The Effect Of Minocycline To Neuron Loss In The Neurondengenration Mouse Model

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.First, we determined the neuroinflammation and neuron loss appear in Dicer cKO mouse and 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 calciumbinding adapter molecule1(Iba1) and interleukin6(IL6), were significantly reduced in minocyclinetreated Dicer cKO mice, suggested that minocycline could inhibition the neuroinflammation.In contrast, levels of neuronal nuclear(NeuN), synaptophysin(SYP), postsynaptic Density protein 95(PSD95) and transferase-mediated deoxyuridine triphosphate-biotin nick end labeling(TUNEL), the result indicated that neuronal markers and the total number of apoptotic cells in Dicer cKO mice were not affected by the drug, minocycline did not effect the neuronal loss.Tau hyperphosphorylation occurrence in Dicer cKO mice, however, minocycline did not reduce tau hyperphosphorylation in Dicer cKO mice. Levels of the phosphorylation-Tau associative protein kinase including mitogen-activated protein kinases p44/42(MAPK p44/42 or Erk1/2), glycogen synthase kinase 3(Gsk3), protein kinase B(Akt), the Tau kinase did not drug effect, these results suggest that minocycline did not alter activities of Erk, Gsk3 and Akt.In summary, inhibition of neuroinflammation by minocycline is insufficient to prevent neuron loss and apoptosis.