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Effect of Angiotensin-(1-7) on nAChR and mGluR1 in Amygdala and Hippocampus and 8-arm Maze Performance of Rats in Aβ40-Induced Memory Impairment model
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  • Asli Erolan,
  • Zeynep Altunay,
  • Muhammed Doğan,
  • Funda BÖLÜKBAŞI HATIP,
  • Izzettin Hatip-Al-Khatib
Asli Erolan
Pamukkale University School of Medicine
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Zeynep Altunay
Pamukkale University, Health Sciences Institute-Neurosciences
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Muhammed Doğan
Pamukkale University School of Medicine
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Funda BÖLÜKBAŞI HATIP
Pamukkale University School of Medicine
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Izzettin Hatip-Al-Khatib
Pamukkale University School of Medicine

Corresponding Author:[email protected]

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Abstract

Background and Purpose Alzheimer’s disease (AD) is characterized by deposition of Amyloid-β-peptide (Aβ) plaques, memory impairment and dysfunction of renin-angiotensin system: the regulator arm is decreased whereas the classic Ang-II/III arm is elevated. This study aimed to investigate effect of Ang-(-7) on Aβ40-impaired memory and change of nAChR and mGluR1 sub units in amygdala(AMG) and hippocampus (HC). Experimental Approach In this study, AD model was induced by bilateral intra-amygdaloid injection of 3 nmol/3 µL amyloid beta peptide (Aβ40). Angiotensin (Ang)-(1-7) was injected ICV at 11.1 nmol/0.25 µL/h for 7 days. Memory was evaluated by measuring latency, correct (CC) and error choice (EC) in 8-arm radial maze (RAM) test. The expression of α7, α4 and β2 subunits of the nicotinic receptor (nAChR) and the metabotropic glutamate receptors (mGluR1) group subunits (mGluR1 and mGluR5) in AMG) and HC were analyzed by Western-blotting method. Key Results Aβ40 and Ang-(1-7) displayed differential effects on nAChR, mGluR1 and mGluR5 and RAM. Aβ40 decreased CC, increased EC and prolonged the latency. Ang-(1-7) only decreased Aβ40-induced EC. In AMG, Aβ40 decreased α7, α4nAChR and mGluR5, but increased mGluR1. Ang-(1-7) decreased α7nAChR and mGluR5, but increased mGluR1, an effect increased by Aβ40. In HC, only Ang-(1-7) increased β2 nAChR, an effect decreased by Aβ40. Conclusion and Implications Aβ40 impaired RAM performance and decreased nAChR and mGluR5 especially in AMG but increased mGluR1 in both AMG and HC. Ang-(1-7) improved Aβ40-induced EC, increased β2 nAChR in HC, reversed the Aβ40-reduced α4 nAChR, and furthered Aβ40-increased mGluR1 in AMG.