Minocycline reduces neuroinflammation but does not ameliorate neuron loss in a mouse model of neurodegeneration.

Shanshan Cheng,Zhenyu Yin,Jinxing Hou,Guiquan Chen,Long Wang,Yun Shi,Huahong Yu,Chen Zhang,Congyu Xu,Xiaoxia Zou

doi:10.1038/srep10535

Abstract

Minocycline is a broad-spectrum tetracycline antibiotic. A number of preclinical studies have shown that minocycline exhibits neuroprotective effects in various animal models of neurological diseases. However, it remained unknown whether minocycline is effective to prevent neuron loss. To systematically evaluate its effects, minocycline was used to treat Dicer conditional knockout (cKO) mice which display age-related neuron loss. The drug was given to mutant mice prior to the occurrence of neuroinflammation and neurodegeneration, and the treatment had lasted 2 months. Levels of inflammation markers, including glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule1 (Iba1) and interleukin6 (IL6), were significantly reduced in minocycline-treated Dicer cKO mice. In contrast, levels of neuronal markers and the total number of apoptotic cells in Dicer cKO mice were not affected by the drug. In summary, inhibition of neuroinflammation by minocycline is insufficient to prevent neuron loss and apoptosis.

Highlights

Since it has been unknown whether minocycline could be used as a valuable anti-neurodegeneration drug for neurodegenerative disease (ND), it is of great importance to evaluate its preclinical efficacy using appropriate neurodegenerative mouse models
We did not find significant drug effect on p-Akt[473] levels (Fig. 7C: p > 0 .2). These results suggest that minocycline did not alter activities of Erk, GSK3 and Akt. It remained unknown whether minocycline is an effective drug to prevent or to stop neuron loss in neurodegenerative diseases
We have shown that the treatment of minocycline successfully reduced neuroinflammatory responses but failed to ameliorate neuron loss and apoptosis

Summary

Introduction

Neuroinflammation is believed to be a driving force for neurodegeneration[17], raising the possibility that the early use of anti-inflammation drugs may prevent neuron loss. Several studies have demonstrated that minocycline inhibits neuroinflammation and neuron death in mouse models of AD with amyloid plaques[20,21], ALS22, HD23, PD24, Down’s syndrome[25], and stroke[26,27]. The evidence above indicates that minocycline is effective to reduce plaque and tangle pathology. Since it has been unknown whether minocycline could be used as a valuable anti-neurodegeneration drug for ND, it is of great importance to evaluate its preclinical efficacy using appropriate neurodegenerative mouse models. We found that neuroinflammation was effectively inhibited, and that neuron loss and apoptosis were not ameliorated

Methods

Results

Conclusion