JHU-083 selectively blocks glutaminase activity in brain CD11b
Animals
Behavior, Animal
/ drug effects
CD11b Antigen
Depression
/ etiology
Diazooxonorleucine
/ pharmacology
Disease Models, Animal
Glutaminase
/ drug effects
Hippocampus
/ drug effects
Inflammation
/ drug therapy
Male
Mice
Mice, Inbred C57BL
Prefrontal Cortex
/ drug effects
Prodrugs
/ pharmacology
Signal Transduction
Stress, Psychological
/ complications
Journal
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
ISSN: 1740-634X
Titre abrégé: Neuropsychopharmacology
Pays: England
ID NLM: 8904907
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
02
11
2017
accepted:
29
07
2018
revised:
25
07
2018
pubmed:
22
8
2018
medline:
18
12
2019
entrez:
22
8
2018
Statut:
ppublish
Résumé
There are a number of clinically effective treatments for stress-associated psychiatric diseases, including major depressive disorder (MDD). Nonetheless, many patients exhibit resistance to first-line interventions calling for novel interventions based on pathological mechanisms. Accumulating evidence implicates altered glutamate signaling in MDD pathophysiology, suggesting that modulation of glutamate signaling cascades may offer novel therapeutic potential. Here we report that JHU-083, our recently developed prodrug of the glutaminase inhibitor 6-diazo-5-oxo-L-norleucine (DON) ameliorates social avoidance and anhedonia-like behaviors in mice subjected to chronic social defeat stress (CSDS). JHU-083 normalized CSDS-induced increases in glutaminase activity specifically in microglia-enriched CD11b
Identifiants
pubmed: 30127344
doi: 10.1038/s41386-018-0177-7
pii: 10.1038/s41386-018-0177-7
pmc: PMC6372721
doi:
Substances chimiques
CD11b Antigen
0
Itgam protein, mouse
0
Prodrugs
0
Diazooxonorleucine
03J0H273KZ
Glutaminase
EC 3.5.1.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
683-694Subventions
Organisme : NIMH NIH HHS
ID : P30 MH075673
Pays : United States
Organisme : NCCIH NIH HHS
ID : R21 AT008547
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH110246
Pays : United States
Organisme : NIMH NIH HHS
ID : R25 MH080661
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA041208
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH094268
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA193895
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA229451
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB028239
Pays : United States
Commentaires et corrections
Type : ErratumIn
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