PMID- 33486357
OWN - NLM
STAT- MEDLINE
DCOM- 20211108
LR  - 20240226
IS  - 1558-1497 (Electronic)
IS  - 0197-4580 (Print)
IS  - 0197-4580 (Linking)
VI  - 100
DP  - 2021 Apr
TI  - Loss of NRF2 accelerates cognitive decline, exacerbates mitochondrial 
      dysfunction, and is required for the cognitive enhancing effects of Centella 
      asiatica during aging.
PG  - 48-58
LID - S0197-4580(20)30409-7 [pii]
LID - 10.1016/j.neurobiolaging.2020.11.019 [doi]
AB  - The water extract of Centella asiatica (CAW) improves cognitive and mitochondrial 
      function and activates the nuclear factor erythroid 2-related factor 2 (NRF2) 
      regulated antioxidant response pathway in aged mice. Here we investigate whether 
      NRF2 activation is required for the cognitive and mitochondrial effects of 
      prolonged CAW exposure during aging. Five-month-old NRF2 knockout (NRF2KO) and 
      wild-type mice were treated with CAW for 1, 7, or 13 months. Each cohort 
      underwent cognitive testing and hippocampal mitochondrial analyses. Age-related 
      cognitive decline was accelerated in NRF2KO mice and while CAW treatment improved 
      cognitive performance in wild-type mice, it had no effect on NRF2KO animals. 
      Hippocampal mitochondrial function also declined further with age in NRF2KO mice 
      and greater hippocampal mitochondrial dysfunction was associated with poorer 
      cognitive performance in both genotypes. Long-term CAW treatment did not affect 
      mitochondrial endpoints in animals of either genotype. These data indicate that 
      loss of NRF2 results in accelerated age-related cognitive decline and worsened 
      mitochondrial deficits. NRF2 also appears to be required for the cognitive 
      enhancing effects of CAW during aging.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Zweig, Jonathan A
AU  - Zweig JA
AD  - Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
FAU - Brandes, Mikah S
AU  - Brandes MS
AD  - Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
FAU - Brumbach, Barbara H
AU  - Brumbach BH
AD  - Biostatistics & Design Program, Oregon Health & Science University, Portland, OR, 
      USA.
FAU - Caruso, Maya
AU  - Caruso M
AD  - Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
FAU - Wright, Kirsten M
AU  - Wright KM
AD  - Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
FAU - Quinn, Joseph F
AU  - Quinn JF
AD  - Department of Neurology, Oregon Health & Science University, Portland, OR, USA; 
      Department of Neurology and Parkinson's Disease Research Education and Clinical 
      Care Center (PADRECC), VA Portland Healthcare System, Portland, OR, USA.
FAU - Soumyanath, Amala
AU  - Soumyanath A
AD  - Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
FAU - Gray, Nora E
AU  - Gray NE
AD  - Department of Neurology, Oregon Health & Science University, Portland, OR, USA. 
      Electronic address: grayn@ohsu.edu.
LA  - eng
GR  - R00 AT008831/AT/NCCIH NIH HHS/United States
GR  - R01 AT008099/AT/NCCIH NIH HHS/United States
GR  - T32 AT002688/AT/NCCIH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20201225
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (Antioxidants)
RN  - 0 (Centella asiatica extract)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 0 (Plant Extracts)
RN  - 0 (Triterpenes)
SB  - IM
MH  - Aging/drug effects/*genetics/*psychology
MH  - Animals
MH  - *Antioxidants
MH  - Centella
MH  - Cognition/*drug effects
MH  - Cognitive Dysfunction/drug therapy/*genetics/psychology
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mitochondria
MH  - Mitochondrial Diseases/drug therapy/*genetics/psychology
MH  - NF-E2-Related Factor 2/genetics/metabolism/*physiology
MH  - *Phytotherapy
MH  - Plant Extracts
MH  - Triterpenes/*pharmacology/therapeutic use
MH  - Mice
PMC - PMC7920997
MID - NIHMS1660529
OTO - NOTNLM
OT  - Aging
OT  - Cognitive impairment
OT  - Mitochondrial dysfunction
COIS- Disclosure statement The authors report no conflicts of interest. Declarations of 
      interest: none.
EDAT- 2021/01/25 06:00
MHDA- 2021/11/09 06:00
PMCR- 2022/04/01
CRDT- 2021/01/24 20:42
PHST- 2019/12/17 00:00 [received]
PHST- 2020/11/30 00:00 [revised]
PHST- 2020/11/30 00:00 [accepted]
PHST- 2021/01/25 06:00 [pubmed]
PHST- 2021/11/09 06:00 [medline]
PHST- 2021/01/24 20:42 [entrez]
PHST- 2022/04/01 00:00 [pmc-release]
AID - S0197-4580(20)30409-7 [pii]
AID - 10.1016/j.neurobiolaging.2020.11.019 [doi]
PST - ppublish
SO  - Neurobiol Aging. 2021 Apr;100:48-58. doi: 10.1016/j.neurobiolaging.2020.11.019. 
      Epub 2020 Dec 25.