Neurodevelopmental Processes in the Prefrontal Cortex Derailed by Chronic HIV-1 Viral Protein Exposure

Due to the widespread access to, and implementation of, combination antiretroviral therapy, individuals perinatally infected with human immunodeficiency virus type 1 (HIV-1) are living into adolescence and adulthood. Perinatally infected adolescents living with HIV-1 (pALHIV) are plagued by progress...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kristen A. McLaurin, Hailong Li, Rosemarie M. Booze, Charles F. Mactutus
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	adolescence development dendritic spines human immunodeficiency virus type 1 prefrontal cortex neuroinflammation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3c2a512f4ba24c4683161aa4a4bd9e53
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3c2a512f4ba24c4683161aa4a4bd9e53
record_format	dspace
spelling	oai:doaj.org-article:3c2a512f4ba24c4683161aa4a4bd9e532021-11-25T17:10:38ZNeurodevelopmental Processes in the Prefrontal Cortex Derailed by Chronic HIV-1 Viral Protein Exposure10.3390/cells101130372073-4409https://doaj.org/article/3c2a512f4ba24c4683161aa4a4bd9e532021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3037https://doaj.org/toc/2073-4409Due to the widespread access to, and implementation of, combination antiretroviral therapy, individuals perinatally infected with human immunodeficiency virus type 1 (HIV-1) are living into adolescence and adulthood. Perinatally infected adolescents living with HIV-1 (pALHIV) are plagued by progressive, chronic neurocognitive impairments; the pathophysiological mechanisms underlying these deficits, however, remain understudied. A longitudinal experimental design from postnatal day (PD) 30 to PD 180 was utilized to establish the development of pyramidal neurons, and associated dendritic spines, from layers II-III of the medial prefrontal cortex (mPFC) in HIV-1 transgenic (Tg) and control animals. Three putative neuroinflammatory markers (i.e., IL-1β, IL-6, and TNF-α) were evaluated early in development (i.e., PD 30) as a potential mechanism underlying synaptic dysfunction in the mPFC. Constitutive expression of HIV-1 viral proteins induced prominent neurodevelopmental alterations and progressive synaptodendritic dysfunction, independent of biological sex, in pyramidal neurons from layers II-III of the mPFC. From a neurodevelopmental perspective, HIV-1 Tg rats exhibited prominent deficits in dendritic and synaptic pruning. With regards to progressive synaptodendritic dysfunction, HIV-1 Tg animals exhibited an age-related population shift towards dendritic spines with decreased volume, increased backbone length, and decreased head diameter; parameters associated with a more immature dendritic spine phenotype. There was no compelling evidence for neuroinflammation in the mPFC during early development. Collectively, progressive neuronal and dendritic spine dysmorphology herald synaptodendritic dysfunction as a key neural mechanism underlying chronic neurocognitive impairments in pALHIV.Kristen A. McLaurinHailong LiRosemarie M. BoozeCharles F. MactutusMDPI AGarticleadolescencedevelopmentdendritic spineshuman immunodeficiency virus type 1prefrontal cortexneuroinflammationBiology (General)QH301-705.5ENCells, Vol 10, Iss 3037, p 3037 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adolescence development dendritic spines human immunodeficiency virus type 1 prefrontal cortex neuroinflammation Biology (General) QH301-705.5
spellingShingle	adolescence development dendritic spines human immunodeficiency virus type 1 prefrontal cortex neuroinflammation Biology (General) QH301-705.5 Kristen A. McLaurin Hailong Li Rosemarie M. Booze Charles F. Mactutus Neurodevelopmental Processes in the Prefrontal Cortex Derailed by Chronic HIV-1 Viral Protein Exposure
description	Due to the widespread access to, and implementation of, combination antiretroviral therapy, individuals perinatally infected with human immunodeficiency virus type 1 (HIV-1) are living into adolescence and adulthood. Perinatally infected adolescents living with HIV-1 (pALHIV) are plagued by progressive, chronic neurocognitive impairments; the pathophysiological mechanisms underlying these deficits, however, remain understudied. A longitudinal experimental design from postnatal day (PD) 30 to PD 180 was utilized to establish the development of pyramidal neurons, and associated dendritic spines, from layers II-III of the medial prefrontal cortex (mPFC) in HIV-1 transgenic (Tg) and control animals. Three putative neuroinflammatory markers (i.e., IL-1β, IL-6, and TNF-α) were evaluated early in development (i.e., PD 30) as a potential mechanism underlying synaptic dysfunction in the mPFC. Constitutive expression of HIV-1 viral proteins induced prominent neurodevelopmental alterations and progressive synaptodendritic dysfunction, independent of biological sex, in pyramidal neurons from layers II-III of the mPFC. From a neurodevelopmental perspective, HIV-1 Tg rats exhibited prominent deficits in dendritic and synaptic pruning. With regards to progressive synaptodendritic dysfunction, HIV-1 Tg animals exhibited an age-related population shift towards dendritic spines with decreased volume, increased backbone length, and decreased head diameter; parameters associated with a more immature dendritic spine phenotype. There was no compelling evidence for neuroinflammation in the mPFC during early development. Collectively, progressive neuronal and dendritic spine dysmorphology herald synaptodendritic dysfunction as a key neural mechanism underlying chronic neurocognitive impairments in pALHIV.
format	article
author	Kristen A. McLaurin Hailong Li Rosemarie M. Booze Charles F. Mactutus
author_facet	Kristen A. McLaurin Hailong Li Rosemarie M. Booze Charles F. Mactutus
author_sort	Kristen A. McLaurin
title	Neurodevelopmental Processes in the Prefrontal Cortex Derailed by Chronic HIV-1 Viral Protein Exposure
title_short	Neurodevelopmental Processes in the Prefrontal Cortex Derailed by Chronic HIV-1 Viral Protein Exposure
title_full	Neurodevelopmental Processes in the Prefrontal Cortex Derailed by Chronic HIV-1 Viral Protein Exposure
title_fullStr	Neurodevelopmental Processes in the Prefrontal Cortex Derailed by Chronic HIV-1 Viral Protein Exposure
title_full_unstemmed	Neurodevelopmental Processes in the Prefrontal Cortex Derailed by Chronic HIV-1 Viral Protein Exposure
title_sort	neurodevelopmental processes in the prefrontal cortex derailed by chronic hiv-1 viral protein exposure
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3c2a512f4ba24c4683161aa4a4bd9e53
work_keys_str_mv	AT kristenamclaurin neurodevelopmentalprocessesintheprefrontalcortexderailedbychronichiv1viralproteinexposure AT hailongli neurodevelopmentalprocessesintheprefrontalcortexderailedbychronichiv1viralproteinexposure AT rosemariembooze neurodevelopmentalprocessesintheprefrontalcortexderailedbychronichiv1viralproteinexposure AT charlesfmactutus neurodevelopmentalprocessesintheprefrontalcortexderailedbychronichiv1viralproteinexposure
_version_	1718412642148679680

Neurodevelopmental Processes in the Prefrontal Cortex Derailed by Chronic HIV-1 Viral Protein Exposure

Ejemplares similares