere in the astrocyte-microglia crosstalk, affecting the control of microglial reactivity exerted by astrocytes, is unclear. Therefore, the present work aimed to disclose if the control of microglial responses mediated by astrocyte-derived factors, including GDNF, could be affected by the crosstalk with neurons, impacting GDNF's ability to protect dopaminergic neurons exposed to a pro-inflammatory environment. Also, we aimed to disclose if the protection of dopaminergic neurons by GDNF involves the modulation of microglial cells. Our results show that the neuroprotective effect of GDNF was mediated, at least in part, by a direct action on microglial cells through the GDNF family receptor α-1. However, this protective effect seems to be impaired by other mediators released in response to the neuron-astrocyte crosstalk since neuron-astrocyte secretome, in contrast to astrocytes secretome, was unable to protect dopaminergic neurons from the injury triggered by lipopolysaccharide-activated microglia. Supplementation with exogenous GDNF was needed to afford protection of dopaminergic neurons exposed to the inflammatory environment. In conclusion, our results revealed that dopaminergic protective effects promoted by GDNF involve the control of microglial reactivity. However, endogenous GDNF is insufficient to confer dopaminergic neuron protection against an inflammatory insult. This reinforces the importance of further developing new therapeutic strategies aiming at providing GDNF or enhancing its expression in the brain regions affected by Parkinson's disease.

The Antidiabetic Effect of Grape Pomace Polysaccharide-Polyphenol Complexes.

Type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic metabolic diseases of the 21st century. Nevertheless, its prevalence might be attenuated by taking advantage of bioactive compounds commonly found in fruits and vegetables. This work is focused on the recovery of polyphenols and polysaccharide-polyphenol conjugates from grape pomace for T2DM management and prevention. Bioactives were extracted by solid-liquid extraction and by pressurized hot water extraction (PHWE). Polyphenolic fraction recovered by PHWE showed the highest value for total phenolic content (427 µg GAE.mg-1), mainly anthocyanins and proanthocyanidins, and higher antioxidant activity compared to the fraction recovered by solid-liquid extraction. Polysaccharide-polyphenol conjugates comprehended pectic polysaccharides to which approximately 108 µg GAE of phenolic compounds (per mg fraction) were estimated to be bound. Polyphenols and polysaccharide-polyphenol conjugates exhibited distinct antidiabetic effects, depending on the extraction methodologies employed. Extracts were particularly relevant in the inhibition of a-glucosidase activity, with free polyphenols showing an IC50 of 0.47 µg.mL-1 while conjugates showed an IC50 of 2.7, 4.0 and 5.2 µg.mL-1 (solid-liquid extraction, PHWE at 95 and 120 °C, respectively). Antiglycation effect was more pronounced for free polyphenols recovered by PHWE, while the attenuation of glucose uptake by Caco-2 monolayers was more efficient for conjugates obtained by PHWE. The antidiabetic effect of grape pomace bioactives opens new opportunities for the exploitation of these agri-food wastes in food nutrition, the next step towards reaching a circular economy in grape products.

Characterization of a Parkinson's disease rat model using an upgraded paraquat exposure paradigm.

Animal models of human diseases are crucial experimental tools to investigate the mechanisms involved in disease pathogenesis and to develop new therapies. In spite of the numerous animal models currently available that reproduce several neuropathological features of Parkinson disease (PD), it is challenging to have one that consistently recapitulates human PD conditions in both motor behaviors and biochemical pathological outcomes. Given that, we have implemented a new paradigm to expose rats to a chronic low dose of paraquat (PQ), using osmotic minipumps and characterized the developed pathologic features over time. The PQ exposure paradigm used lead to a rodent model of PD depicting progressive nigrostriatal dopaminergic neurodegeneration, characterized by a 41% significant loss of dopaminergic neuron in the substantia nigra pars compacta (SNpc), a significant decrease of 18% and 40% of dopamine levels in striatum at week 5 and 8, respectively, and a significant 1.5-fold decrease in motor performance. We observed a significant increase of microglia activation state, sustained levels of α-synucleinopathy and increased oxidative stress markers in the SNpc. In summary, this is an explorative study that allowed to characterize an improved PQ-based rat model that recapitulates cardinal features of PD and may represent an attractive tool to investigate several mechanisms underlying the various aspects of PD pathogenesis as well as for the validation of the efficacy of new therapeutic approaches that targets different mechanisms involved in PD neurodegeneration.

Acute salt loading induces sympathetic nervous system overdrive in mice lacking salt-inducible kinase 1 (SIK1).

Loss of salt-inducible kinase 1 (SIK1) triggers an increase in blood pressure (BP) upon a chronic high-salt intake in mice. Here, we further addressed the possible early mechanisms that may relate to the observed rise in BP in mice lacking SIK1. SIK1 knockout (sik1-/-) and wild-type (sik1+/+) littermate mice were challenged with either a high-salt (8% NaCl) or control (0.3% NaCl) diet for 7 days. Systolic BP was significantly increased in sik1-/- mice after 7 days of high-salt diet as compared with sik1+/+ mice and to sik1-/- counterparts on a control diet. The renin-angiotensin-aldosterone system and the sympathetic nervous system were assayed to investigate possible causes for the increase in BP in sik1-/- mice fed a 7-day high-salt diet. Although no differences in serum renin and angiotensin II levels were observed, a reduction in aldosterone serum levels was observed in mice fed a high-salt diet. Urinary L-DOPA and noradrenaline levels were significantly increased in sik1-/- mice fed a high-salt diet as compared with sik1-/- mice on a control diet. Similarly, the activity of dopamine ß-hydroxylase (DßH), the enzyme that converts dopamine to noradrenaline, was significantly increased in the adrenal glands of sik1-/- mice on a high-salt intake compared with sik1+/+ and sik1-/- mice on a control diet. Treatment with etamicastat (50 mg/kg/day), a peripheral reversible DßH inhibitor, administered prior to high-salt diet, completely prevented the systolic BP increase in sik1-/- mice. In conclusion, SIK1 activity is necessary to prevent the development of salt-induced high blood pressure and associated SNS overactivity.

Sellar plasmacytoma presenting with symptoms of anterior pituitary dysfunction.

Sellar plasmacytomas are rare and the differential diagnosis with non-functioning pituitary adenomas might be difficult because of clinical and radiological resemblance. They usually present with neurological signs and intact anterior pituitary function. Some may already have or eventually progress to multiple myeloma. We describe a case associated with extensive anterior pituitary involvement, which is a rare form of presentation. A 68-year-old man was referred to our Endocrinology outpatient clinic due to gynecomastia, reduced libido and sexual impotence. Physical examination, breast ultrasound and mammography confirmed bilateral gynecomastia. Blood tests revealed slight hyperprolactinemia, low testosterone levels, low cortisol levels and central hypothyroidism. Sellar MRI showed a heterogeneous sellar mass (56 × 60 × 61 mm), initially suspected as an invasive macroadenoma. After correcting the pituitary deficits with hydrocortisone and levothyroxine, the patient underwent transsphenoidal surgery. Histological examination revealed a plasmacytoma and multiple myeloma was ruled out. The patient was unsuccessfully treated with radiation therapy (no tumor shrinkage). Myeloma ultimately developed, with several other similar lesions in different locations. The patient was started on chemotherapy, had a bone marrow transplant and is now stable (progression free) on lenalidomide and dexamethasone. The presenting symptoms and panhypopituitarism persisted, requiring chronic replacement treatment with levothyroxine, hydrocortisone and testosterone. LEARNING POINTS: Plasmacytomas, although rare, are a possible type of sellar masses, which have a completely different treatment approach, so it is important to make the correct diagnosis.Usually, they present with neurological signs and symptoms and a well-preserved pituitary function, but our case shows that anterior pituitary function can be severely compromised.Making a more extensive evaluation (clinical and biochemical) might provide some clues to this diagnosis.

Effect of Levodopa on Reward and Impulsivity in a Rat Model of Parkinson's Disease.

The use of dopamine replacement therapies (DRT) in the treatment of Parkinson's disease (PD) can lead to the development of dopamine dysregulation syndrome (DDS) and impulse control disorders (ICD), behavioral disturbances characterized by compulsive DRT self-medication and development of impulsive behaviors. However, the mechanisms behind these disturbances are poorly understood. In animal models of PD, the assessment of the rewarding properties of levodopa (LD), one of the most common drugs used in PD, has produced conflicting results, and its ability to promote increased impulsivity is still understudied. Moreover, it is unclear whether acute and chronic LD therapy differently affects reward and impulsivity. In this study we aimed at assessing, in an animal model of PD with bilateral mesostriatal and mesocorticolimbic degeneration, the behavioral effects of LD therapy regarding reward and impulsivity. Animals with either sham or 6-hydroxydopamine (6-OHDA)-induced bilateral lesions in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) were exposed to acute and chronic LD treatment. We used the conditioned place preference (CPP) paradigm to evaluate the rewarding effects of LD, whereas impulsive behavior was measured with the variable delay-to-signal (VDS) task. Correlation analyses between behavioral measurements of reward or impulsivity and lesion extent in SNc/VTA were performed to pinpoint possible anatomical links of LD-induced behavioral changes. We show that LD, particularly when administered chronically, caused the development of impulsive-like behaviors in 6-OHDA-lesioned animals in the VDS. However, neither acute or chronic LD administration had rewarding effects in 6-OHDA-lesioned animals in the CPP. Our results show that in a bilateral rat model of PD, LD leads to the development of impulsive behaviors, strengthening the association between DRT and DDS/ICD in PD.

GPER activation is effective in protecting against inflammation-induced nigral dopaminergic loss and motor function impairment.

Increasing evidence suggest that excessive inflammatory responses from overactivated microglia play a critical role in Parkinson's disease (PD), contributing to, or exacerbating, nigral dopaminergic (DA) degeneration. Recent results from our group and others demonstrated that selective activation of G protein-coupled estrogen receptor (GPER) with the agonist G1 can protect DA neurons from 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxins. However, it is not known whether modulation of microglial responses is one of the mechanisms by which G1 exerts its DA neuroprotective effects. We analyzed, in the N9 microglial cell line, the effect of G1 on microglial activation induced by lipopolysaccharide (LPS) exposure. The results revealed that G1 significantly decrease phagocytic activity, expression of inducible nitric oxide synthase (iNOS) and release of nitric oxide (NO) induced by LPS. To determine the relevance of this anti-inflammatory effect to the protection of nigral DA cells, the effect of G1 was analyzed in male mice injected unilaterally in the substantia nigra (SN) with LPS. Although G1 treatment did not decrease LPS-induced increase of ionized calcium binding adaptor molecule 1 (iba-1) positive cells it significantly reduced interleukin-1beta (IL-1ß), cluster of differentiation 68 (CD68) and iNOS mRNA levels, and totally inhibited nigral DA cell loss and, as a consequence, protected the motor function. In summary, our findings demonstrated that the G1 agonist is able to modulate microglial responses and to protect DA neurons and motor functions against a lesion induced by an inflammatory insult. Since G1 lacks the feminizing effects associated with agonists of the classical estrogen receptors (ERs), the use of G1 to selectively activate the GPER may be a promising strategy for the development of new therapeutics for the treatment of PD and other neuroinflammatory diseases.

Role of Neurotrophic Factors in Parkinson's Disease.

Parkinson's disease is an age-associated progressive neurodegenerative disorder that has gained crescent social and economic impact due to the aging of the western society. All current therapies are symptomatic and fail to reverse or halt the progression of dopaminergic neurons loss. The discovery of the capability of neurotrophic factors to protect these neurons lead numerous research groups to focus their efforts in developing therapies aiming at promoting the control of Parkinson´s disease through the delivery of neurotrophic factors to the brain or by boosting their endogenous levels. Both strategies were successful in inducing protection of dopaminergic neurons and motor recovery in preclinical models of the disease. Contrariwise, very limited success was obtained in clinical studies, where glial cell line-derived neurotrophic factor and neurturin were the neurotrophic factors of choice for Parkinson's disease therapy. These drawbacks motivate the development of novel forms of delivery or the modification of the injected molecules aiming at providing a more stable and effective administration with improved diffusion in the target tissue, and without the immune responses observed in the earliest clinical studies. Although promising results were obtained with some of these new approaches performed in experimental models of the disease, they were not yet tested in human studies. In this review, we present the current knowledge on neurotrophic factors and their role in Parkinson's disease, focusing on the strategies that have been developed to increase their levels in target areas of the brain to achieve protection of dopaminergic neurons and motor behaviour recovery.

Directrices prácticas para programas de apoyo entre personas con enfermedad mental / Practical guidelines for peer support programmes for mental health problems

Introducción. Este estudio tiene como objetivo determinar los principios orientadores para la implementación de programas de apoyo entre personas con problemas de salud mental en Portugal. Material y métodos. Este estudio ha sido dividido en 2 fases. En la primera se realizó una revisión sistemática de 112 artículos indexados en las bases de datos de ISI y EBSCO (2001-2012). En la segunda fase se llevó a cabo un panel con metodología Delphi y 2 rondas formado por profesionales, investigadores y personas con problemas de salud mental. El objetivo era analizar los enunciados generados a partir de la revisión sistemática previa. Los datos fueron analizados con NVivo 9 y SPSS 19. Resultados. Durante la ronda Delphi participaron inicialmente 72 expertos, de los cuales 44 participaron en la segunda ronda. Se alcanzó un consenso del 84% sobre las principales afirmaciones. A partir de estos resultados, se destacan 8 ámbitos principales que cubren las siguientes áreas: objetivos de apoyo de los iguales, selección de los proveedores de apoyo, capacitación y acreditación, papel de los profesionales de salud mental, papel de los proveedores de apoyo, acceso a los proveedores de apoyo, cuidado de los proveedores de apoyo, y programa de evaluación. Conclusiones. El apoyo de iguales aplicado a la enfermedad mental está todavía poco explorado y rodeado de cierta controversia y ambigüedad. Sin embargo, si cuenta con una buena organización y supervisión parece mejorar la calidad de vida y la inclusión social de las personas con enfermedad mental. Este hecho demuestra la importancia de realizar estudios que incrementen nuestro conocimiento acerca de dichos programas y se elaboren directrices para su aplicación. Este consenso nacional se puede utilizar como punto de partida para el diseño e implementación de programas de apoyo de iguales en las organizaciones de salud mental (AU)

Introduction. This study aims to determine the guiding principles for the implementation of peer support programmes in Portugal. Material and methods. The study was divided in 2 phases. In the first phase a systematic review of 112 papers indexed in ISI and EBSCO databases (2001 to 2012) was conducted. In the second phase clinicians, researchers, and people with psychiatric disabilities were invited to take part in a two-round online survey based on the Delphi process to rate the importance of statements generated from the systematic review. Data were analysed with NVivo 9 and SPSS 19. Results. During the Delphi round 72 experts were contacted, 44 participated in the second round. A consensus was achieved on major statements, with 84% of the sentences obtaining a consensus and 8 key recommendations covering goals of peer support, selection of peer supporters, training and accreditation, role of mental health professionals, role of peer supporters, access to peer supporters, looking after peer supporters, and programme evaluation were based on these statements. Conclusions. Use of peer support for mental health problems is still underexplored and surrounded by some controversy and ambiguity. However, its organization and proper monitoring appears to enhance the quality of life and social inclusion of people with mental illness. This highlights the importance of conducting studies that increase our knowledge of these programmes and determining guidelines for their implementation. This national consensus may be used as a starting point for the design and implementation of peer support programmes in mental health organizations (AU)

[Practical guidelines for peer support programmes for mental health problems]. / Directrices prácticas para programas de apoyo entre personas con enfermedad mental.

INTRODUCTION: This study aims to determine the guiding principles for the implementation of peer support programmes in Portugal. MATERIAL AND METHODS: The study was divided in 2 phases. In the first phase a systematic review of 112 papers indexed in ISI and EBSCO databases (2001 to 2012) was conducted. In the second phase clinicians, researchers, and people with psychiatric disabilities were invited to take part in a two-round online survey based on the Delphi process to rate the importance of statements generated from the systematic review. Data were analysed with NVivo 9 and SPSS 19. RESULTS: During the Delphi round 72 experts were contacted, 44 participated in the second round. A consensus was achieved on major statements, with 84% of the sentences obtaining a consensus and 8 key recommendations covering goals of peer support, selection of peer supporters, training and accreditation, role of mental health professionals, role of peer supporters, access to peer supporters, looking after peer supporters, and programme evaluation were based on these statements. CONCLUSIONS: Use of peer support for mental health problems is still underexplored and surrounded by some controversy and ambiguity. However, its organization and proper monitoring appears to enhance the quality of life and social inclusion of people with mental illness. This highlights the importance of conducting studies that increase our knowledge of these programmes and determining guidelines for their implementation. This national consensus may be used as a starting point for the design and implementation of peer support programmes in mental health organizations.

GPER: A new tool to protect dopaminergic neurons?

Parkinson's disease (PD) is characterized by a selective degeneration of nigrostriatal dopaminergic pathway. Epidemiological studies revealed a male predominance of the disease that has been attributed to the female steroid hormones, mainly the estrogen. Estrogen neuroprotective effects have been shown in several studies, however the mechanisms responsible by these effects are still unclear. Previous data from our group revealed that glial cell line-derived neurotrophic factor (GDNF) is crucial to the dopaminergic protection provided by 17ß-estradiol, and also suggest that the intracellular estrogen receptors (ERs) are not required for that neuroprotective effects. The present study aimed to investigate the contribution of the G protein-coupled ER (GPER) activation in estrogen-mediated dopaminergic neuroprotection against an insult induced by 1-methyl-4-phenylpyridinium (MPP(+)), and whether GPER neuroprotective effects involve the regulation of GDNF expression. Using primary mesencephalic cultures, we found that GPER activation protects dopaminergic neurons from MPP(+) toxicity in an extent similar to the promoted by a 17ß-estradiol. Moreover, GPER activation promotes an increase in GDNF levels. Both, GDNF antibody neutralization or RNA interference-mediated GDNF knockdown prevented the GPER-mediated dopaminergic protection verified in mesencephalic cultures challenged with MPP(+). Overall, these results revealed that G1, a selective agonist of GPER, is able to protect dopaminergic neurons and that GDNF overexpression is a key feature to GPER induced the neuroprotective effects.

Peer support for people with mental illness / Suporte interpares na doença mental

Background Peer support is a mutual aid system based on the belief that someone who faced/overcome adversity can provide support, encouragement and guidance to those who experience similar situations. Objective: To conduct a systematic review that describes this concept and characterizes peer supporters, its practice and efficacy. Method: Research on ISI Web of Science, EBSCO Psychology and Behavioral Sciences Collection and Medline databases (from 2001 to December 2013) was conducted using as keywords “mental illness”, “mental health”, “psychiatric disability”, “mental health services”, combined with “peer support”, “mutual support”, “self-help groups”, “consumers as providers”, “peer-run services”, “peer-run programs” and “social support”. Results: We found 1,566 articles and the application of both the exclusion (studies with children, teenagers and elderly people; disease in comorbidity; peer support associated to physical illnesses or family members/caregivers) and the inclusion criteria (full text scientific papers, peer support or similar groups directed for schizophrenia, depression, bipolar or psychotic disorders) lead to 165 documents, where 22 were excluded due to repetition and 31 to incomplete text. We analyzed 112 documents, identifying as main peer support categories: characterization, peer supporter, practices and efficacy. Discussion Despite an increasing interest about this topic, there is no consensus, suggesting realizing more studies...

Contexto: O suporte interpares é um sistema de ajuda mútua baseado na crença de que alguém que enfrentou/superou adversidades pode oferecer apoio, encorajamento e orientação a outros que enfrentam situações similares. Objetivo: Realizar uma revisão sistemática que caracterize o suporte interpares como prática, analise a sua eficácia e caracterize os pares prestadores de suporte interpares. Método: Pesquisa nas bases de dados ISI Web of Science, EBSCO Psychology and Behavioral Sciences Collection e Medline (2001 a dezembro de 2013), utilizando as palavras-chave “mental illness”, “mental health”, “psychiatric disability”, “mental health services”, combinadas com “peer support”, “mutual support”, “self-help groups”, “consumers as providers”, “peer-run services”, “peer-run programs” e “social support”. Resultados: Encontraram-se 1.566 artigos e foram aplicados os critérios de exclusão (artigos com crianças, adolescentes e idosos; doença mental em comorbidade; suporte interpares em doenças físicas ou familiares/cuidadores) e de inclusão (revistas científicas com texto integral disponível; suporte interpares ou grupos similares dirigidos a esquizofrenia, depressão, transtorno bipolar e outras perturbações psicóticas), resultando em 165 documentos. Excluíram-se 22 por repetição e 31 por texto incompleto, resultando em 112, os quais se identificaram como principais categorias do suporte interpares: caracterização, prestador de suporte, práticas e eficácia. Conclusão: Existe interesse crescente pelo tema, embora alguns domínios não sejam consensuais, sugerindo necessidade de mais estudos...

Rodent models of Parkinson's disease: beyond the motor symptomatology.

Parkinson's disease (PD) is classically characterized by motor symptoms; however, non-motor symptoms (NMS) are increasingly recognized as relevant in disease-state, given the associated alterations in mood (depression and anxiety) and cognition. Here, particularly in regards to NMS, we aimed to compare the motor, emotional and cognitive behavior of three animal models of PD that trigger dopaminergic (DAergic) degeneration on both brain hemispheres: (i) the 6-hydroxydopamine (6-OHDA, 8 or 6 µg) lesion model; (ii) the paraquat (PQ) induced model, and (iii) a genetic model based on α-synuclein overexpression (α-syn). 6-OHDA and α-syn vector were injected bilaterally in the substantia nigra pars compacta (SNpc) of adult male Wistar rats; as for PQ delivery, micro-osmotic pumps were implanted in the interscapular region. Motor deficits were observed in all models, with histological analysis of tyrosine hydroxylase positive cells in the SNpc revealing a significant loss of DAergic neurons in all animal models. In addition, the α-syn animal model also presented a reduction in exploratory activity, and the 6-OHDA and PQ animals displayed a significant increase in both depressive- and anxiety-like behavior. Interestingly, cognitive impairment (working memory) was only observed in the 6-OHDA model. Overall, these PD models are suitable for mimicking the motor symptoms associated to PD, with each encompassing other relevant NMS components of the disorder that may prove beneficial for further studies in PD.

Neudesin is involved in anxiety behavior: structural and neurochemical correlates.

Neudesin (also known as neuron derived neurotrophic factor, Nenf) is a scarcely studied putative non-canonical neurotrophic factor. In order to understand its function in the brain, we performed an extensive behavioral characterization (motor, emotional, and cognitive dimensions) of neudesin-null mice. The absence of neudesin leads to an anxious-like behavior as assessed in the elevated plus maze (EPM), light/dark box (LDB) and novelty suppressed feeding (NSF) tests, but not in the acoustic startle (AS) test. This anxious phenotype is associated with reduced dopaminergic input and impoverished dendritic arborizations in the dentate gyrus granule neurons of the ventral hippocampus. Interestingly, shorter dendrites are also observed in the bed nucleus of the stria terminalis (BNST) of neudesin-null mice. These findings lead us to suggest that neudesin is a novel relevant player in the maintenance of the anxiety circuitry.