In cultured NSCs/NPCs, LTa1ß2 stimulation induced an activation of classical and non-classical NF¿B signaling. The expression of LTßR-like immunoreactivity in GFAP+/Sox2+ NSCs was identified in well-established neurogenic zones of adult mouse brain. Quantitative RT-PCR and Western blot analysis validated the expression of LTßR in cultured NSCs/NPCs and brain neurogenic regions. LTßR expression was significantly increased during neural induction. LTa1ß2 stimulation in cultured NSCs/NPCs promoted astroglial and oligodendrocytic lineage differentiation, but inhibited neuronal lineage differentiation. Astroglial NF¿B inactivation in GFAP-dnI¿Ba transgenic mice rescued LTßR-mediated abnormal phenotypes of cultured NSCs/NPCs.

Conclusion

This study provides the first evidence for the expression and function of LTßR signaling in NSCs/NPCs. Activation of LTßR signaling promotes glial lineage differentiation. Our results suggest that neurogenesis is regulated by the adaptive immunity and inflammatory responses.

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