Memory impairments and increased GFAP expression in hippocampal astrocytes following hypercaloric diet in rats.

Eduardo Fernandes Bondan,Carolina Vieira Cardoso,Rosemari Otton,Maria De Fátima Monteiro Martins

doi:10.1590/0004-282x20190091

Abstract

Hypothalamic inflammation and glial fibrillary acidic protein (GFAP) overexpression in astrocytes are well described in obese animals, as are some cognitive and memory deficits. As the hippocampus plays important roles in the consolidation of information, this investigation aimed to observe the memory function and the astrocyte expression of GFAP in the hippocampus of rats that received either a hypercaloric or a normocaloric diet. Adult male Wistar rats received a high-fat (cafeteria) or a standard diet for 60 days. On the 61st day, the rats were submitted to the novel object recognition (NOR) test at three and 24 hours after the first contact with objects, to assess short-term and long-term memory, respectively. Thereafter, the rats were euthanized and their brains were collected for GFAP immunohistochemical investigation in the hippocampus (CA1, CA2, CA3 areas) and hypothalamus (periventricular and arcuate nuclei). Astrocytic reactivity was assessed by morphometry. Different white adipose tissue depots and brown adipose tissue were weighed to calculate the adiposity index. The hypercaloric diet increased body weight gain, adiposity index, white adipose tissue weight (epididymal, subcutaneous and retroperitoneal) and brown adipose tissue weight. Rats fed with the hypercaloric diet showed short-term and long-term memory impairments in the NOR test, as well as increased GFAP expression in astrocytes from all analyzed hypothalamic and hippocampal areas. This astrogliosis suggests that the neuroinflammatory response also occurs in the hippocampus and may be involved in the memory losses observed in obese/overweight animals.

Highlights

It was shown that other central nervous system (CNS) areas presented the same type of astrocyte response, such as the parietal and frontal cortex, the corpus callosum, the nucleus accumbens, the pons and the molecular and granular layers of the cerebellum[13]. The aim of this investigation was to determine if a hypercaloric diet could induce memory impairment and if the hippocampus could present an astrocyte reaction similar to that observed in other rat brain areas, which could help elucidate the genesis of mnemonic losses in obesity
No significant difference was seen in the final body weight between the HD and ND groups, rats fed with the HD showed increased body weight gain; epididymal, subcutaneous, and retroperitoneal white adipose tissue; and brown adipose tissue; as well as an increased adiposity index (p < 0.05)
WAT: white adipose tissue; ND group: rats fed with normocaloric diet; HD group: rats fed with hypercaloric diet. a: statistically significant difference compared with the ND group. p < 0.05 (Student’s T test)

Summary

Introduction

The aim of this investigation was to determine if a hypercaloric (cafeteria) diet could induce memory impairment and if the hippocampus could present an astrocyte reaction similar to that observed in other rat brain areas, which could help elucidate the genesis of mnemonic losses in obesity. As for the GFAP astrocyte expression, rat brains from the HD group showed increased reactivity (p < 0.0001) in the arcuate and periventricular nuclei of the hypothalamus (Figure 2) as well as in the CA1, CA2 and CA3 areas of the hippocampus (Figure 3).

Results

Conclusion