Effects of maternal high fat diet on brain-derived neurotrophic factor (BDNF), inflammatory pathway proteins and biomarkers oxidative stress in hippocampus of adult offspring of mice

• Grant number: 18/10380-9
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): April 01, 2019
• Effective date (End): December 31, 2019
• Field of knowledge: Health Sciences - Nutrition - Malnutrition and Physiological Development
• Principal researcher: Cristiano Mendes da Silva
• Grantee: Paula dos Santos Gomez
• Home Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil

Abstract

The effects of maternal high-fat diet (HFD) on rodents demonstrated that adult offspring of dams that consumed HFD during pregnancy and suckling showed neurological disorders (Giriko et al, 2013, Mendes-da-Silva et al., 2014). Many studies have linked highly caloric diets with decreased contextual and spatial memory in experiments with mice (Valladolid-Acebes et al., 2011; Kosari et al., 2012). Probably the result from these memory changes can be induced by the dietary action on hippocampal synaptic plasticity (Molteni et al., 2002; Wu et al., 2004). However, although there are variable speculations regarding the mechanisms of the effects of hypercaloric diets on memory and the hippocampus, it is possible that HFD and obesity may induce cognitive deficits by neuronal inflammatory processes (Wang et al., 2016). HFD may result in a systemic increase of proinflammatory cytokines, such as interleukin 1² (IL-1²), interleukin 6 (IL-6) and tumor necrosis factor ± (TNF±), and also increase of the inflammatory pathway of nuclear factor ºB (NFºB), peripherally or in the brain (Wang et al., 2016). This proinflammatory profile appears to be a cause or consequence of obesity (Miller and Spencer, 2014). In addition, 6-week-old male mice (C57BL/6) exposed to HFD for ± 3 months exhibited downregulation of some neurotropic factors, such as: neuronal growth factor ² (NGF²) and brain derived neurotrophic factor (BDNF) (Wang et al., 2016). According to these authors, results that may provide potential clues to a therapeutic and preventive strategy of HFD-induced cognitive decline (Wang et al., 2016). BDNF is a neurotrophic protein with the function of promoting the survival, differentiation and proliferation of neural cells. Studies have also shown that BDNF is involved with long-term synapses (Panja and Bramham, 2014), depressive symptoms (Zhang et al., 2014), neurogenesis (Liu and Nusslock, 2018) and memory associated with the hippocampus (Bekinschtein, Cammarota and Medina, 2014). Furthermore, changes in hippocampal BDNF, spatial learning and working memory, assessed by the Morris Water Maze behavioral test (MWM), are showed by rodents exposed to HFD (Kanoski et al., 2007; Kim and Park, 2010; Noble et al., 2014). These possible behavioral and BDNF levels/expression changes may be correlated to inflammatory mechanisms and from oxidative stress in neural tissue. In this context, studies with rodents demonstrate that excessive consumption of HFD can promote hippocampal oxidative stress. Male mice exposed to HFD for 12 weeks had decrease in the antioxidant enzyme superoxide dismutase (SOD), increase in the marker of oxidative stress Malondialdehyde (MDA) in the hippocampus and deficits in spatial memory and learning behaviors evaluated in MWM (FangFang et al., 2016). Another recent study demonstrated that HFD consumption for 4 weeks increased levels of oxidized glutathione (GSSG), decreased levels of reduced glutathione (GSH) and the GSSG/GSH ratio and increased the levels of Thiobarbituric acid reactive substances (TBARS) in the rat hippocampus (Alzoubi et al, 2018). These evidences indicate that the consumption of HFD can induce increase in the levels of oxidative agents and decrease of antioxidant agents compromising cognitive functions related to the hippocampus. Thus, it is necessary to investigate the possible effects of high-fat diets during the gestation and lactation periods on the brain/cognitive development of the adult offspring, researching aspects related to the BDNF, oxidative stress and inflammatory pathway in the hippocampus. (AU)