Hippocampal Endoplasmic Reticulum Stress Hastens Motor and Cognitive Decline in Adult Male Rats Sustainedly Exposed to High-Sucrose Diet
Bruno Araújo Serra Pinto,
Thamys Marinho Melo,
Karla Frida Torres Flister,
Lucas Martins França,
Vanessa Ribeiro Moreira,
Daniela Kajihara,
Nelmar Oliveira Mendes,
Silma Regina Pereira,
Francisco Rafael Martins Laurindo,
Antonio Marcus Andrade Paes
Affiliations
Bruno Araújo Serra Pinto
Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, Av. dos Portugueses 1966, Bacanga, São Luís 65080-805, MA, Brazil
Thamys Marinho Melo
Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, Av. dos Portugueses 1966, Bacanga, São Luís 65080-805, MA, Brazil
Karla Frida Torres Flister
Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, Av. dos Portugueses 1966, Bacanga, São Luís 65080-805, MA, Brazil
Lucas Martins França
Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, Av. dos Portugueses 1966, Bacanga, São Luís 65080-805, MA, Brazil
Vanessa Ribeiro Moreira
Laboratory of Genetics and Molecular Biology, Department of Biology, Federal University of Maranhão, Av. dos Portugueses 1966, Bacanga, São Luís 65080-805, MA, Brazil
Daniela Kajihara
Laboratory of Vascular Biology, Heart Institute of the School of Medicine, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiiar, 44, Cerqueira César, São Paulo 05403-900, SP, Brazil
Nelmar Oliveira Mendes
Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, Av. dos Portugueses 1966, Bacanga, São Luís 65080-805, MA, Brazil
Silma Regina Pereira
Laboratory of Genetics and Molecular Biology, Department of Biology, Federal University of Maranhão, Av. dos Portugueses 1966, Bacanga, São Luís 65080-805, MA, Brazil
Francisco Rafael Martins Laurindo
Laboratory of Vascular Biology, Heart Institute of the School of Medicine, University of São Paulo, Av. Dr. Enéas Carvalho de Aguiiar, 44, Cerqueira César, São Paulo 05403-900, SP, Brazil
Antonio Marcus Andrade Paes
Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão, Av. dos Portugueses 1966, Bacanga, São Luís 65080-805, MA, Brazil
Metabolic dysfunctions, such as hyperglycemia and insulin resistance, have been associated to cognitive impairment and dementia regardless of advanced age, although the underlying mechanisms are still elusive. Thus, this study investigates the deleterious effects of metabolic syndrome (MetS) induced by long-term exposure to a high-sucrose diet on motor and cognitive functions of male adult rats and its relationship with hippocampal endoplasmic reticulum (ER) stress. Weaned Wistar male rats were fed a high-sucrose diet until adulthood (HSD; 6 months old) and compared to both age-matched (CTR; 6 months old) and middle-aged chow-fed rats (OLD; 20 months old). MetS development, serum redox profile, behavioral, motor, and cognitive functions, and hippocampal gene/protein expressions for ER stress pro-adaptive and pro-apoptotic pathways, as well as senescence markers were assessed. Prolonged exposure to HSD induced MetS hallmarked by body weight gain associated to central obesity, hypertriglyceridemia, insulin resistance, and oxidative stress. Furthermore, HSD rats showed motor and cognitive decline similar to that in OLD animals. Noteworthy, HSD rats presented marked hippocampal ER stress characterized by failure of pro-adaptive signaling and increased expression of Chop, p21, and Parp-1 cleavage, markers of cell death and aging. This panorama resembles that found in OLD rats. In toto, our data showed that early and sustained exposure to a high-sucrose diet induced MetS, which subsequently led to hippocampus homeostasis disruption and premature impairment of motor and cognitive functions in adult rats.
