D-Pinitol mitigates post-traumatic stress disorder-like behaviors induced by single prolonged stress in mice through mineralocorticoid receptor antagonism

Authors
Kong, Chang HyeonLee, Jin WooJeon, MijinKang, Woo ChangKim, Min SeoPark, KeontaeBae, Ho JungPark, Se JinJung, Seo YunKim, Su -NamKleinfelter, BenjaminKim, Ji-WoonRyu, Jong Hoon
Issue Date
2024-06
Publisher
Elsevier BV
Citation
Progress in Neuro-Psychopharmacology and Biological Psychiatry, v.132
Abstract
Post-traumatic stress disorder (PTSD) is a mental illness that can occur in individuals who have experienced trauma. Current treatments for PTSD, typically serotonin reuptake inhibitors, have limited effectiveness for patients and often cause serious adverse effects. Therefore, a novel class of treatment with better pharmacological profile is necessary. D-Pinitol has been reported to be effective for depression and anxiety disorders, but there are no reports associated with PTSD. In the present study, we investigated the effects of D-pinitol in a mouse model of PTSD induced by a single prolonged stress (SPS) protocol. We examined the therapeutic effects of D-pinitol on emotional and cognitive impairments in the SPS mouse model. We also investigated the effects of D-pinitol on fear memory formation. Mineralocorticoid receptor transactivation assay, Western blot, and quantitative PCR were employed to investigate how D-pinitol exerts its pharmacological activities. D-Pinitol ameliorated PTSD-like behaviors in a SPS mouse model. D-Pinitol also normalized the increased mRNA expression levels and protein levels of the mineralocorticoid receptor in the amygdala. A mineralocorticoid receptor agonist reversed the effects of D-pinitol on fear extinction and recall, and the antagonistic property of Dpinitol against the mineralocorticoid receptor was confirmed in vitro. Our findings suggest that D-pinitol could serve as a potential therapeutic agent for PTSD due to its antagonistic effect on the mineralocorticoid receptor.
Keywords
ANIMAL-MODELS; AMYGDALA; DYSFUNCTION; FLUOXETINE; ANXIETY; TIME; FEAR; Post -traumatic stress disorder; D-Pinitol; Single prolonged stress; Amygdala; Glucocorticoid receptor; Mineralocorticoid receptor
ISSN
0278-5846
URI
https://pubs.kist.re.kr/handle/201004/149888
DOI
10.1016/j.pnpbp.2024.110990
Appears in Collections:
KIST Article > 2024
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