Mice deficient in transmembrane prostatic acid phosphatase display increased GABAergic transmission and neurological alterations.

Prostatic acid phosphatase (PAP), the first diagnostic marker and present therapeutic target for prostate cancer, modulates nociception at the dorsal root ganglia (DRG), but its function in the central nervous system has remained unknown. We studied expression and function of TMPAP (the transmembran...

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Autores principales:	Heidi O Nousiainen, Ileana B Quintero, Timo T Myöhänen, Vootele Voikar, Jelena Mijatovic, Mikael Segerstråle, Annakaisa M Herrala, Natalia Kulesskaya, Anitta E Pulkka, Tanja Kivinummi, Usama Abo-Ramadan, Tomi Taira, T Petteri Piepponen, Heikki Rauvala, Pirkko Vihko
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6b7849ad9e374ed288cb0da44ab9264c
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spelling	oai:doaj.org-article:6b7849ad9e374ed288cb0da44ab9264c2021-11-18T08:18:34ZMice deficient in transmembrane prostatic acid phosphatase display increased GABAergic transmission and neurological alterations.1932-620310.1371/journal.pone.0097851https://doaj.org/article/6b7849ad9e374ed288cb0da44ab9264c2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24846136/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Prostatic acid phosphatase (PAP), the first diagnostic marker and present therapeutic target for prostate cancer, modulates nociception at the dorsal root ganglia (DRG), but its function in the central nervous system has remained unknown. We studied expression and function of TMPAP (the transmembrane isoform of PAP) in the brain by utilizing mice deficient in TMPAP (PAP-/- mice). Here we report that TMPAP is expressed in a subpopulation of cerebral GABAergic neurons, and mice deficient in TMPAP show multiple behavioral and neurochemical features linked to hyperdopaminergic dysregulation and altered GABAergic transmission. In addition to increased anxiety, disturbed prepulse inhibition, increased synthesis of striatal dopamine, and augmented response to amphetamine, PAP-deficient mice have enlarged lateral ventricles, reduced diazepam-induced loss of righting reflex, and increased GABAergic tone in the hippocampus. TMPAP in the mouse brain is localized presynaptically, and colocalized with SNARE-associated protein snapin, a protein involved in synaptic vesicle docking and fusion, and PAP-deficient mice display altered subcellular distribution of snapin. We have previously shown TMPAP to reside in prostatic exosomes and we propose that TMPAP is involved in the control of GABAergic tone in the brain also through exocytosis, and that PAP deficiency produces a distinct neurological phenotype.Heidi O NousiainenIleana B QuinteroTimo T MyöhänenVootele VoikarJelena MijatovicMikael SegerstråleAnnakaisa M HerralaNatalia KulesskayaAnitta E PulkkaTanja KivinummiUsama Abo-RamadanTomi TairaT Petteri PiepponenHeikki RauvalaPirkko VihkoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e97851 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Heidi O Nousiainen Ileana B Quintero Timo T Myöhänen Vootele Voikar Jelena Mijatovic Mikael Segerstråle Annakaisa M Herrala Natalia Kulesskaya Anitta E Pulkka Tanja Kivinummi Usama Abo-Ramadan Tomi Taira T Petteri Piepponen Heikki Rauvala Pirkko Vihko Mice deficient in transmembrane prostatic acid phosphatase display increased GABAergic transmission and neurological alterations.
description	Prostatic acid phosphatase (PAP), the first diagnostic marker and present therapeutic target for prostate cancer, modulates nociception at the dorsal root ganglia (DRG), but its function in the central nervous system has remained unknown. We studied expression and function of TMPAP (the transmembrane isoform of PAP) in the brain by utilizing mice deficient in TMPAP (PAP-/- mice). Here we report that TMPAP is expressed in a subpopulation of cerebral GABAergic neurons, and mice deficient in TMPAP show multiple behavioral and neurochemical features linked to hyperdopaminergic dysregulation and altered GABAergic transmission. In addition to increased anxiety, disturbed prepulse inhibition, increased synthesis of striatal dopamine, and augmented response to amphetamine, PAP-deficient mice have enlarged lateral ventricles, reduced diazepam-induced loss of righting reflex, and increased GABAergic tone in the hippocampus. TMPAP in the mouse brain is localized presynaptically, and colocalized with SNARE-associated protein snapin, a protein involved in synaptic vesicle docking and fusion, and PAP-deficient mice display altered subcellular distribution of snapin. We have previously shown TMPAP to reside in prostatic exosomes and we propose that TMPAP is involved in the control of GABAergic tone in the brain also through exocytosis, and that PAP deficiency produces a distinct neurological phenotype.
format	article
author	Heidi O Nousiainen Ileana B Quintero Timo T Myöhänen Vootele Voikar Jelena Mijatovic Mikael Segerstråle Annakaisa M Herrala Natalia Kulesskaya Anitta E Pulkka Tanja Kivinummi Usama Abo-Ramadan Tomi Taira T Petteri Piepponen Heikki Rauvala Pirkko Vihko
author_facet	Heidi O Nousiainen Ileana B Quintero Timo T Myöhänen Vootele Voikar Jelena Mijatovic Mikael Segerstråle Annakaisa M Herrala Natalia Kulesskaya Anitta E Pulkka Tanja Kivinummi Usama Abo-Ramadan Tomi Taira T Petteri Piepponen Heikki Rauvala Pirkko Vihko
author_sort	Heidi O Nousiainen
title	Mice deficient in transmembrane prostatic acid phosphatase display increased GABAergic transmission and neurological alterations.
title_short	Mice deficient in transmembrane prostatic acid phosphatase display increased GABAergic transmission and neurological alterations.
title_full	Mice deficient in transmembrane prostatic acid phosphatase display increased GABAergic transmission and neurological alterations.
title_fullStr	Mice deficient in transmembrane prostatic acid phosphatase display increased GABAergic transmission and neurological alterations.
title_full_unstemmed	Mice deficient in transmembrane prostatic acid phosphatase display increased GABAergic transmission and neurological alterations.
title_sort	mice deficient in transmembrane prostatic acid phosphatase display increased gabaergic transmission and neurological alterations.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/6b7849ad9e374ed288cb0da44ab9264c
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Mice deficient in transmembrane prostatic acid phosphatase display increased GABAergic transmission and neurological alterations.

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