TY - JOUR

T1 - Neuropeptide Y system mRNA expression changes in the hippocampus of a type I diabetes rat model

AU - Campos, Elisa J.

AU - Martins, João

AU - Brudzewsky, Dan

AU - Woldbye, David P. D.

AU - Ambrósio, António F.

PY - 2020

Y1 - 2020

N2 - Background: Neuropeptide Y (NPY) plays a crucial role in many neurobiological functions, such as cognition and memory. Cognitive and memory impairment have been described in diabetic patients. The metabolism of NPY is determined by the activity of proteases, primarily dipeptidyl-peptidase-IV (DPP-IV). Therefore, DPP-IV inhibitors, such as sitagliptin, may modulate the function of NPY. In this study, we investigated the effect of type 1 diabetes and sitagliptin treatment on the regulation of the mRNA encoding for NPY and its receptors (Y1, Y2, and Y5 receptors) in the hippocampus. Methods: Type 1 diabetes was induced in male Wistar rats by i.p. injection of streptozotocin. Starting two weeks after diabetes onset, animals were treated orally with sitagliptin (5 mg/kg, daily) for two weeks. The mRNA expression of Npy and its receptors (Npy1r, Npy2r, and Npy5r) in the hippocampus was evaluated using in situ hybridization with 33P-labeled oligonucleotides. Results: The mRNA expression of Npy, Npy1r and Npy5r was higher in the dentate gyrus, whereas Npy2r highest level was observed in the CA3 subregion. The mRNA expression of Npy, Npy1r and Npy5r in dentate gyrus, CA1 and CA3 was not affected by diabetes and/or by sitagliptin treatment. Type 1 diabetes increased the mRNA expression of Npy2r in the CA3 subregion, which was prevented by sitagliptin treatment. Conclusions: Our results show that type 1 diabetes, at early stages, induces mild changes in the NPY system in the hippocampus that were counteracted by sitagliptin treatment.

AB - Background: Neuropeptide Y (NPY) plays a crucial role in many neurobiological functions, such as cognition and memory. Cognitive and memory impairment have been described in diabetic patients. The metabolism of NPY is determined by the activity of proteases, primarily dipeptidyl-peptidase-IV (DPP-IV). Therefore, DPP-IV inhibitors, such as sitagliptin, may modulate the function of NPY. In this study, we investigated the effect of type 1 diabetes and sitagliptin treatment on the regulation of the mRNA encoding for NPY and its receptors (Y1, Y2, and Y5 receptors) in the hippocampus. Methods: Type 1 diabetes was induced in male Wistar rats by i.p. injection of streptozotocin. Starting two weeks after diabetes onset, animals were treated orally with sitagliptin (5 mg/kg, daily) for two weeks. The mRNA expression of Npy and its receptors (Npy1r, Npy2r, and Npy5r) in the hippocampus was evaluated using in situ hybridization with 33P-labeled oligonucleotides. Results: The mRNA expression of Npy, Npy1r and Npy5r was higher in the dentate gyrus, whereas Npy2r highest level was observed in the CA3 subregion. The mRNA expression of Npy, Npy1r and Npy5r in dentate gyrus, CA1 and CA3 was not affected by diabetes and/or by sitagliptin treatment. Type 1 diabetes increased the mRNA expression of Npy2r in the CA3 subregion, which was prevented by sitagliptin treatment. Conclusions: Our results show that type 1 diabetes, at early stages, induces mild changes in the NPY system in the hippocampus that were counteracted by sitagliptin treatment.

KW - Hippocampus

KW - In situ hybridization

KW - Neuropeptide Y system

KW - Sitagliptin

KW - Type 1 diabetes

U2 - 10.1016/j.aanat.2019.151419

DO - 10.1016/j.aanat.2019.151419

M3 - Journal article

C2 - 31563570

AN - SCOPUS:85072846622

VL - 227

JO - Annals of Anatomy

JF - Annals of Anatomy

SN - 0940-9602

M1 - 151419

ER -