Role of C/EBP-β in Methamphetamine-Mediated Microglial Apoptosis

Abstract

Methamphetamine (MA) is a widely abused psychoactive drug that primarily damages the nervous system. However, the involvement of MA in the survival of microglia remains poorly understood. CCAAT-enhancer binding protein (C/EBP-β) is a transcription factor and an important regulator of cell apoptosis. Lipocalin2 (lcn2) is a known apoptosis inducer and is involved in many cell death processes. We hypothesized that C/EBP-β is involved in MA-induced lcn2-mediated microglial apoptosis. To test this hypothesis, we measured the protein expression of C/EBP-β after MA treatment and evaluated the effects of silencing C/EBP-β or lcn2 on MA-induced apoptosis in BV-2 cells and the mouse striatum after intrastriatal MA injection. MA exposure increased the expression of C/EBP-β and stimulated the lcn2-mediated modulation of apoptosis. Moreover, silencing the C/EBP-β-dependent lcn2 upregulation reversed the MA-induced microglial apoptosis. The in vivo relevance of these findings was confirmed in mouse models, which demonstrated that the microinjection of anti-C/EBP-β into the striatum ameliorated the MA-induced decrease survival of microglia. These findings provide a new insight regarding the specific contributions of C/EBP-β-lcn2 to microglial survival in the context of MA abuse.

Natural Products in Modulating Methamphetamine-Induced Neuronal Apoptosis

“…Lastly, new and emerging insightful scientific findings on METH-induced neuronal apoptosis have continually updated our understanding of its biomechanisms. For example, recent studies confirmed that CCAAT/enhancer-binding protein (C/EBP-β), Lipocalin2 (lcn2), and Sigma-1 receptor (σ-1R) might play an important role in METH-induced microglial apoptosis ( Shen et al, 2016 ; Chen et al, 2019 ). These new findings may provide new directions for future studies of natural agents and yield more refined and robust evidence.…”

Differences in Immune-Related Genes Underlie Temporal and Regional Pathological Progression in 3xTg-AD Mice

“…So, MafB upregulation may be linked to the decrease of the inflammatory markers obtained in the 3-month-old transgenic mice. Relative to the downregulated genes, the C/EBP- β gene is, indeed, a direct target of miR-155 in this AD model [ 16 ], and its reduction is linked to a decrease in cell apoptosis [ 105 ] and delayed cell senescence [ 106 ]. On the other hand, the downregulation of Run2 , at both 3 and 9 months in the transgenic animals may lead to a reduction in microglia phagocytic ability [ 107 ].…”

The interaction of lipocalin-2 and astrocytes in neuroinflammation: mechanisms and therapeutic application

“…Furthermore, Lcn-2 can mediate apoptosis in microglia. For instance, in methamphetamine-induced striatal microglial apoptosis, the CCAAT-enhancer binding protein/Lcn-2 axis plays a critical role ( 97 ).…”