BAF45D Downregulation in Spinal Cord Ependymal Cells Following Spinal Cord Injury in Adult Rats and Its Potential Role in the Development of Neuronal Lesions

Abstract

The endogenous spinal cord ependymal cells (SCECs), which form the central canal (CC), are critically involved in proliferation, differentiation and migration after spinal cord injury (SCI) and represents a repair cell source in treating SCI. Previously, we reported that BAF45D is expressed in the SCECs and the spinal cord neurons in adult mice and knockdown of BAF45D fail to induce expression of PAX6, a neurogenic fate determinant, during early neural differentiation of human embryonic stem cells. However, the effects of SCI on expression of BAF45D have not been reported. The aim of this study is to explore the expression and potential role of BAF45D in rat SCI model. In this study, adult rats were randomly divided into intact, sham, and SCI groups. We first explored expression of BAF45D in the SCECs in intact adult rats. We then explored SCI-induced loss of motor neurons and lesion of neurites in the anterior horns induced by the SCI. We also investigated whether the SCI-induced lesions in SCECs are accompanied by the motor neuron lesions. Finally, we examined the effect of BAF45D knockdown on cell growth in neuro2a cells. Our data showed that BAF45D is expressed in SCECs, neurons, and oligodendrocytes but not astrocytes in the spinal cords of intact adult rats. After SCI, the structure of CC was disrupted and the BAF45D-positive SCEC-derivatives were decreased. During the early stages of SCI, when shape of CC was affected but there was no disruption in circular structure of the SCECs, it was evident that there was a significant reduction in the number of neurites and motor neurons in the anterior horns compared with those of intact rats. In comparison, a complete loss of SCECs accompanied by further loss of motor neurons but not neurites was observed at the later stage. BAF45D knockdown was also found to inhibit cell growth in neuro2a cells. These results highlight the decreased expression of BAF45D in SCI-injured SCECs and the potential role of BAF45D downregulation in development of neuronal lesion after SCI in adult rats.

In-vitro differentiation of human embryonic stem cells into spinal cord neural stem cells

“…H9 cells induced under Matrigel matrix gel-coated conditions downregulated OCT4 and expressed PAX6, NESTIN, SOX1 and other NSC markers. WNT25 and SHH are potent mitogens in the developing spinal cord [25]. After neural induction, we continued to inhibit SMAD and antagonize SHH and successfully obtained spinal cord NSCs with HOX-C protein family positivity.…”

Role of brahma-related gene 1/brahma-associated factor subunits in neural stem/progenitor cells and related neural developmental disorders

“…It has been reported that postmitotic neurons express BAF45B/C protein but lack the paralogous BAF45A/D, which confers neuronal properties[ 25 - 27 , 41 ]. The protein expression of BAF45D in adult rat NSPCs and neurons but not astrocytes may imply a role for BAF45D in the differentiation of NSPCs[ 44 ].…”

Neurogenesis as a Tool for Spinal Cord Injury

“…In the spinal cord, BAF45D is expressed in SCECs, neurons and oligodendrocytes, but not in astrocytes. After SCI, the expression of BAF45D in SCECs is decreased, and thus, proliferating SCECs mainly differentiate into astrocytes instead of neurons [ 50 ]. Therefore, the targeting of this peptide may be another potential way to affect neurogenesis after an SCI.…”