Overweight and obesity are defined as abnormal or excessive fat accumulation that may impair health and they, currently, are the main problems for human welfare. Even if two millions of people in the world are malnourished, overweight and obesity are linked to more deaths worldwide than underweight. The metabolic dysfunction, dyslipidemia and inflammation caused by obesity contribute to the development of a wide variety of disorders and effects on the nervous system. In the Central Nervous System (CNS), mild cognitive impairment can be attributed to obesity induced alterations in hippocampal structure and function in some patients. Caloric-dense diet induced obesity (DIO), provides a useful animal model sharing several common features with human obesity. DIO rats of 7 weeks of age are expose to high fat (45 %) diet ad libitum and after 5 weeks the obese phenotype starts to be develop. To clarify the possible relationships between obesity and nervous system changes, DIO rats were studied after 5 weeks and 17 weeks of hypercaloric diet compared to the control rats with not fat diet (Chow). Moreover the effects of tart cherries juice and seeds powder on brain and adipose tissue of DIO rats were evaluated. DIO rats were studied after 17 weeks under hypercaloric diet with the supplementation of tart cherries seeds powder (DS) or seeds powder plus tart cherries juice, containing 1mg of anthocyanins (DJS). To determine the systemic effects of high-caloric diet exposure, we examined food consumption, fat mass content and fasting glycaemia, insulin levels, cholesterol and triglycerides. Memory performance was measured using different cognitive tests. RT-PCR, western blot and morphological analysis were performed in brain and adipose tissue. After 17 weeks of fat diet, rats increased significantly their body weight in comparison to the CHOW rats. No differences in body weight were observed in DS and DJS rats compared to age matched DIO rats. Supplementation of tart cherries in DS and DJS decreased the blood pressure and the glycaemia. Furthermore, the serum levels of thiobarbituric reactive substances decreased. In the visceral adipose tissue, tart cherries were able to reduce inflammatory status. Behavioral tests such as open-field test revealed, in the older DIO rats, a decrease of cumulative distance traveled their number of rearing and increasing the total immobility time. DIO rats present also a decrease in the number of entries into the central zone and the time spent by the animals in this area of the field compared the age-matched CHOW rats. In DIO rats a significant decrease of the ratio between time in zone 1 and central zone was observed. This indicates a condition of anxiety not mediated by an increase of immobility time. Only older DIO rats showed a reduction of retention latency time in the emotional learning task compared to the CHOW rats. Contemporaneous administration of seed powder and tart cherry juice not modified alteration in behavioral learning task. Immunohistochemical and immunochemical analysis showed an increased expression of glial fibrillary acid protein in the frontal cortex and hippocampus of older DIO rats compared to age matched CHOW. A decrease of Neurofilament expression was found in the hippocampus of 17 week-old DIO rats. The increase of GFAP-immunoreactive astrocytes, points out a suffering nervous tissue in a condition of hyperglycemia and hypertension, and/or a tendency of astrocytes to protect neuronal microenvironment. These morphological changes can be correlated to significant cerebrovascular and neuronal alterations in the DIO rat and could explain the behavioral results and the alteration of the learning tasks. In the brain of rats supplemented with tart cherries fruits, a reduction of both glial-fibrillary acid protein immunoreaction and a microglial activation decreasing was found. Moreover, there is an increase of Neurofilament expression in treated rats compared to DIO. Nevertheless, tart cherries are able to modify the modulation of synaptic proteins and ions channels expression in DIO rats. The characterization of morphological alterations in DIO rats brain, represent the first step to explain the neurodegenerative phenomena in the human brain of obese subjects. Several investigations have suggested that obesity and Mets may be linked to the risk of developing cognitive decline and Vascular Dementia (VaD). However vascular risk factors, developed in the obese subjects taken separately such as hypertension, dyslipidemia, and diabetes have been shown to play an important role in the development of Mild Cognitive Impairment (MCI), dementia, and Alzheimer’s disease (AD). The positive effects of tart cherries suggest that supplementation, although it did not affect the body weight in DIO rats, is able to prevent the obesity induced end-organ damage. Further studies are needed to better clarify the benefits of tart cherry treatment on disease prevention and health status maintenance. In fact a supplementation with tart cherries fruit, a rich source of anthocyanins, could be propose as a possible nutritional approach with protective effects on brain and adipose tissue.
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|Titolo:||Obesity-related Nervous System Injury: effects of Tart Cherries (Prunus Cerasus L.) supplementation in rats with Diet induced Obesity|
|Data di pubblicazione:||27-feb-2019|
|Appare nelle tipologie:||Tesi di dottorato|