Dieta rica em gordura induz alterações comportamentais em peixe-zebra adulto

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Patologia Molecular, 2021.A obesidade é uma doença de alta prevalência na população mundial (13% da população adulta em 2016), definida pelo acúmulo excessivo de gordura corporal. Várias comorbidades estão associadas, incluindo algumas que afetam o sistema nervoso central (SNC), como algumas doenças neurodegenerativas, o déficit cognitivo e distúrbios psicocomportamentais. O peixe-zebra surgiu como um modelo versátil e barato amplamente usado para estudar doenças humanas, incluindo obesidade e doenças neurológicas. Portanto, nosso objetivo foi verificar o impacto de uma dieta hiperlipídica no sistema nervoso central (SNC) do peixe-zebra, por meio de testes comportamentais bem estabelecidos. Os animais foram alimentados de acordo com três grupos dietéticos. O grupo de dieta padrão (SD) recebeu apenas 7,5 mg/ peixe de ração comercial para peixe, enquanto os grupos de dieta rica em gordura receberam 5 mg/peixe de ração + 7,5 (HFD- 7,5) ou 15 mg/ peixe (HFD-15) de gema de ovo de galinha. O teor de gordura dietética (p/p) foi de aproximadamente 6,5%, 16,9% e 21,1%, respectivamente. Após duas semanas de dieta, os comportamentos foram avaliados. Ambos os grupos HFD apresentaram efeitos obesogênicos, indicados pelo aumento no IMC, comprimento abdominal e peso corporal em comparação com o grupo SD. demonstramos um comportamento agressivo e tipo ansioso induzido por ingestão de HFD em peixes-zebra, conforme medido pelo teste de agressão induzida por espelho e teste de tanque novo, respectivamente. Além disso, a maior concentração de HFD (HFD-15) causou déficit cognitivo no teste de esquiva inibitória enquanto a sociabilidade não foi afetada, conforme determinado pelo teste de preferência social. Nossos resultados estão de acordo com evidências em modelos humanos e roedores obesos, sugerindo efeitos semelhantes da ingestão de gordura. Portanto, destacamos o potencial inexplorado do peixe-zebra para elucidar este campo de estudo.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).Obesity is a disease with high prevalence in the world population (13% of adult population in 2016), defined by an excessive body fat accumulation. Several comorbidities are associated, including some affecting central nervous system (CNS), i.e. some neurodegenerative diseases, the cognitive deficit and psychobehavioral disturbs. Zebrafish has raised as a versatile and cheap model widely used to study human diseases, including obesity and neurological diseases. Therefore, our objective was to verify the impact of a high-fat diet on zebrafish central nervous system (CNS) using well- stablished behavioral tests. Animals were feed according with three dietary groups. The standard diet group (SD) received only 7.5 mg/ fish of commercial fish food, while the high-fat diet groups received 5 mg/fish of commercial fish food + 7.5 (HFD-7.5) or 15 mg/fish (HFD-15) of chicken egg yolk. Dietary fat content (w/w) was approximately 6.5%, 16.9% and 21.1%, respectively. After two weeks of diets ingestion, behaviors were assessed. Both HFD groups had obesogenic effects, indicated by increase on BMI, abdominal length and body weight compared with SD group. We show a HFD ingestion induced aggressive and anxiety-like behavior on zebrafish, as measured by mirror-induced aggression and novel tank diving test, respectively. Also, the higher concentration of HFD (HFD-15) elicited cognitive deficit on inhibitory avoidance test while sociability was unaffected, as determined by the social preference test. Our results are in accordance with evidences in obese human and rodent models, suggesting similar effects of fat intake. Therefore, we highlight the unexplored potential of zebrafish to elucidate this study field

Potential neuroprotective and antiinfammatory efects provided by omega-3 (DHA) against Zika virus infection in human SH-SY5Y cells

Zika virus (ZIKV) has a strong tropism for the nervous system and has been related to post-infection neurological syndromes. Once neuronal cells are infected, the virus is capable of modulating cell metabolism, leading to neurotoxicity and cellular death. The negative efect of ZIKV in neuron cells has been characterized. However, the description of molecules capable of reversing these cytotoxic efects is still under investigation. In this context, it has been largely demonstrated that docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, is highly neuroprotective. Here, we hypothesized that DHA’s neuroprotective proprieties could have an infuence on ZIKV-induced neurotoxicity in SHSY5Y cells. Our data showed that pre-treatment of SH-SY5Y cells with DHA increased the cell viability and proliferation in ZIKV-infected cells. Moreover, DHA triggered an anti-infammatory response in those infected cells. Besides, DHA was capable of restoring mitochondria function and number in ZIKVinfected SH-SY5Y cells. In addition, cells pre-treated with DHA prior to ZIKV infection presented a lower viral load at diferent times of infection. Taking together, these results demonstrated that DHA has a potential anti-infammatory and neuroprotective efect against ZIKV infection in these neuron-like cells and could be a useful tool in the treatment against this virus

Metabolic activity in cryopreserved and grafted ovarian tissue using high-resolution respirometry

Cryopreservation of ovarian tissue followed by transplantation represents a strategy to restore ovarian function and fertility. Stress from cryopreservation-thawing processes can lead to alterations and/or damage to mitochondrial structure and functionality. High resolution respirometry and histological analysis were used to evaluate the effect of cryopreservation and transplantation on ovarian tissue. Four different conditions were performed: Fresh non-transplanted tissue, Fresh transplanted tissue, Cryopreserved non-transplanted tissue and Cryopreserved transplanted tissue. All groups were able to respond to the substrates-uncoupler-inhibitor protocol. We found a dramatic decrease in general oxygen consumption in hemi-ovaries submitted to cryopreservation and/or transplantation. The effect of cryopreservation on mitochondrial metabolism was less intense than effect of transplantation, since the transplantation affected all of the mitochondrial states. A total of 2644 follicles were analyzed. Of these, 2198 were classified as morphologically normal. The percentage of morphologically normal follicles was significantly lower in the Cryopreserved transplanted group when compared to the Cryopreserved non-transplanted group and the Fresh transplanted group (p-value < 0.05). Despite decreased follicular viability and mitochondrial activity, the cryopreservation followed by transplantation of ovarian tissue proved feasible for attempts to restore ovarian function

Early-life metabolic dysfunction impairs cognition and mitochondrial function in mice

The impact of overnutrition early in life is not restricted to the onset of cardiovascular and metabolic diseases, but also affects critical brain functions related to cognition. This study aimed to evaluate the relationship between peripheral metabolic and bioenergetic changes induced by a two-hit protocol and their impact on cognitive function in juvenile mice. Three-week-old male C57BL/6 mice received a high-fat diet (HFD) or control diet for 7 weeks, as sociated with two low doses of streptozotocin (STZ) or vehicle. Despite the absence of obesity, HFD+STZ impaired glucose metabolism and induced a trend towards cholesterol increase. The two-hit protocol impaired recognition and spatial memories in juvenile mice, without inducing a depressive-like behavior. HFD+STZ mice presented increased immunoreactivity for GFAP and a trend towards a decrease in NeuN in the hippocampus. The treatment caused a bioen ergetic impairment in the hippocampus, characterized by a decrease in both O2 consumption related to ATP production and in the maximum respiratory capacity. The thermogenic capacity of brown adipose tissue was impaired by the two-hit protocol, here verified through the absence of a decrease in O2 consumption after uncoupled protein-1 inhibition and an increase in the reserve respiratory capacity. Impaired mitochondrial function was also observed in the liver of HFD+STZ juvenile mice, but not in their heart. These results indicate that exposure to HFD+STZ early in life has a detrimental impact on the bioenergetic and mitochondrial function of tissues with metabolic and thermogenic activities, which is likely related to hippocampal metabolic changes and cognitive impairment.Instituto de Ciências Biológicas (IB)Departamento de Ciências Fisiológicas (IB CFS)Faculdade de Ciências da Saúde (FS)Departamento de Farmácia (FS FAR