Details

Autor(en) / Beteiligte

• Xu, Shuang‐Feng
• Pang, Zhong‐Qiu
• Fan, Yong‐Gang
• Zhang, Yan‐Hui
• Meng, Yu‐Han
• Bai, Chen‐Yang
• Jia, Meng‐Yu
• Chen, Yan‐Hong
• Wang, Zhan‐You
• Guo, Chuang

Titel

Astrocyte‐specific loss of lactoferrin influences neuronal structure and function by interfering with cholesterol synthesis

Ist Teil von

• Glia, 2022-12, Vol.70 (12), p.2392-2408

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2022

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Growing evidence indicates that circulating lactoferrin (Lf) is implicated in peripheral cholesterol metabolism disorders. It has emerged that the distribution of Lf changes in astrocytes of aging brains and those exhibiting neurodegeneration; however, its physiological and/or pathological role remains unknown. Here, we demonstrate that astrocyte‐specific knockout of Lf (designated cKO) led to decreased body weight and cognitive abnormalities during early life in mice. Accordingly, there was a reduction in neuronal outgrowth and synaptic structure in cKO mice. Importantly, Lf deficiency in the primary astrocytes led to decreased sterol regulatory element binding protein 2 (Srebp2) activation and cholesterol production, and cholesterol content in cKO mice and/or in astrocytes was restored by exogenous Lf or a Srebp2 agonist. Moreover, neuronal dendritic complexity and total dendritic length were decreased after culture with the culture medium of the primary astrocytes derived from cKO mice and that this decrease was reversed after cholesterol supplementation. Alternatively, these alterations were associated with an activation of AMP‐activated protein kinase (AMPK) and inhibition of SREBP2 nuclear translocation. These data suggest that astrocytic Lf might directly or indirectly control in situ cholesterol synthesis, which may be implicated in neurodevelopment and several neurological diseases. Main Points Astrocytic lactoferrin (Lf) loss causes growth retardation and intellectual disabilities in mice. Astrocytic Lf loss leads to a reduction in neuronal outgrowth and synaptic structure. • Astrocytic lactoferrin controls in situ cholesterol synthesis in mice.