Avaliação da resposta neurogénica à ativação do recetor de estradiol acoplado à proteína G (GPER)

Estradiol is a steroid hormone that plays an important trophic and protective role in the adult brain, being essential not only to maintaining normal brain functions but also to protect the brain against neural injuries. There is an increasing number of studies that evidence the neuroprotective effect of estradiol, namely through the activation of the G protein-coupled estrogen receptor (GPER). However, it is not known if this protective effect involve a pro-neurogenic action of this receptor. Therefore, the aim of this study was to evaluate whether GPER activation triggers a neurogenic response in the subventricular zone (SVZ), a neurogenic niche. We confirmed the presence of GPER both in neural stem cell (NSC) cultures from SVZ and in the cells present in the borders of the lateral ventricles of mice brain, where SVZ is located. We analyse the effects evoked by GPER activation in vitro, using G1, the GPER specific agonist. GPER activation promoted a significant increase in the expression levels of the receptor as well as an increase of NSC differentiation into mature neurons and glial cells, assessed by the number of Ki67+/Neuronal nuclei (NeuN+) and Ki67+/Glial fibrillary acidic protein (GFAP+)- positive cells, respectively. Contrariwise, GPER activation did not increase neuroblast (Ki67+/ Doublecortin (DCX+)) or glial (Ki67+/DCX-) proliferation in vitro, in contrast estradiol significantly promoted neural cell proliferation. The in vivo analysis of GPER activation showed that G1 per se was able to increase neural proliferation in the mice SVZ. Taken together, the results showed that GPER activation effectively promote neurogenesis in the SVZ and has potential to be used as a neurogenic therapeutic agent.O estradiol pertence ao grupo das hormonas esteroides e desempenha um papel importante, sendo essencial não só na manutenção das funções normais do cérebro, mas também na proteção contra lesões neurais. São cada vez mais os estudos que evidenciam o efeito neuroprotetor do estradiol, nomeadamente através da ativação do recetor de estrogénio acoplado à proteína G (GPER). No entanto, não se sabe se esses efeitos neuroprotetores envolvem uma ação pró-neurogénica deste recetor. Assim, o objetivo deste estudo foi avaliar se a ativação do GPER é capaz de desencadear uma resposta neurogénica na região subventricular (SVZ). Foi confirmada a presença do GPER em culturas de células estaminais neurais (NSC) isoladas a partir da SVZ, assim como em fatias de SVZ obtidas de murganhos. A estimulação de culturas de NSC derivadas de SVZ com agonistas do GPER (G1) desencadeou um aumento significativo dos níveis de expressão do recetor bem como um aumento da diferenciação de NSC em neurónios e células da glia, avaliadas através do número de células positivas para Ki67+/ Neuronal nuclei (NeuN+) e Ki67+/ Glial fibrillary acidic protein (GFAP+), respetivamente. Pelo contrário, a ativação seletiva do GPER não aumentou o número de neuroblastos (Ki67+/ Doublecortin (DCX+)) ou células da glia (Ki67+/DCX-) proliferativos, diferindo do efeito mediado pelo estradiol, o qual aumentou significativamente a proliferação de células neurais. A injeção subcutânea de murganhos com G1 (190µg/Kg) e intraperitoneal com Bromodeoxiuridina (BrdU) mostrou que o G1, per se, aumenta a proliferação neural na SVZ de murganhos. Em conjunto, os nossos resultados sugerem que a ativação do GPER promove a neurogénese na SVZ, apresentando elevado potencial para ser utilizado como uma estratégia regeneradora

Clinical diagnostic criteria have a high impact on the frequency of dementia in late-stage Parkinson's disease

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Background: Cognitive impairment is a potential late feature of Parkinson's disease (PD). However, studies in patients with late-stage PD are lacking due to the particular characteristics of this population.Objectives: To evaluate the frequency of dementia in late-stage PD patients and to assess the impact of using different diagnostic criteria.Methods: We conducted a cross-sectional study to estimate the frequency of dementia in late-stage PD patients using the International Parkinson and Movement Disorders Society (MDS) (Level II) clinical diagnostic criteria as the primary outcome. We also applied other diagnostic criteria [MDS (Level I), DSM-IV, and DSM-5 criteria] to determine their applicability and impact on dementia frequency.Results: 93 participants with a mean age of 75.8 years (SD 6.8) and 16.5 years (SD 7.5) of disease duration were included. 64.3% were classified as demented using the International Parkinson and Movement Disorders Society (MDS) (Level II) clinical diagnostic criteria. We observed a high discrepancy on the frequency of dementia depending on the criteria applied [6.2% with MDS (Level I), 58.8% with DSM-IV, and 72.0% with DSM-5 criteria].Conclusions: We found a frequency of dementia below what was observed in similar populations. The particular characteristics of our sample may have contributed as protective factors for late-stage dementia. Dementia frequency varied depending on the criteria used mainly due to the presence of major depression.info:eu-repo/semantics/publishedVersio

High frequency of psychosis in late-stage Parkinsońs disease.

BACKGROUND: Psychosis is a frequent non-motor symptom in Parkinson's disease (PD). Estimates of the frequency of Parkinsońs disease psychosis (PDP) vary widely. Knowledge about the frequency and phenomenology of psychosis in late-stage (LS) PD patients is limited.This study aimed to determine the frequency of psychosis in LSPD patients through clinical diagnostic interview (CDI) (gold standard), according to NINDS/NIMH diagnostic criteria for PDP. The secondary objectives were to characterize the phenomenology, to test selected instruments and assess their adequacy in comparison to CDI, and to assess the psychiatric comorbidities. METHODS: A cross-sectional study including LSPD patients (patients with ≥ 7 years from symptoms onset and Hoehn and Yahr scale score > 3 or a Schwab and England scale score < 50% in the ON condition) was conducted. Patients were subjected to psychiatric, neurological, and neuropsychological evaluations. Each patient was interviewed by a psychiatrist who performed a CDI. RESULTS: 92 LSPD patients were included. 55.4% experienced psychotic symptoms according to NINDS/NIMH diagnostic criteria for PDP. Hallucinations were present in 94.1% and delusions in 29.4% of the psychotic patients. Visual hallucinations were the most common (88.23%) psychotic symptom. 72.5% of LSPD patients with psychotic symptoms had at least one comorbid psychiatric diagnosis. Lower frequency of psychosis was found when the assessment was performed only through selected instruments rather than CDI. CONCLUSIONS: A high frequency (55.4%) of psychotic symptoms and comorbid psychiatric (72.5%) diagnosis were found in LSPD patients. The use of CDI, in addition to structured scales may increase the sensitivity of detecting psychotic symptoms

Profile of cognitive impairment in late‐stage Parkinson's disease

© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Introduction: The profile of cognitive impairment associated with the late stages of Parkinson's disease (LSPD) is rarely reported. Its characterization is necessary to better understand the cognitive changes that occur as the disease progresses and to better contribute to its management. Methods: In this cross-sectional study, we characterized the cognitive profile of LSPD patients using the comprehensive assessment methodology proposed by the International Parkinson and Movement Disorders Society Task Force. The association of clinical and demographic variables with dementia diagnosis was also investigated using binary logistic regression analysis. Results: Eighty-four LSPD patients were included (age 75.4 ± 6.9; disease duration 16.9 ± 7.5). Fifty-four (64.3%) were classified as demented and presented a global impairment cognitive profile. In the nondemented group (N = 30), 25 (83.3%) LSPD patients met the diagnostic criteria for mild cognitive impairment, mostly with multiple domain impairment (96.0%) and a heterogeneous profile. Memory was the most frequent and severely impaired cognitive domain in both groups. Disease disability, orientation, complex order comprehension, verbal learning, and visuoconstructive abilities were significantly associated with dementia diagnosis (p < .05). Conclusions: Cognitive impairment in multiple domains was common in LSPD patients. The most frequent and prominent deficits were in the memory domain, with a strong interference from attention impairment. Disease disability, orientation, complex order comprehension, verbal learning, and visuoconstructive abilities proved to be important determinants for dementia diagnosis.This work was supported by a doctoral fellowship (SFRH/BD/139853/2018) from Fundação para a Ciência e Tecnologia, Portugal, which was assigned to Catarina Severiano e Sousa.info:eu-repo/semantics/publishedVersio

Boletín meteorológico diario: Número 267 - 1980 Septiembre 23

Introduction: A growing body of evidence suggests that bipolar disorder (BD) is a progressive disease according to clinical, biochemical and neuroimaging findings. This study reviewed the literature on the relationship between specific biomarkers and BD stages. Methods: A comprehensive literature search of MEDLINE and PubMed was conducted to identify studies in English and Portuguese using the keywords biomarker, neurotrophic factors, inflammation, oxidative stress, neuroprogression and staging models cross-referenced with bipolar disorder. Results: Morphometric studies of patients with BD found neuroanatomic abnormalities, such as ventricular enlargement, grey matter loss in the hippocampus and cerebellum, volume decreases in the prefrontal cortex and variations in the size of the amygdala. Other studies demonstrated that serum concentrations of neurotrophic factors, inflammatory mediators and oxidative stress may be used as BD biomarkers. Conclusions: The analysis of neurobiological changes associated with BD progression and activity may confirm the existence of BD biomarkers, which may be then included in staging models that will lead to improvements in treatment algorithms and more effective, individually tailored treatment regimens. Biomarkers may also be used to define early interventions to control disease progression.Introdução: Níveis crescentes de evidência sugerem que o transtorno bipolar (TB) exibe um caráter progressivo, em nível tanto clínico, quanto bioquímico e neuroimagiológico. Este estudo revisa a literatura existente sobre a relação entre biomarcadores específicos e estágios do TB. Métodos: Uma busca extensa da literatura nas bases de dados MEDLINE e PubMed foi conduzida para identificar estudos publicados em inglês e em português utilizando as palavraschave biomarker (biomarcador), neurotrophic factors (fatores neurotróficos), inflammation (inflamação), oxidative stress (estresse oxidativo), neuroprogression (neuroprogressão) e staging models (modelos de estadiamento), em referência cruzada com o termo bipolar disorder (transtorno bipolar). Resultados: Estudos morfométricos em doentes bipolares mostraram a existência de alterações neuroanatômicas, tais como o alargamento dos ventrículos, a perda de substância cinzenta no hipocampo e no cerebelo, a diminuição do volume de determinadas áreas do córtex pré-frontal e variações no tamanho da amígdala. Além disso, outros estudos apontam para a potencialidade do uso dos valores séricos dos fatores neurotróficos, de mediadores inflamatórios e de estresse oxidativo como biomarcadores do TB. Conclusões: O conhecimento das alterações neurobiológicas, associadas à progressão e atividade do TB, é fundamental para a identificação de biomarcadores. A incorporação de biomarcadores nos modelos de estadiamento do TB poderá permitir um aperfeiçoamento dos algoritmos terapêuticos, possibilitando a elaboração de esquemas de tratamento mais personalizados e eficazes, com destaque para a importância da intervenção precoce na atenuação da progressão da doença