Intranasal iron administration induces iron deposition,immunoactivation,and cell-specific vulnerability in the olfactory bulb of C57BL/6 mice  

作　　者：Xiao-Qing Mi Bao-Chen Liu Le Qu Yu Yuan Hui Li Ao-Yang Xu Yu-Lin Zhang Jun-Xia Xie Ning Song 

机构地区：[1]School of Basic Medicine,Institute of Brain Science and Disease,Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Brain Diseases,Qingdao University,Qingdao,Shandong,266071,China [2]School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China

出　　处：《Zoological Research》2025年第1期209-224,共16页动物学研究(英文)

基　　金：supported by the National Natural Science Foundation of China (32471188,32170984,82301787)。

摘　　要：Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function;however,its abnormal accumulation is also implicated in various neurological disorders.The olfactory bulb(OB),an early target in neurodegenerative diseases,acts as a gateway for environmental toxins and contains diverse neuronal populations with distinct roles.This study explored the cell-specific vulnerability to iron in the OB using a mouse model of intranasal administration of ferric ammonium citrate(FAC).Olfactory function was assessed through olfactory discrimination tests,while iron levels in OB tissues,cerebrospinal fluid(CSF),and serum were quantified using inductively coupled plasma mass spectrometry(ICP-MS),immunohistochemical staining,and iron assays.Transcriptomic changes and immune responses were assessed using RNA sequencing and immune cell infiltration analysis.Results showed that intranasal FAC administration impaired olfactory function,accompanied by iron deposition in the olfactory mucosa and OB,as well as damage to olfactory sensory neurons.Notably,these effects occurred without elevations in CSF or serum iron levels.OB iron accumulation activated multiple immune cells,including microglia and astrocytes,but did not trigger ferroptosis.Spatial transcriptomic sequencing of healthy adult mouse OBs revealed significant cellular heterogeneity,with an abundance of neuroglia and neurons.Among neurons,GABAergic neurons were the most prevalent,followed by glutamatergic and dopaminergic neurons,while cholinergic and serotonergic neurons were sparsely distributed.Under iron-stressed conditions,oligodendrocytes,dopaminergic neurons,and glutamatergic neurons exhibited significant damage,while GABAergic neurons remained unaffected.These findings highlight the selective vulnerability of neuronal and glial populations to iron-induced stress,offering novel insights into the loss of specific cell types in the OB during iron dysregulation.

关 键 词：Intranasal administration Olfactory bulb IRON Ferroptosis Immune response 

分 类 号：R741[医药卫生—神经病学与精神病学]