Percepção de gestantes na Atenção Primária à Saúde sobre alimentação saudável / Perception of pregnant women in Primary Health Care about healthy eating

A gestação promove várias transformações no organismo feminino, levando a uma maior demanda energética e nutricional. Se a demanda não for alcançada, haverá uma competição entre o feto e a mãe, o que pode acarretar prejuízos ao desenvolvimento fetal. Embora amplamente discutida, não está muito claro como as gestantes enxergam a alimentação saudável e se conseguem segui-la no dia a dia. Nesse sentido, é importante saber como as gestantes compreendem o tema, se estão recebendo orientações, o que fazem com o saber adquirido e quais fatores estão influenciando suas escolhas alimentares. O objetivo da pesquisa foi verificar o conhecimento de gestantes atendidas na Atenção Primária à Saúde em Belém-PA sobre alimentação saudável, tal como caracterizar o perfil socioeconômico e demográfico e o estado nutricional das participantes. Trata-se de um estudo quanti-qualitativo realizado com 27 gestantes atendidas na UMS Guamá utilizando-se questionário com dados socioeconômicos e demográficos e formulário semiestruturado com perguntas acerca de sua percepção sobre alimentação saudável, além de peso, altura e idade gestacional declarados. Os dados qualitativos foram analisados pelos métodos Análise da Similitude e Nuvem de Palavras. O estudo apontou que a maioria das gestantes são jovens, possuem o ensino médio, são solteiras, tem renda de um salário mínimo e sabem como alcançar uma alimentação saudável, todavia, diversos fatores influenciam suas escolhas alimentares, sendo determinantes e condicionantes da situação de alimentação, nutrição e saúde, e do acesso e consumo de alimentos saudáveis no dia a dia. Em relação ao estado nutricional, observou-se o mesmo percentual de gestantes eutróficas e com excesso de peso, o que pode estar relacionado aos diversos fatores que influenciam suas escolhas alimentares.

Pregnancy promotes several transformations in the female organism, leading to a greater energetic and nutritional demand. If the demand is not met, there will be a competition between the fetus and the mother, which can cause harm to fetal development. Although widely discussed, it is not very clear how pregnant women see healthy eating and whether they can follow it during their daily life. Therefore, it is important to know how pregnant women understand this theme, whether they are receiving guidance, what they do with the acquired knowledge, and what factors are influencing their dietary choices. The aim of this study was to verify the knowledge of pregnant women assisted in primary health care in Belém, PA concerning healthy eating, such as characterizing the socioeconomic and demographic profile and nutritional status of the participants. This is a quantitative-qualitative study conducted with 27 pregnant women enrolled at MHC Guamá using a questionnaire with socioeconomic and demographic data and a semi-structured form with questions about their perception of healthy eating and self-declared weight, height, and gestational age. Qualitative data were analyzed using the Similitude Analysis and Word Cloud methods. The study pointed out that most pregnant women are young, have a high school education, are single, have one minimum wage income, and know how to achieve a healthy diet. However, several factors influence their food choices such as the conditions of their food, nutrition, and health, and the access and consumption of healthy foods on a daily basis. Regarding nutritional status, the same percentage of eutrophic and overweight pregnant women was observed, which may be related to the various factors that influence their dietary choices.

BACE1 inhibition more effectively suppresses initiation than progression of ß-amyloid pathology.

BACE1 is the rate-limiting protease in the production of synaptotoxic ß-amyloid (Aß) species and hence one of the prime drug targets for potential therapy of Alzheimer's disease (AD). However, so far pharmacological BACE1 inhibition failed to rescue the cognitive decline in mild-to-moderate AD patients, which indicates that treatment at the symptomatic stage might be too late. In the current study, chronic in vivo two-photon microscopy was performed in a transgenic AD model to monitor the impact of pharmacological BACE1 inhibition on early ß-amyloid pathology. The longitudinal approach allowed to assess the kinetics of individual plaques and associated presynaptic pathology, before and throughout treatment. BACE1 inhibition could not halt but slow down progressive ß-amyloid deposition and associated synaptic pathology. Notably, the data revealed that the initial process of plaque formation, rather than the subsequent phase of gradual plaque growth, is most sensitive to BACE1 inhibition. This finding of particular susceptibility of plaque formation has profound implications to achieve optimal therapeutic efficacy for the prospective treatment of AD.

Glycation potentiates α-synuclein-associated neurodegeneration in synucleinopathies.

α-Synuclein misfolding and aggregation is a hallmark in Parkinson's disease and in several other neurodegenerative diseases known as synucleinopathies. The toxic properties of α-synuclein are conserved from yeast to man, but the precise underpinnings of the cellular pathologies associated are still elusive, complicating the development of effective therapeutic strategies. Combining molecular genetics with target-based approaches, we established that glycation, an unavoidable age-associated post-translational modification, enhanced α-synuclein toxicity in vitro and in vivo, in Drosophila and in mice. Glycation affected primarily the N-terminal region of α-synuclein, reducing membrane binding, impaired the clearance of α-synuclein, and promoted the accumulation of toxic oligomers that impaired neuronal synaptic transmission. Strikingly, using glycation inhibitors, we demonstrated that normal clearance of α-synuclein was re-established, aggregation was reduced, and motor phenotypes in Drosophila were alleviated. Altogether, our study demonstrates glycation constitutes a novel drug target that can be explored in synucleinopathies as well as in other neurodegenerative conditions.

Seeding and transgenic overexpression of alpha-synuclein triggers dendritic spine pathology in the neocortex.

Although misfolded and aggregated α-synuclein (α-syn) is recognized in the disease progression of synucleinopathies, its role in the impairment of cortical circuitries and synaptic plasticity remains incompletely understood. We investigated how α-synuclein accumulation affects synaptic plasticity in the mouse somatosensory cortex using two distinct approaches. Long-term in vivo imaging of apical dendrites was performed in mice overexpressing wild-type human α-synuclein. Additionally, intracranial injection of preformed α-synuclein fibrils was performed to induce cortical α-syn pathology. We find that α-synuclein overexpressing mice show decreased spine density and abnormalities in spine dynamics in an age-dependent manner. We also provide evidence for the detrimental effects of seeded α-synuclein aggregates on dendritic architecture. We observed spine loss as well as dystrophic deformation of dendritic shafts in layer V pyramidal neurons. Our results provide a link to the pathophysiology underlying dementia associated with synucleinopathies and may enable the evaluation of potential drug candidates on dendritic spine pathology in vivo.

High plasticity of axonal pathology in Alzheimer's disease mouse models.

Axonal dystrophies (AxDs) are swollen and tortuous neuronal processes that are associated with extracellular depositions of amyloid ß (Aß) and have been observed to contribute to synaptic alterations occurring in Alzheimer's disease. Understanding the temporal course of this axonal pathology is of high relevance to comprehend the progression of the disease over time. We performed a long-term in vivo study (up to 210 days of two-photon imaging) with two transgenic mouse models (dE9xGFP-M and APP-PS1xGFP-M). Interestingly, AxDs were formed only in a quarter of GFP-expressing axons near Aß-plaques, which indicates a selective vulnerability. AxDs, especially those reaching larger sizes, had long lifetimes and appeared as highly plastic structures with large variations in size and shape and axonal sprouting over time. In the case of the APP-PS1 mouse only, the formation of new long axonal segments in dystrophic axons (re-growth phenomenon) was observed. Moreover, new AxDs could appear at the same point of the axon where a previous AxD had been located before disappearance (re-formation phenomenon). In addition, we observed that most AxDs were formed and developed during the imaging period, and numerous AxDs had already disappeared by the end of this time. This work is the first in vivo study analyzing quantitatively the high plasticity of the axonal pathology around Aß plaques. We hypothesized that a therapeutically early prevention of Aß plaque formation or their growth might halt disease progression and promote functional axon regeneration and the recovery of neural circuits.

Ambient Glutamate Promotes Paroxysmal Hyperactivity in Cortical Pyramidal Neurons at Amyloid Plaques via Presynaptic mGluR1 Receptors.

Synaptic dysfunctions and altered neuronal activity play major role in the pathophysiology of Alzheimer's disease (AD), with underlying mechanisms largely unknown. We report that in the prefrontal cortex of amyloid precursor protein-presenilin 1 and APP23 AD mice, baseline activity of pyramidal cells is disrupted by episodes of paroxysmal hyperactivity. Induced by spontaneous EPSC bursts, these incidents are prevalent in neurons proximal to amyloid plaques and involve enhanced activity of glutamate with metabotropic effects. Abolition of EPSC bursts by tetrodotoxin and SERCA ATPase blockers thapsigargin or cyclopiasonic acid suggests their presynaptic origin and sensitized store-released calcium. Accordingly, the rate of EPSC bursts activated by single axon stimulation is enhanced. Aggravation of the hyperactivity by blockers of excitatory amino acid transporter (±)-HIP-A and DL-TBOA together with histochemical and ultrastructural evidence for enrichment of plaque-related dystrophies with synaptic vesicles and SNARE protein SNAP-25 infer the later as hot-spots for ectopic release of glutamate. Inhibition of EPSC bursts by I/II mGluR1 blocker MCPG or selective mGluR1 antagonist LY367385 implicate metabotropic glutamatergic effects in generation of paroxysmal bursts. These findings demonstrate for the first time that at amyloid plaques, enhanced activity of nonsynaptic glutamate can promote irregular EPSC bursts with hyperactivity of pyramidal cells via mGluR1 receptors.

Systematic comparison of the effects of alpha-synuclein mutations on its oligomerization and aggregation.

Aggregation of alpha-synuclein (ASYN) in Lewy bodies and Lewy neurites is the typical pathological hallmark of Parkinson's disease (PD) and other synucleinopathies. Furthermore, mutations in the gene encoding for ASYN are associated with familial and sporadic forms of PD, suggesting this protein plays a central role in the disease. However, the precise contribution of ASYN to neuronal dysfunction and death is unclear. There is intense debate about the nature of the toxic species of ASYN and little is known about the molecular determinants of oligomerization and aggregation of ASYN in the cell. In order to clarify the effects of different mutations on the propensity of ASYN to oligomerize and aggregate, we assembled a panel of 19 ASYN variants and compared their behaviour. We found that familial mutants linked to PD (A30P, E46K, H50Q, G51D and A53T) exhibited identical propensities to oligomerize in living cells, but had distinct abilities to form inclusions. While the A30P mutant reduced the percentage of cells with inclusions, the E46K mutant had the opposite effect. Interestingly, artificial proline mutants designed to interfere with the helical structure of the N-terminal domain, showed increased propensity to form oligomeric species rather than inclusions. Moreover, lysine substitution mutants increased oligomerization and altered the pattern of aggregation. Altogether, our data shed light into the molecular effects of ASYN mutations in a cellular context, and established a common ground for the study of genetic and pharmacological modulators of the aggregation process, opening new perspectives for therapeutic intervention in PD and other synucleinopathies.