Apomorphine Therapy for Neuronal Insulin Resistance in a Mouse Model of Alzheimer's Disease

Norimichi Nakamura, Yasumasa Ohyagi, Tomohiro Imamura, Yuki T. Yanagihara, Kyoko M. Iinuma, Naoko Soejima, Hiroyuki Murai, Ryo Yamasaki, Jun-Ichi Kira

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Apomorphine (APO) promotes intraneuronal amyloid-β (Aβ) degradation and improves memory function in an Alzheimer's disease (AD) model, 3xTg-AD mice. Since insulin resistance is increased in AD neurons, we investigated the effects of APO on brain insulin resistance in 3xTg-AD mice at early and late stages. After 1-month subcutaneous injection of Apokyn® to 3xTg-AD mice at 6 or 12 months of age, memory function was significantly improved in both age groups. Protein levels of insulin-degrading enzyme (IDE), which is linked to insulin signaling and degrades Aβ, significantly increased in the 3xTg-AD mice brain compared with non-transgenic mice, and were further increased by APO. Protein levels of two types of serine-phosphorylated insulin receptor substrate-1 (IRS-1), pS616 and pS636/639, significantly decreased following APO treatment in the 13-month-old 3xTg-AD mice brain, suggesting improved brain insulin resistance. Immunostaining of the IDE, pS616 and pS636/639 IRS-1 demonstrated similar changes due to APO treatment. Thus, brain insulin resistance is considered an important therapeutic target in AD, and APO may provide improved neuronal insulin resistance.

Original languageEnglish
Pages (from-to)1151-1161
Number of pages11
JournalJournal of Alzheimer's Disease
Volume58
Issue number4
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Apomorphine
Insulin Resistance
Alzheimer Disease
Insulysin
Brain
Insulin Receptor Substrate Proteins
Therapeutics
Subcutaneous Injections
Amyloid
Serine
Proteins
Age Groups
Insulin
Neurons

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Nakamura, N., Ohyagi, Y., Imamura, T., Yanagihara, Y. T., Iinuma, K. M., Soejima, N., ... Kira, J-I. (2017). Apomorphine Therapy for Neuronal Insulin Resistance in a Mouse Model of Alzheimer's Disease. Journal of Alzheimer's Disease, 58(4), 1151-1161. https://doi.org/10.3233/JAD-160344

Apomorphine Therapy for Neuronal Insulin Resistance in a Mouse Model of Alzheimer's Disease. / Nakamura, Norimichi; Ohyagi, Yasumasa; Imamura, Tomohiro; Yanagihara, Yuki T.; Iinuma, Kyoko M.; Soejima, Naoko; Murai, Hiroyuki; Yamasaki, Ryo; Kira, Jun-Ichi.

In: Journal of Alzheimer's Disease, Vol. 58, No. 4, 01.01.2017, p. 1151-1161.

Research output: Contribution to journalArticle

Nakamura, N, Ohyagi, Y, Imamura, T, Yanagihara, YT, Iinuma, KM, Soejima, N, Murai, H, Yamasaki, R & Kira, J-I 2017, 'Apomorphine Therapy for Neuronal Insulin Resistance in a Mouse Model of Alzheimer's Disease', Journal of Alzheimer's Disease, vol. 58, no. 4, pp. 1151-1161. https://doi.org/10.3233/JAD-160344
Nakamura N, Ohyagi Y, Imamura T, Yanagihara YT, Iinuma KM, Soejima N et al. Apomorphine Therapy for Neuronal Insulin Resistance in a Mouse Model of Alzheimer's Disease. Journal of Alzheimer's Disease. 2017 Jan 1;58(4):1151-1161. https://doi.org/10.3233/JAD-160344
Nakamura, Norimichi ; Ohyagi, Yasumasa ; Imamura, Tomohiro ; Yanagihara, Yuki T. ; Iinuma, Kyoko M. ; Soejima, Naoko ; Murai, Hiroyuki ; Yamasaki, Ryo ; Kira, Jun-Ichi. / Apomorphine Therapy for Neuronal Insulin Resistance in a Mouse Model of Alzheimer's Disease. In: Journal of Alzheimer's Disease. 2017 ; Vol. 58, No. 4. pp. 1151-1161.
@article{836b1cd5574b493bbdf9057ff11fe1e8,
title = "Apomorphine Therapy for Neuronal Insulin Resistance in a Mouse Model of Alzheimer's Disease",
abstract = "Apomorphine (APO) promotes intraneuronal amyloid-β (Aβ) degradation and improves memory function in an Alzheimer's disease (AD) model, 3xTg-AD mice. Since insulin resistance is increased in AD neurons, we investigated the effects of APO on brain insulin resistance in 3xTg-AD mice at early and late stages. After 1-month subcutaneous injection of Apokyn{\circledR} to 3xTg-AD mice at 6 or 12 months of age, memory function was significantly improved in both age groups. Protein levels of insulin-degrading enzyme (IDE), which is linked to insulin signaling and degrades Aβ, significantly increased in the 3xTg-AD mice brain compared with non-transgenic mice, and were further increased by APO. Protein levels of two types of serine-phosphorylated insulin receptor substrate-1 (IRS-1), pS616 and pS636/639, significantly decreased following APO treatment in the 13-month-old 3xTg-AD mice brain, suggesting improved brain insulin resistance. Immunostaining of the IDE, pS616 and pS636/639 IRS-1 demonstrated similar changes due to APO treatment. Thus, brain insulin resistance is considered an important therapeutic target in AD, and APO may provide improved neuronal insulin resistance.",
author = "Norimichi Nakamura and Yasumasa Ohyagi and Tomohiro Imamura and Yanagihara, {Yuki T.} and Iinuma, {Kyoko M.} and Naoko Soejima and Hiroyuki Murai and Ryo Yamasaki and Jun-Ichi Kira",
year = "2017",
month = "1",
day = "1",
doi = "10.3233/JAD-160344",
language = "English",
volume = "58",
pages = "1151--1161",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "4",

}

TY - JOUR

T1 - Apomorphine Therapy for Neuronal Insulin Resistance in a Mouse Model of Alzheimer's Disease

AU - Nakamura, Norimichi

AU - Ohyagi, Yasumasa

AU - Imamura, Tomohiro

AU - Yanagihara, Yuki T.

AU - Iinuma, Kyoko M.

AU - Soejima, Naoko

AU - Murai, Hiroyuki

AU - Yamasaki, Ryo

AU - Kira, Jun-Ichi

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Apomorphine (APO) promotes intraneuronal amyloid-β (Aβ) degradation and improves memory function in an Alzheimer's disease (AD) model, 3xTg-AD mice. Since insulin resistance is increased in AD neurons, we investigated the effects of APO on brain insulin resistance in 3xTg-AD mice at early and late stages. After 1-month subcutaneous injection of Apokyn® to 3xTg-AD mice at 6 or 12 months of age, memory function was significantly improved in both age groups. Protein levels of insulin-degrading enzyme (IDE), which is linked to insulin signaling and degrades Aβ, significantly increased in the 3xTg-AD mice brain compared with non-transgenic mice, and were further increased by APO. Protein levels of two types of serine-phosphorylated insulin receptor substrate-1 (IRS-1), pS616 and pS636/639, significantly decreased following APO treatment in the 13-month-old 3xTg-AD mice brain, suggesting improved brain insulin resistance. Immunostaining of the IDE, pS616 and pS636/639 IRS-1 demonstrated similar changes due to APO treatment. Thus, brain insulin resistance is considered an important therapeutic target in AD, and APO may provide improved neuronal insulin resistance.

AB - Apomorphine (APO) promotes intraneuronal amyloid-β (Aβ) degradation and improves memory function in an Alzheimer's disease (AD) model, 3xTg-AD mice. Since insulin resistance is increased in AD neurons, we investigated the effects of APO on brain insulin resistance in 3xTg-AD mice at early and late stages. After 1-month subcutaneous injection of Apokyn® to 3xTg-AD mice at 6 or 12 months of age, memory function was significantly improved in both age groups. Protein levels of insulin-degrading enzyme (IDE), which is linked to insulin signaling and degrades Aβ, significantly increased in the 3xTg-AD mice brain compared with non-transgenic mice, and were further increased by APO. Protein levels of two types of serine-phosphorylated insulin receptor substrate-1 (IRS-1), pS616 and pS636/639, significantly decreased following APO treatment in the 13-month-old 3xTg-AD mice brain, suggesting improved brain insulin resistance. Immunostaining of the IDE, pS616 and pS636/639 IRS-1 demonstrated similar changes due to APO treatment. Thus, brain insulin resistance is considered an important therapeutic target in AD, and APO may provide improved neuronal insulin resistance.

UR - http://www.scopus.com/inward/record.url?scp=85021278392&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021278392&partnerID=8YFLogxK

U2 - 10.3233/JAD-160344

DO - 10.3233/JAD-160344

M3 - Article

VL - 58

SP - 1151

EP - 1161

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 4

ER -