PMID- 38092521
OWN - NLM
STAT- MEDLINE
DCOM- 20231228
LR  - 20240104
IS  - 1549-5477 (Electronic)
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 37
IP  - 21-24
DP  - 2023 Dec 26
TI  - The steroid hormone ADIOL promotes learning by reducing neural kynurenic acid 
      levels.
PG  - 998-1016
LID - 10.1101/gad.350745.123 [doi]
AB  - Reductions in brain kynurenic acid levels, a neuroinhibitory metabolite, improve 
      cognitive function in diverse organisms. Thus, modulation of kynurenic acid 
      levels is thought to have therapeutic potential in a range of brain disorders. 
      Here we report that the steroid 5-androstene 3beta, 17beta-diol (ADIOL) reduces 
      kynurenic acid levels and promotes associative learning in Caenorhabditis elegans 
      We identify the molecular mechanisms through which ADIOL links peripheral 
      metabolic pathways to neural mechanisms of learning capacity. Moreover, we show 
      that in aged animals, which normally experience rapid cognitive decline, ADIOL 
      improves learning capacity. The molecular mechanisms that underlie the 
      biosynthesis of ADIOL as well as those through which it promotes kynurenic acid 
      reduction are conserved in mammals. Thus, rather than a minor intermediate in the 
      production of sex steroids, ADIOL is an endogenous hormone that potently 
      regulates learning capacity by causing reductions in neural kynurenic acid 
      levels.
CI  - (c) 2023 Lemieux et al.; Published by Cold Spring Harbor Laboratory Press.
FAU - Lemieux, George A
AU  - Lemieux GA
AD  - Department of Physiology, University of California, San Francisco, San Francisco, 
      California 94143, USA.
FAU - Yoo, Shinja
AU  - Yoo S
AD  - Department of Physiology, University of California, San Francisco, San Francisco, 
      California 94143, USA.
FAU - Lin, Lin
AU  - Lin L
AD  - Department of Physiology, University of California, San Francisco, San Francisco, 
      California 94143, USA.
FAU - Vohra, Mihir
AU  - Vohra M
AD  - Department of Physiology, University of California, San Francisco, San Francisco, 
      California 94143, USA.
FAU - Ashrafi, Kaveh
AU  - Ashrafi K
AD  - Department of Physiology, University of California, San Francisco, San Francisco, 
      California 94143, USA kaveh.ashrafi@ucsf.edu.
LA  - eng
GR  - P40 OD010440/OD/NIH HHS/United States
GR  - R01 AG046400/AG/NIA NIH HHS/United States
GR  - RF1 AG068194/AG/NIA NIH HHS/United States
GR  - S10 OD026962/OD/NIH HHS/United States
PT  - Journal Article
DEP - 20231226
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - H030S2S85J (Kynurenic Acid)
RN  - 0 (Steroids)
RN  - 0 (Hormones)
SB  - IM
MH  - Animals
MH  - *Kynurenic Acid/pharmacology
MH  - *Steroids
MH  - Hormones
MH  - Mammals
PMC - PMC10760639
OTO - NOTNLM
OT  - 5-androstenediol
OT  - estrogen receptor beta
OT  - kynurenic acid
OT  - kynurenine pathway
OT  - nuclear hormone receptor
EDAT- 2023/12/14 00:42
MHDA- 2023/12/28 06:42
PMCR- 2023/11/01
CRDT- 2023/12/13 21:03
PHST- 2023/04/24 00:00 [received]
PHST- 2023/11/22 00:00 [accepted]
PHST- 2023/12/28 06:42 [medline]
PHST- 2023/12/14 00:42 [pubmed]
PHST- 2023/12/13 21:03 [entrez]
PHST- 2023/11/01 00:00 [pmc-release]
AID - gad.350745.123 [pii]
AID - 10.1101/gad.350745.123 [doi]
PST - epublish
SO  - Genes Dev. 2023 Dec 26;37(21-24):998-1016. doi: 10.1101/gad.350745.123.