PMID- 35871353
OWN - NLM
STAT- MEDLINE
DCOM- 20220908
LR  - 20230328
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Print)
IS  - 1387-2877 (Linking)
VI  - 89
IP  - 1
DP  - 2022
TI  - Reduced Hippocampal and Anterior Cingulate Expression of Antioxidant Enzymes and 
      Membrane Progesterone Receptors in Alzheimer's Disease with Depression.
PG  - 309-321
LID - 10.3233/JAD-220574 [doi]
AB  - BACKGROUND: Major depressive disorder (MDD) is a risk factor for dementia 
      including that caused by Alzheimer's disease (AD). Both MDD and AD have a higher 
      prevalence in women than men, and estrogen-related processes have been implicated 
      in this sex difference. OBJECTIVE: To identify if enhanced oxidative stress and 
      decreased expression of the memory enhancer insulin-like growth factor 2 (IGF2), 
      each implicated separately in MDD and AD, are exaggerated in individuals with 
      both AD and MDD compared to those with AD. METHODS: Expression of target genes 
      are determined by qPCR in postmortem hippocampus (Hip) and anterior cingulate 
      cortex (ACC) of individuals with dementia and autopsy confirmed AD and those of 
      AD+MDD. RESULTS: Transcript levels of the antioxidant enzymes catalase (CAT) and 
      superoxide dismutase 1 (SOD1), as well as IGF2 and its receptor (IGF2R) were 
      significantly lower in the Hip and ACC of individuals with both AD and MDD 
      compared to those with AD and no MDD. Expressions of Progestin and AdipoQ 
      Receptor Family Member 7 (PAQR7, alias progesterone receptor alpha, mPRa) and 
      PAQR8 (mPRbeta), receptors that bind neurosteroids, were also lower in the Hip and 
      ACC of AD+MDD samples compared to those of AD without MDD. Correlations among 
      these transcripts revealed that estrogen receptor 2 (ESR2) and mPR beta are direct 
      or indirect regulators of the expression of the antioxidant enzymes and IGF2R. 
      CONCLUSION: Reduced levels of antioxidant enzymes, decreased IGF2 expression, and 
      diminished estrogen or membrane progesterone receptor-dependent processes might 
      be more pronounced in the subpopulation of individuals with AD and MDD than 
      without MDD.
FAU - Luo, Wendy
AU  - Luo W
AD  - Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, 
      Northwestern University, Chicago, IL, USA.
FAU - Pryzbyl, Katherine J
AU  - Pryzbyl KJ
AD  - Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, 
      Northwestern University, Chicago, IL, USA.
FAU - Bigio, Eileen H
AU  - Bigio EH
AD  - Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School 
      of Medicine, Northwestern University, Chicago, IL, USA.
FAU - Weintraub, Sandra
AU  - Weintraub S
AD  - Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, 
      Northwestern University, Chicago, IL, USA.
AD  - Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School 
      of Medicine, Northwestern University, Chicago, IL, USA.
FAU - Mesulam, M-Marsel
AU  - Mesulam MM
AD  - Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School 
      of Medicine, Northwestern University, Chicago, IL, USA.
FAU - Redei, Eva E
AU  - Redei EE
AD  - Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, 
      Northwestern University, Chicago, IL, USA.
LA  - eng
GR  - P30 AG072977/AG/NIA NIH HHS/United States
GR  - R21 AG062968/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Antioxidants)
RN  - 0 (Estrogens)
RN  - 0 (PAQR7 protein, human)
RN  - 0 (Receptors, Progesterone)
RN  - 4G7DS2Q64Y (Progesterone)
SB  - IM
MH  - *Alzheimer Disease/genetics/metabolism
MH  - Antioxidants/metabolism
MH  - Depression
MH  - *Depressive Disorder, Major/genetics
MH  - Estrogens
MH  - Female
MH  - Gyrus Cinguli/metabolism
MH  - Hippocampus/metabolism
MH  - Humans
MH  - Male
MH  - Progesterone/metabolism
MH  - Receptors, Progesterone/genetics/metabolism
PMC - PMC10041688
MID - NIHMS1875875
OTO - NOTNLM
OT  - Antioxidant enzymes
OT  - depression
OT  - insulin like growth factor 2
OT  - membrane progesterone receptor
OT  - molecular vulnerability
OT  - sex/gender differences
COIS- CONFLICT OF INTEREST The authors have no conflict of interest to report.
EDAT- 2022/07/25 06:00
MHDA- 2022/09/09 06:00
PMCR- 2023/03/27
CRDT- 2022/07/24 10:01
PHST- 2022/07/25 06:00 [pubmed]
PHST- 2022/09/09 06:00 [medline]
PHST- 2022/07/24 10:01 [entrez]
PHST- 2023/03/27 00:00 [pmc-release]
AID - JAD220574 [pii]
AID - 10.3233/JAD-220574 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2022;89(1):309-321. doi: 10.3233/JAD-220574.