Objective To investigate the effects and related mechanism of lead (Pb) exposure on learning and memory ability of senescence accelerated mice (SAMP8).
Methods Twenty male SAMP8 mice and 20 male SAMR1 mice were randomly divided into four groups:SAMR1, SAMR1+Pb exposure, SAMP8, and SAMP8+Pb exposure groups. Mice in the SAMR1+Pb exposure group and the SAMP8+Pb exposure group were treated with 0.05 g/L lead acetate via drinking water for nine weeks, and mice in the SAMR1 group and the SAMP8 group were given 0.05 g/L sodium acetate via drinking water for nine weeks. Morris water maze experiment was applied to test learning and memory ability. Protein expressions of amyloid precursor protein (APP), doublecortin (DCX), and glial fibrillary acidic protein (GFAP) in subventricular zone (SVZ) were observed by immunofluorescence, and the cell counts of neuronal progenitors and astrocytes were analyzed. The mRNA expressions of DCX, GFAP, and brain-derived neurophic factor (BDNF) in SVZ were detected by quantitative real-time PCR.
Results The results of Morris water maze test on day 3 showed that, compared with the SAMR1 group(10.94±3.98) s, the escape latencies of the SAMR1+Pb exposure group(34.15±6.78) s, the SAMP8 group(29.24±6.15) s, and the SAMP8+Pb exposure group(50.86±8.56) s were increased (P < 0.05); compared with the SAMP8 group and the SAMR1+Pb exposure group, the escape latency of the SAMP8+Pb exposure group was extented (P < 0.05); the number of platform crossings were 6.75±1.28 in the SAMR1 group, 3.88±1.46 in the SAMR1+Pb exposure group, 3.25±1.28 in the SAMP8 group, and 1.25±0.46 in the SAMP8+Pb exposure group; the numbers in the SAMR1+Pb exposure group, SAMP8 group, and SAMP8+Pb exposure group were low er than those in the SAMR1 group (P < 0.05); compared with the SAMP8 group and the SAMR1+Pb exposure group, the number in the SAMP8+Pb exposure group was also decreased (P < 0.05). The results of immunofluorescence technology showed that, compared with SAMR1 mice, the fluorescence intensity of APP increased by 79%, 53%, and 216% in the SAMR1+Pb exposure group, SAMP8 group, and SAMP8+Pb exposure group, respectively; compared with the SAMR1+Pb exposure group and the SAMP8 group, the fluorescence intensity of APP in the SAMP8+Pb exposure group increased by 76% and 107%, respectively (P < 0.05). Compared with the SAMR1 group, the cell ratios ofGFAP(+)/DAPI(+) and DCX(+)/DAPI(+) in SVZ of the SAMP8 group and the SAMP8+Pb exposure group were decreased; the ratios ofGFAP(+)/DAPI(+) and DCX(+)/DAPI (+) in SVZ of the SAMP8+Pb exposure group were 22% and 59% of the SAMP8 group, respectively. Compared with the SAMR1 group, the expression of BDNF and DCX mRNA in the SAMR1+Pb exposure group, SAMP8 group, and SAMP8+Pb exposure group were significantly decreased by real-time fluorescence quantitative PCR (P < 0.05). Compared with the SAMR1+Pb exposure group and the SAMP8 group, the expressions of BDNF mRNA in the SAMP8+Pb exposure group were decreased by 85% and 83%, respectively, and the expressions of DCX mRNA were decreased by 81% and 60%, respectively (P < 0.05). The expressions ofGFAP mRNA in the SAMP8 group and SAMP8+Pb exposure group were significantly lower than that in the SAMR1 group (P < 0.05); the expression ofGFAP mRNA in the SAMP8+Pb exposure group was decreased by 89% and 69% compared with the SAMR1+Pb group and the SAMP8 group, respectively (P < 0.05).
Conclusion Our findings show that lead exposure can aggravate the increasing of APP protein expression and the decreasing of BDNF mRNA expression, as well as result in less astrocytes in SVZ, prolonged escape latency, and reduced platform crossing counts, which indicate that lead exposure may accelerate the decline of learning and memory ability in senescence accelerated mice.
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