Glutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance

Glutamate carboxypeptidase II (GCPII) expression in brain is increased by inflammation, and reduces NAAG (N-acetyl aspartyl glutamate) stimulation of mGluR3 signaling. Genetic insults in this signaling cascade are increasingly linked to cognitive disorders in humans, where increased GCPII and or dec...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Dibyadeep Datta, Shannon N. Leslie, Elizabeth Woo, Nishita Amancharla, Ayah Elmansy, Miguel Lepe, Adam P. Mecca, Barbara S. Slusher, Angus C. Nairn, Amy F. T. Arnsten
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	NAALADase FOLH1 mGluR3 GRM3 inflammation 2-MPPA Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/c3772190e75c4cda940b9539cf4e6655
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c3772190e75c4cda940b9539cf4e6655
record_format	dspace
spelling	oai:doaj.org-article:c3772190e75c4cda940b9539cf4e66552021-11-15T04:38:48ZGlutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance1663-436510.3389/fnagi.2021.760270https://doaj.org/article/c3772190e75c4cda940b9539cf4e66552021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnagi.2021.760270/fullhttps://doaj.org/toc/1663-4365Glutamate carboxypeptidase II (GCPII) expression in brain is increased by inflammation, and reduces NAAG (N-acetyl aspartyl glutamate) stimulation of mGluR3 signaling. Genetic insults in this signaling cascade are increasingly linked to cognitive disorders in humans, where increased GCPII and or decreased NAAG-mGluR3 are associated with impaired prefrontal cortical (PFC) activation and cognitive impairment. As aging is associated with increased inflammation and PFC cognitive deficits, the current study examined GCPII and mGluR3 expression in the aging rat medial PFC, and tested whether GCPII inhibition with 2-(3-mercaptopropyl) pentanedioic acid (2-MPPA) would improve working memory performance. We found that GCPII protein was expressed on astrocytes and some microglia as expected from previous studies, but was also prominently expressed on neurons, and showed increased levels with advancing age. Systemic administration of the GCPII inhibitor, 2-MPPA, improved working memory performance in young and aged rats, and also improved performance after local infusion into the medial PFC. As GCPII inhibitors are well-tolerated, they may provide an important new direction for treatment of cognitive disorders associated with aging and/or inflammation.Dibyadeep DattaShannon N. LeslieElizabeth WooNishita AmancharlaAyah ElmansyMiguel LepeAdam P. MeccaBarbara S. SlusherAngus C. NairnAmy F. T. ArnstenFrontiers Media S.A.articleNAALADaseFOLH1mGluR3GRM3inflammation2-MPPANeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Aging Neuroscience, Vol 13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	NAALADase FOLH1 mGluR3 GRM3 inflammation 2-MPPA Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	NAALADase FOLH1 mGluR3 GRM3 inflammation 2-MPPA Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Dibyadeep Datta Shannon N. Leslie Elizabeth Woo Nishita Amancharla Ayah Elmansy Miguel Lepe Adam P. Mecca Barbara S. Slusher Angus C. Nairn Amy F. T. Arnsten Glutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance
description	Glutamate carboxypeptidase II (GCPII) expression in brain is increased by inflammation, and reduces NAAG (N-acetyl aspartyl glutamate) stimulation of mGluR3 signaling. Genetic insults in this signaling cascade are increasingly linked to cognitive disorders in humans, where increased GCPII and or decreased NAAG-mGluR3 are associated with impaired prefrontal cortical (PFC) activation and cognitive impairment. As aging is associated with increased inflammation and PFC cognitive deficits, the current study examined GCPII and mGluR3 expression in the aging rat medial PFC, and tested whether GCPII inhibition with 2-(3-mercaptopropyl) pentanedioic acid (2-MPPA) would improve working memory performance. We found that GCPII protein was expressed on astrocytes and some microglia as expected from previous studies, but was also prominently expressed on neurons, and showed increased levels with advancing age. Systemic administration of the GCPII inhibitor, 2-MPPA, improved working memory performance in young and aged rats, and also improved performance after local infusion into the medial PFC. As GCPII inhibitors are well-tolerated, they may provide an important new direction for treatment of cognitive disorders associated with aging and/or inflammation.
format	article
author	Dibyadeep Datta Shannon N. Leslie Elizabeth Woo Nishita Amancharla Ayah Elmansy Miguel Lepe Adam P. Mecca Barbara S. Slusher Angus C. Nairn Amy F. T. Arnsten
author_facet	Dibyadeep Datta Shannon N. Leslie Elizabeth Woo Nishita Amancharla Ayah Elmansy Miguel Lepe Adam P. Mecca Barbara S. Slusher Angus C. Nairn Amy F. T. Arnsten
author_sort	Dibyadeep Datta
title	Glutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance
title_short	Glutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance
title_full	Glutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance
title_fullStr	Glutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance
title_full_unstemmed	Glutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance
title_sort	glutamate carboxypeptidase ii in aging rat prefrontal cortex impairs working memory performance
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/c3772190e75c4cda940b9539cf4e6655
work_keys_str_mv	AT dibyadeepdatta glutamatecarboxypeptidaseiiinagingratprefrontalcorteximpairsworkingmemoryperformance AT shannonnleslie glutamatecarboxypeptidaseiiinagingratprefrontalcorteximpairsworkingmemoryperformance AT elizabethwoo glutamatecarboxypeptidaseiiinagingratprefrontalcorteximpairsworkingmemoryperformance AT nishitaamancharla glutamatecarboxypeptidaseiiinagingratprefrontalcorteximpairsworkingmemoryperformance AT ayahelmansy glutamatecarboxypeptidaseiiinagingratprefrontalcorteximpairsworkingmemoryperformance AT miguellepe glutamatecarboxypeptidaseiiinagingratprefrontalcorteximpairsworkingmemoryperformance AT adampmecca glutamatecarboxypeptidaseiiinagingratprefrontalcorteximpairsworkingmemoryperformance AT barbarasslusher glutamatecarboxypeptidaseiiinagingratprefrontalcorteximpairsworkingmemoryperformance AT anguscnairn glutamatecarboxypeptidaseiiinagingratprefrontalcorteximpairsworkingmemoryperformance AT amyftarnsten glutamatecarboxypeptidaseiiinagingratprefrontalcorteximpairsworkingmemoryperformance
_version_	1718428829631905792

Glutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance

Ejemplares similares