Confirmation of Aβ1–42 oligomerization. Figure S2. Inhibition of PKR restores basal synaptic dysregulation in 5XFAD mice. Figure S3. ICR mice showed the low standard of the freezing behavior in contextual fear conditioning. Figure S4. Neither Aβ1–42 nor PKRi affected basal synaptic transmission and short-term synaptic plasticity. Figure S5. High frequency stimulation (HFS)-induced LTP is normal in 5XFAD mice. (DOCX 709 kb

Kyoung-Doo Hwang (4681849)

Myeong Bak (4681846)

Sang Kim (2421394)

Sangmyung Rhee (495319)

Yong-Seok Lee (83975)

Molecular Brain

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Additional file 1: Figure S1. of Restoring synaptic plasticity and memory in mouse models of Alzheimer’s disease by PKR inhibition

Abstract
              Alzheimers disease (AD) is a neurodegenerative disorder associated with deficits in cognition and synaptic plasticity. While accumulation of amyloid β (Aβ) and hyper-phosphorylation of tau are parts of the etiology, AD can be caused by a large number of different genetic mutations and other unknown factors. Considering such a heterogeneous nature of AD, it would be desirable to develop treatment strategies that can improve memory irrespective of the individual causes. Reducing the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) was shown to enhance long-term memory and synaptic plasticity in naïve mice. Moreover, hyper-phosphorylation of eIF2α is observed in the brains of postmortem AD patients. Therefore, regulating eIF2α phosphorylation can be a plausible candidate for restoring memory in AD by targeting memory-enhancing mechanism. In this study, we examined whether PKR inhibition can rescue synaptic and learning deficits in two different AD mouse models; 5XFAD transgenic and Aβ1–42-injected mice. We found that the acute treatment of PKR inhibitor (PKRi) can restore the deficits in long-term memory and long-term potentiation (LTP) in both mouse models without affecting the Aβ load in the hippocampus. Our results prove the principle that targeting memory enhancing mechanisms can be a valid candidate for developing AD treatment.This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C-1922- 010014) to Y.-S.L. K.-D.H. was supported by Graduate Research Scholarship from Chung-Ang University in 2015

Hwang, Kyoung-Doo

Bak, Myeong Seong

Kim, Sang Jeong

Rhee, Sangmyung

Lee, Yong-Seok

SNU Open Repository and Archive

Restoring synaptic plasticity and memory in mouse models of Alzheimers disease by PKR inhibition

Abstract Alzheimer’s disease (AD) is a neurodegenerative disorder associated with deficits in cognition and synaptic plasticity. While accumulation of amyloid β (Aβ) and hyper-phosphorylation of tau are parts of the etiology, AD can be caused by a large number of different genetic mutations and other unknown factors. Considering such a heterogeneous nature of AD, it would be desirable to develop treatment strategies that can improve memory irrespective of the individual causes. Reducing the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) was shown to enhance long-term memory and synaptic plasticity in naïve mice. Moreover, hyper-phosphorylation of eIF2α is observed in the brains of postmortem AD patients. Therefore, regulating eIF2α phosphorylation can be a plausible candidate for restoring memory in AD by targeting memory-enhancing mechanism. In this study, we examined whether PKR inhibition can rescue synaptic and learning deficits in two different AD mouse models; 5XFAD transgenic and Aβ1–42-injected mice. We found that the acute treatment of PKR inhibitor (PKRi) can restore the deficits in long-term memory and long-term potentiation (LTP) in both mouse models without affecting the Aβ load in the hippocampus. Our results prove the principle that targeting memory enhancing mechanisms can be a valid candidate for developing AD treatment

Kyoung-Doo Hwang

Myeong Seong Bak

Sang Jeong Kim

Sangmyung Rhee

Yong-Seok Lee

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Restoring synaptic plasticity and memory in mouse models of Alzheimer’s disease by PKR inhibition

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https://s-space.snu.ac.kr/bitstream/10371/138451/1/13041_2017_Article_338.pdf

Additional file 1: Figure S1. of Restoring synaptic plasticity and memory in mouse models of Alzheimer’s disease by PKR inhibition

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