Pregnenolone rescues schizophrenia-like behavior in dopamine transporter knockout mice.

Pregnenolone belongs to a class of endogenous neurosteroids in the central nervous system (CNS), which has been suggested to enhance cognitive functions through GABA(A) receptor signaling by its metabolites. It has been shown that the level of pregnenolone is altered in certain brain areas of schizo...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Peiyan Wong, Cecilia Chin Roei Chang, Christine E Marx, Marc G Caron, William C Wetsel, Xiaodong Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/45b2fcd0322c4ab19a4b2bc35f37e425
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:45b2fcd0322c4ab19a4b2bc35f37e425
record_format	dspace
spelling	oai:doaj.org-article:45b2fcd0322c4ab19a4b2bc35f37e4252021-11-18T08:05:34ZPregnenolone rescues schizophrenia-like behavior in dopamine transporter knockout mice.1932-620310.1371/journal.pone.0051455https://doaj.org/article/45b2fcd0322c4ab19a4b2bc35f37e4252012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23240026/?tool=EBIhttps://doaj.org/toc/1932-6203Pregnenolone belongs to a class of endogenous neurosteroids in the central nervous system (CNS), which has been suggested to enhance cognitive functions through GABA(A) receptor signaling by its metabolites. It has been shown that the level of pregnenolone is altered in certain brain areas of schizophrenic patients, and clozapine enhances pregnenolone in the CNS in rats, suggesting that pregnenolone could be used to treat certain symptoms of schizophrenia. In addition, early phase proof-of-concept clinical trials have indicated that pregnenolone is effective in reducing the negative symptoms and cognitive deficits of schizophrenia patients. Here, we evaluate the actions of pregnenolone on a mouse model for schizophrenia, the dopamine transporter knockout mouse (DAT KO). DAT KO mice mirror certain symptoms evident in patients with schizophrenia, such as the psychomotor agitation, stereotypy, deficits of prepulse inhibition and cognitive impairments. Following acute treatment, pregnenolone was found to reduce the hyperlocomotion, stereotypic bouts and pre-pulse inhibition (PPI) deficits in DAT KO mice in a dose-dependent manner. At 60 mg/kg of pregnenolone, there were no significant differences in locomotor activities and stereotypy between wild-type and DAT KO mice. Similarly, acute treatment of 60 mg/kg of pregnenolone fully rescued PPI deficits of DAT KO mice. Following chronic treatment with pregnenolone at 60 mg/kg, the cognitive deficits of DAT KO mice were rescued in the paradigms of novel object recognition test and social transmission of food preference test. Pregnenolone thus holds promise as a therapeutic candidate in schizophrenia.Peiyan WongCecilia Chin Roei ChangChristine E MarxMarc G CaronWilliam C WetselXiaodong ZhangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e51455 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Peiyan Wong Cecilia Chin Roei Chang Christine E Marx Marc G Caron William C Wetsel Xiaodong Zhang Pregnenolone rescues schizophrenia-like behavior in dopamine transporter knockout mice.
description	Pregnenolone belongs to a class of endogenous neurosteroids in the central nervous system (CNS), which has been suggested to enhance cognitive functions through GABA(A) receptor signaling by its metabolites. It has been shown that the level of pregnenolone is altered in certain brain areas of schizophrenic patients, and clozapine enhances pregnenolone in the CNS in rats, suggesting that pregnenolone could be used to treat certain symptoms of schizophrenia. In addition, early phase proof-of-concept clinical trials have indicated that pregnenolone is effective in reducing the negative symptoms and cognitive deficits of schizophrenia patients. Here, we evaluate the actions of pregnenolone on a mouse model for schizophrenia, the dopamine transporter knockout mouse (DAT KO). DAT KO mice mirror certain symptoms evident in patients with schizophrenia, such as the psychomotor agitation, stereotypy, deficits of prepulse inhibition and cognitive impairments. Following acute treatment, pregnenolone was found to reduce the hyperlocomotion, stereotypic bouts and pre-pulse inhibition (PPI) deficits in DAT KO mice in a dose-dependent manner. At 60 mg/kg of pregnenolone, there were no significant differences in locomotor activities and stereotypy between wild-type and DAT KO mice. Similarly, acute treatment of 60 mg/kg of pregnenolone fully rescued PPI deficits of DAT KO mice. Following chronic treatment with pregnenolone at 60 mg/kg, the cognitive deficits of DAT KO mice were rescued in the paradigms of novel object recognition test and social transmission of food preference test. Pregnenolone thus holds promise as a therapeutic candidate in schizophrenia.
format	article
author	Peiyan Wong Cecilia Chin Roei Chang Christine E Marx Marc G Caron William C Wetsel Xiaodong Zhang
author_facet	Peiyan Wong Cecilia Chin Roei Chang Christine E Marx Marc G Caron William C Wetsel Xiaodong Zhang
author_sort	Peiyan Wong
title	Pregnenolone rescues schizophrenia-like behavior in dopamine transporter knockout mice.
title_short	Pregnenolone rescues schizophrenia-like behavior in dopamine transporter knockout mice.
title_full	Pregnenolone rescues schizophrenia-like behavior in dopamine transporter knockout mice.
title_fullStr	Pregnenolone rescues schizophrenia-like behavior in dopamine transporter knockout mice.
title_full_unstemmed	Pregnenolone rescues schizophrenia-like behavior in dopamine transporter knockout mice.
title_sort	pregnenolone rescues schizophrenia-like behavior in dopamine transporter knockout mice.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/45b2fcd0322c4ab19a4b2bc35f37e425
work_keys_str_mv	AT peiyanwong pregnenolonerescuesschizophrenialikebehaviorindopaminetransporterknockoutmice AT ceciliachinroeichang pregnenolonerescuesschizophrenialikebehaviorindopaminetransporterknockoutmice AT christineemarx pregnenolonerescuesschizophrenialikebehaviorindopaminetransporterknockoutmice AT marcgcaron pregnenolonerescuesschizophrenialikebehaviorindopaminetransporterknockoutmice AT williamcwetsel pregnenolonerescuesschizophrenialikebehaviorindopaminetransporterknockoutmice AT xiaodongzhang pregnenolonerescuesschizophrenialikebehaviorindopaminetransporterknockoutmice
_version_	1718422224707256320

Pregnenolone rescues schizophrenia-like behavior in dopamine transporter knockout mice.

Ejemplares similares