PMID- 36512295
OWN - NLM
STAT- MEDLINE
DCOM- 20230404
LR  - 20230414
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Linking)
VI  - 48
IP  - 5
DP  - 2023 May
TI  - Apelin-13 Improves Cognitive Impairment and Repairs Hippocampal Neuronal Damage 
      by Activating PGC-1alpha/PPARgamma Signaling.
PG  - 1504-1515
LID - 10.1007/s11064-022-03844-1 [doi]
AB  - Alzheimer's disease (AD) is a complex neurodegenerative disease that is prevalent 
      around the world. Both Apelin-13 and proliferator-activated receptor-gamma 
      (PPARgamma)/PPARgamma co-activator 1alpha (PGC-1alpha) are regarded as candidate targets for 
      treating AD. The investigation examined whether Apelin-13 exerts neuroprotective 
      effects via PGC-1alpha/PPARgamma signaling. In this study, Apelin-13 improved cognitive 
      deficits in AD mice, while SR-18,292 (a PGC-1alpha inhibitor) interfered with the 
      therapeutic effects of Apelin-13. Mechanistically, Apelin-13, PGC-1alpha and PPARgamma 
      were decreased in AD mice and oxygen-glucose deprivation (OGD)-induced neuronal 
      cells. Apelin-13 bound to PGC-1alpha and negatively regulated the expression of 
      PGC-1alpha and PPARgamma. In turn, PGC-1alpha accelerated the accumulation of Apelin-13 and 
      PPARgamma. Additionally, neuronal apoptosis was inhibited, and the abundance of 
      apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase 3) was induced. The 
      content of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide 
      dismutase (SOD) fluctuated. The level of inflammatory factors (interleukin-6, 
      IL-6, IL-10, tumor necrosis factor-alpha, TNF-alpha) was regulated. In short, Apelin-13 
      exerted anti-apoptosis, anti-oxidant stress and anti-inflammatory effects. 
      Interestingly, PGC-1alpha silencing promoted neuronal apoptosis, oxidant stress and 
      inflammation, and overexpression of PGC-1alpha exhibited the opposite. More 
      importantly, inhibition of PGC-1alpha attenuated Apelin-13-enhanced cognitive 
      impairment and neuronal damage. Therefore, our findings suggested that Apelin-13 
      exerted neuroprotective effects in part via the PGC-1alpha/PPARgamma pathway.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Chen, Bin
AU  - Chen B
AD  - Department of Neurology, the Second Affiliated Hospital of Hainan Medical 
      University, 570216, Haikou, China.
AD  - Hainan Medical University, 571199, Haikou, China.
AD  - Key Laboratory of Brain Science Research & Transformation In Tropical Environment 
      of Hainan Province, 571199, Haikou, China.
AD  - International Center for Aging and Cancer (ICAC), 571199, Haikou, China.
FAU - Wu, Jingwei
AU  - Wu J
AD  - Department of Radiology, the Second Affiliated Hospital of Hainan Medical 
      University, 570216, Haikou, China.
FAU - Hu, Sheng
AU  - Hu S
AD  - Department of Neurology, the Second Affiliated Hospital of Hainan Medical 
      University, 570216, Haikou, China.
AD  - Hainan Medical University, 571199, Haikou, China.
FAU - Liu, Qingli
AU  - Liu Q
AD  - Department of Neurology, the Second Affiliated Hospital of Hainan Medical 
      University, 570216, Haikou, China.
AD  - Hainan Medical University, 571199, Haikou, China.
FAU - Yang, Hui
AU  - Yang H
AD  - Department of Neurology, the Second Affiliated Hospital of Hainan Medical 
      University, 570216, Haikou, China.
AD  - Hainan Medical University, 571199, Haikou, China.
FAU - You, Yong
AU  - You Y
AD  - Department of Neurology, the Second Affiliated Hospital of Hainan Medical 
      University, 570216, Haikou, China. youyong@hainmc.edu.cn.
AD  - Hainan Medical University, 571199, Haikou, China. youyong@hainmc.edu.cn.
AD  - Key Laboratory of Brain Science Research & Transformation In Tropical Environment 
      of Hainan Province, 571199, Haikou, China. youyong@hainmc.edu.cn.
AD  - International Center for Aging and Cancer (ICAC), 571199, Haikou, China. 
      youyong@hainmc.edu.cn.
LA  - eng
GR  - ZDYF2022SHFZ066/Hainan research and development project/
GR  - 821MS0834/Hainan Natural Science Foundation Project/
PT  - Journal Article
DEP - 20221213
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (apelin-13 peptide)
RN  - 0 (PPAR gamma)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Carrier Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
SB  - IM
EIN - Neurochem Res. 2023 Jan 4;:. PMID: 36598662
MH  - Mice
MH  - Animals
MH  - PPAR gamma/metabolism
MH  - *Neurodegenerative Diseases
MH  - *Neuroprotective Agents/pharmacology/therapeutic use
MH  - Antioxidants
MH  - Carrier Proteins/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Hippocampus/metabolism
MH  - *Cognitive Dysfunction/drug therapy
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Apelin-13
OT  - PGC-1alpha/PPARgamma
OT  - cognitive dysfunction
OT  - neuronal damage
EDAT- 2022/12/14 06:00
MHDA- 2023/04/04 06:42
CRDT- 2022/12/13 11:23
PHST- 2022/09/20 00:00 [received]
PHST- 2022/12/07 00:00 [accepted]
PHST- 2022/11/30 00:00 [revised]
PHST- 2023/04/04 06:42 [medline]
PHST- 2022/12/14 06:00 [pubmed]
PHST- 2022/12/13 11:23 [entrez]
AID - 10.1007/s11064-022-03844-1 [pii]
AID - 10.1007/s11064-022-03844-1 [doi]
PST - ppublish
SO  - Neurochem Res. 2023 May;48(5):1504-1515. doi: 10.1007/s11064-022-03844-1. Epub 
      2022 Dec 13.