Specific knockout of Sox2 in astrocytes reduces reactive astrocyte formation and promotes recovery after early postnatal traumatic brain injury in mouse cortex. Issue 3 (10th November 2022)

• Record Type: Journal Article
• Authors: Liu, Yitong; Hong, Wentong; Gong, Pifang; Qi, Guibo; Wang, Xiaoxuan; Kang, Siying; Tang, Han; Qin, Song
• Is Part Of: Glia. Volume 71:Issue 3(2023)
• Page Start: 602
• Page End: 615
• Publication Date: 2022-11-10
• Subjects: brain recovery -- reactive astrocytes -- Sox2 -- traumatic brain injury; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.24298
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract: In response to central nervous system (CNS) injury, astrocytes go through a series of alterations, referred to as reactive astrogliosis, ranging from changes in gene expression and cell hypertrophy to permanent astrocyte borders around stromal cell scars in CNS lesions. The mechanisms underlying injury‐induced reactive astrocytes in the adult CNS have been extensively studied. However, little is known about injury‐induced reactive astrocytes during early postnatal development. Astrocytes in the mouse cortex are mainly produced through local proliferation during the first 2 weeks after birth. Here we show that Sox2, a transcription factor critical for stem cells and brain development, is expressed in the early postnatal astrocytes and its expression level was increased in reactive astrocytes after traumatic brain injury (TBI) at postnatal day (P) 7 in the cortex. Using a tamoxifen‐induced hGFAP‐CreERT2; Sox2 flox/flox ; Rosa‐tdT mouse model, we found that specific knockout of Sox2 in astrocytes greatly inhibited the proliferation of reactive astrocytes, the formation of glia limitans borders and subsequently promoted the tissue recovery after postnatal TBI at P7 in the cortex. In addition, we found that injury‐induced glia limitans borders were still formed at P2 in the wild‐type mouse cortex, and knockout of Sox2 in astrocytes inhibited the reactivity of both astrocytes and microglia. Together, these findings provide evidence that Sox2 is essential for the reactivity of astrocytes in response to the cortical TBI during the early postnatal period and suggest that Sox2‐dependent astrocyte reactivity is a potential target for therapeutic treatment after TBI. Main Points: Sox2 expression is upregulated in reactive astrocytes after early postnatal traumatic brain injury (TBI). Astrocyte‐specific knockout of Sox2 inhibits proliferation of reactive astrocytes and promotes tissue recovery after early postnatal TBI.