Brain glucose hypometabolism and hippocampal inflammation in Goto-Kakizaki rats

Author(s):Show less -

J.C.O. Borges ^[1] ; V.A.B. Oliveira ^[2] ; T.D.A. Serdan ^[3] ; F.L.R. Silva ^[4] ; C.S. Santos ^[5] ; J.R.B. Pauferro ^[6] ; A.S.F. Ribas ^[7] ; R. Manoel ^[8] ; A.C.G. Pereira ^[9] ; I.S. Correa ^[10] ; J.N.B. Pereira ^[11] ; R.B. Bazotte ^[12] ; A.C. Levada-Pires ^[13] ; T.C. Pithon-Curi ^[14] ; R. Gorjão ^[15] ; R. Curi ; S.M. Hirabara ^[17] ; L.N. Masi

Affiliation:Show less -

^[1] Universidade Cruzeiro do Sul. Programa Interdisciplinar de Ciências da Saúde - Brasil

^[2] Universidade Cruzeiro do Sul. Programa Interdisciplinar de Ciências da Saúde - Brasil

^[3] Universidade Cruzeiro do Sul. Programa Interdisciplinar de Ciências da Saúde - Brasil

^[4] Universidade Cruzeiro do Sul. Programa Interdisciplinar de Ciências da Saúde - Brasil

^[5] Universidade Cruzeiro do Sul. Programa Interdisciplinar de Ciências da Saúde - Brasil

^[6] Universidade Cruzeiro do Sul. Programa Interdisciplinar de Ciências da Saúde - Brasil

^[7] Universidade Cruzeiro do Sul. Programa Interdisciplinar de Ciências da Saúde - Brasil

^[8] Universidade Cruzeiro do Sul. Programa Interdisciplinar de Ciências da Saúde - Brasil

^[9] Universidade Cruzeiro do Sul. Programa Interdisciplinar de Ciências da Saúde - Brasil

^[10] Universidade Cruzeiro do Sul. Programa Interdisciplinar de Ciências da Saúde - Brasil

^[11] Instituto Butantan. Bioindustrial Centro. Seção de Produção de Imunobiológicos - Brasil

^[12] Universidade Estadual de Maringá. Departamento de Farmacologia e Terapêutica. Programa de Pós-Graduação em Ciências Farmacêuticas - Brasil

^[13] Universidade Cruzeiro do Sul. Programa Interdisciplinar de Ciências da Saúde - Brasil

^[14] Universidade Cruzeiro do Sul. Programa Interdisciplinar de Ciências da Saúde - Brasil

^[15] Universidade Cruzeiro do Sul. Programa Interdisciplinar de Ciências da Saúde - Brasil

^[17] Universidade Cruzeiro do Sul. Programa Interdisciplinar de Ciências da Saúde - Brasil

• Document type: Journal article
• Source: Brazilian Journal of Medical and Biological Research; v. 56, 2023-06-26.

Abstract

Brain glucose hypometabolism and neuroinflammation are early pathogenic manifestations in neurological disorders. Neuroinflammation may also disrupt leptin signaling, an adipokine that centrally regulates appetite and energy balance by acting on the hypothalamus and exerting neuroprotection in the hippocampus. The Goto-Kakizaki (GK) rat is a non-obese type 2 diabetes mellitus (T2DM) animal model used to investigate diabetes-associated molecular mechanisms without obesity jeopardizing effects. Wistar and GK rats received the maintenance adult rodent diet. Also, an additional control group of Wistar rats received a high-fat and high-sugar diet (HFHS) provided by free consumption of condensed milk. All diets and water were provided ad libitum for eight weeks. Brain glucose uptake was evaluated by 2-deoxy-2-[fluorine-18] fluoro-D-glucose under basal (saline administration) or stimulated (CL316,243, a selective β3-AR agonist) conditions. The animals were fasted for 10-12 h, anesthetized, and euthanized. The brain was quickly dissected, and the hippocampal area was sectioned and stored at -80°C in different tubes for protein and RNA analyses on the same animal. GK rats exhibited attenuated brain glucose uptake compared to Wistar animals and the HFHS group under basal conditions. Also, the hippocampus of GK rats displayed upregulated leptin receptor, IL-1β, and IL-6 gene expression and IL-1β and the subunit of the transcription factor NF-κB (p-p65) protein expression. No significant alterations were detected in the hippocampus of HFHS rats. Our data indicated that a genetic predisposition to T2DM has significant brain deteriorating features, including brain glucose hypometabolism, neuroinflammation, and leptin signaling disruption in the hippocampal area. (AU)

• FAPESP's process: 21/02829-9 - Liver metabolic response in spontaneous type 2 Diabetic goto-kakizaki rats transplanted with bone marrow stem cells
• Grantee: João Carlos de Oliveira Borges
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/09868-7 - Cellular and molecular mechanisms of insulin resistance and inflammation in obese Wistar rats and lean Goto-Kakizaki rats: causes and associations with diet and physical exercise
• Grantee: Rui Curi
• Support Opportunities: Research Projects - Thematic Grants