Protective role of melatonin against white matter lesions induced by chronic cerebral hypoperfusion in rats

Abstract

Objective To observe the protective function and mechanism of melatonin(MT)against white matter lesions in corpus callosum induced by chronic cerebral hypoperfusion (CCH) in cerebral small vessel disease (cSVD) rats. Methods Forty⁃four adult male Sprague⁃Dawley rats were divided into sham group, bilateral common carotid artery occlusion (BCCAO) group, MT1 group [BCCAO+melatonin 5mg/(kg·d)]andMT2group[BCCAO+melatonin10mg/(kg·d)]. Four weeks after operation,social activity (sniffing time and crossing number) was assessed to reflect apathetic behavior. Myelin basic protein(MBP) in corpus callosum was detected by immunofluorescence. Transmission electron microscope was used to comparetheG-ratio. Western blotting test was used to detect phosphorylation level of mammalian target of rapamycin (mTOR). Results BCCAO group rats showed fewer sniffing time (t=58.000, P=0.000) and crossing number(t=20.000, P=0.000),lower level of MBP expression(t=20.400, P=0.000),higherlevel ofG⁃ratio(t=-9.800, P=0.000),and lower pmTOR/mTOR ratio(t=20.336, P=0.000)than those of sham group; after treatment of melatonin [5 or 10mg/(kg·d)], MT1 group and MT2 group showed more sniffing time(t=-12.600, P=0.001; t=-26.000, P=0.000) and crossing number(t=-8.400, P=0.000; t=-10.200, P=0.000),higher pmTOR/mTOR ratio(t=-6.022, P=0.014; t=-8.800, P=0.001)than those of BCCAO group but still lower than those of sham group(t=45.400, P=0.000; t=32.000, P=0.000; t=11.600, P= 0.000; t=9.800, P=0.000; t=14.314, P=0.000; t=11.536, P=0.000); while showed higher level of MBP expression(t=-16.800, P=0.001; t=-20.600, P=0.000),and lower leve lof G-ratio(t=8.600, P=0.041; t= 9.200, P=0.030) than those of BCCAO group but similar with sham group (P>0.05, for all); MT2 group showed longer sniffing time than MT1 group (t =-13.400, P =0.000). Conclusions Melatonin could ameliorate apathetic behavioral and white matter lesions in corpu callosums in rats withc SVD,which might be related to the up-regulate of phosphorylation level of mTOR.

Keywords

• Cerebral small vessel diseases; Melantonin; White matter; Disease models
• animals