PMID- 32754028
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1663-4365 (Print)
IS  - 1663-4365 (Electronic)
IS  - 1663-4365 (Linking)
VI  - 12
DP  - 2020
TI  - Zonisamide Ameliorates Cognitive Impairment by Inhibiting ER Stress in a Mouse 
      Model of Type 2 Diabetes Mellitus.
PG  - 192
LID - 10.3389/fnagi.2020.00192 [doi]
LID - 192
AB  - Type 2 diabetes mellitus (T2DM) increases the risk of Alzheimer's disease 
      (AD)-like dementia and pathology. Endoplasmic reticulum stress (ERS) plays a key 
      role in the development of cognitive impairment in T2DM. Zonisamide (ZNS) was 
      found to suppress ERS-induced neuronal cell damage in the experimental models of 
      Parkinson's disease (PD). However, the protective effect of Zonisamide in the 
      treatment of diabetes-related dementia is not determined. Here, we studied 
      whether ZNS can attenuate cognitive impairments in T2DM mice. C57BL/6J mice were 
      fed with a high-fat diet (HFD) and received one intraperitoneal injection of 
      streptozotocin (STZ) to develop T2DM. After the 9-week diet, the mice were orally 
      gavaged with ZNS or vehicle for 16 consecutive weeks. We found that ZNS improved 
      spatial learning and memory ability and slightly attenuated hyperglycemia. In 
      addition, the expression levels of synaptic-related proteins, such as 
      postsynaptic density 95 (PSD95) and synaptophysin, were increased along with the 
      activation of the cyclic AMP response element-binding (CREB) protein and 
      cAMP-dependent protein kinase (PKA) both in the hippocampus and cortex of T2DM 
      mice. Meanwhile, ZNS attenuated Abeta deposition, Tau hyperphosphorylation at 
      Ser-396/404, and also decreased the activity of Tau upstream kinases including 
      extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). 
      Moreover, ZNS also decreased the ERS hallmark protein levels. These data suggest 
      that ZNS can efficiently prevent cognitive impairment and improve AD-like 
      pathologies by attenuating ERS in T2DM mice.
CI  - Copyright (c) 2020 He, Shen, Tian, Wu, Xue, Zhang, Wei and Liu.
FAU - He, Yong-Xiang
AU  - He YX
AD  - Department of Pharmacology, Key Laboratory of Molecular Target & Clinical 
      Pharmacology, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, 
      Guangzhou Medical University, Guangzhou, China.
FAU - Shen, Qi-Ying
AU  - Shen QY
AD  - Department of Pharmacology, Key Laboratory of Molecular Target & Clinical 
      Pharmacology, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, 
      Guangzhou Medical University, Guangzhou, China.
FAU - Tian, Jia-Hui
AU  - Tian JH
AD  - Department of Pharmacology, Key Laboratory of Molecular Target & Clinical 
      Pharmacology, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, 
      Guangzhou Medical University, Guangzhou, China.
FAU - Wu, Qian
AU  - Wu Q
AD  - Department of Pharmacology, Key Laboratory of Molecular Target & Clinical 
      Pharmacology, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, 
      Guangzhou Medical University, Guangzhou, China.
FAU - Xue, Qin
AU  - Xue Q
AD  - Department of Pharmacology, Key Laboratory of Molecular Target & Clinical 
      Pharmacology, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, 
      Guangzhou Medical University, Guangzhou, China.
FAU - Zhang, Gui-Ping
AU  - Zhang GP
AD  - Department of Pharmacology, Key Laboratory of Molecular Target & Clinical 
      Pharmacology, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, 
      Guangzhou Medical University, Guangzhou, China.
FAU - Wei, Wei
AU  - Wei W
AD  - Department of Pathophysiology, School of Medicine, Institute of Brain Research, 
      Key Laboratory of State Administration of Traditional Chinese Medicine of China, 
      Jinan University, Guangzhou, China.
FAU - Liu, Ying-Hua
AU  - Liu YH
AD  - Department of Pharmacology, Key Laboratory of Molecular Target & Clinical 
      Pharmacology, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, 
      Guangzhou Medical University, Guangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20200709
PL  - Switzerland
TA  - Front Aging Neurosci
JT  - Frontiers in aging neuroscience
JID - 101525824
PMC - PMC7367218
OTO - NOTNLM
OT  - Abeta
OT  - ER stress
OT  - Tau
OT  - Zonisamide
OT  - cognitive impairment
OT  - type 2 diabetes mellitus
EDAT- 2020/08/06 06:00
MHDA- 2020/08/06 06:01
PMCR- 2020/01/01
CRDT- 2020/08/06 06:00
PHST- 2020/04/28 00:00 [received]
PHST- 2020/06/02 00:00 [accepted]
PHST- 2020/08/06 06:00 [entrez]
PHST- 2020/08/06 06:00 [pubmed]
PHST- 2020/08/06 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fnagi.2020.00192 [doi]
PST - epublish
SO  - Front Aging Neurosci. 2020 Jul 9;12:192. doi: 10.3389/fnagi.2020.00192. 
      eCollection 2020.