Neuronal regeneration in the area postrema of adult mouse medulla oblongata following glutamate-induced neuronal elimination

Neural stem cells and/or progenitor cells (NSCs/NPCs) in the subventricular and subgranular zones of the adult mammal forebrain generate new neurons and are involved in partial repair after injury. Recently, NSCs/NPCs were identified in the area postrema (AP) of the medulla oblongata of the hindbrain. In this study, we used the properties of fenestrate capillaries to observe specific neuronal elimination in the AP of adult mice and investigated subsequent neuronal regeneration by neurogenesis. Subcutaneous administration of monosodium glutamate (MSG) induced prominent Fos expression in HuC/D⁺ neurons in the AP 2 h after administration. MSG administration caused a marked decrease in HuC/D⁺ neuronal density by neuronal death 3 to 21 days after administration, which recovered to the control level 35 days later. After MSG administration, the density of TUNEL⁺ dying neurons and phagocytic microglia surrounding or engulfing neurons increased. Within 7 days of MSG administration, the number of BrdU⁺　Sox2⁺ and BrdU⁺ Math1⁺ cells increased markedly, and at least the BrdU⁺ Math1⁺ cells similarly increased for the next following 7 days. A remarkable number of HuC/D⁺ neurons with BrdU⁺ nuclei were observed 35 days after MSG administration. This study reveals that neurogenesis occurs in the AP of adult mice, recovering and maintaining normal neuronal density after neuronal death.