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Astrocytes Transplanted during Early Postnatal Development Integrate, Mature, and Survive Long Term in Mouse Cortex.
Chierzi, Sabrina; Kacerovsky, J Benjamin; Fok, Albert H K; Lahaie, Sylvie; Shibi Rosen, Arielle; Farmer, W Todd; Murai, Keith K.
Afiliación
  • Chierzi S; Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec H3G 1A4, Canada.
  • Kacerovsky JB; Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec H3G 1A4, Canada.
  • Fok AHK; Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec H3G 1A4, Canada.
  • Lahaie S; Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec H3G 1A4, Canada.
  • Shibi Rosen A; Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec H3G 1A4, Canada.
  • Farmer WT; Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec H3G 1A4, Canada.
  • Murai KK; Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec H3G 1A4, Canada keith.murai@mcgill.ca.
J Neurosci ; 43(9): 1509-1529, 2023 03 01.
Article en En | MEDLINE | ID: mdl-36669885
Astrocytes have complex structural, molecular, and physiological properties and form specialized microenvironments that support circuit-specific functions in the CNS. To better understand how astrocytes acquire their unique features, we transplanted immature mouse cortical astrocytes into the developing cortex of male and female mice and assessed their integration, maturation, and survival. Within days, transplanted astrocytes developed morphologies and acquired territories and tiling behavior typical of cortical astrocytes. At 35-47 d post-transplantation, astrocytes appeared morphologically mature and expressed levels of EAAT2/GLT1 similar to nontransplanted astrocytes. Transplanted astrocytes also supported excitatory/inhibitory (E/I) presynaptic terminals within their territories, and displayed normal Ca2+ events. Transplanted astrocytes showed initially reduced expression of aquaporin 4 (AQP4) at endfeet and elevated expression of EAAT1/GLAST, with both proteins showing normalized expression by 110 d and one year post-transplantation, respectively. To understand how specific brain regions support astrocytic integration and maturation, we transplanted cortical astrocytes into the developing cerebellum. Cortical astrocytes interlaced with Bergmann glia (BG) in the cerebellar molecular layer to establish discrete territories. However, transplanted astrocytes retained many cortical astrocytic features including higher levels of EAAT2/GLT1, lower levels of EAAT1/GLAST, and the absence of expression of the AMPAR subunit GluA1. Collectively, our findings demonstrate that immature cortical astrocytes integrate, mature, and survive (more than one year) following transplantation and retain cortical astrocytic properties. Astrocytic transplantation can be useful for investigating cell-autonomous (intrinsic) and non-cell-autonomous (environmental) mechanisms contributing to astrocytic development/diversity, and for determining the optimal timing for transplanting astrocytes for cellular delivery or replacement in regenerative medicine.SIGNIFICANCE STATEMENT The mechanisms that enable astrocytes to acquire diverse molecular and structural properties remain to be better understood. In this study, we systematically analyzed the properties of cortical astrocytes following their transplantation to the early postnatal brain. We found that immature cortical astrocytes transplanted into cerebral cortex during early postnatal mouse development integrate and establish normal astrocytic properties, and show long-term survival in vivo (more than one year). In contrast, transplanted cortical astrocytes display reduced or altered ability to integrate into the more mature cerebral cortex or developing cerebellum, respectively. This study demonstrates the developmental potential of transplanted cortical astrocytes and provides an approach to tease apart cell-autonomous (intrinsic) and non-cell-autonomous (environmental) mechanisms that determine the structural, molecular, and physiological phenotype of astrocytes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neuroglía / Astrocitos Límite: Animals Idioma: En Revista: J Neurosci Año: 2023 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neuroglía / Astrocitos Límite: Animals Idioma: En Revista: J Neurosci Año: 2023 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos