[Impairment of the hypothalamus and striatum of rats following lead exposure].

ABSTRACT

OBJECTIVE: To investigate the impairment of lead exposure on rat hypothalamus and striatum. METHODS: Forty-five healthy SPF male SD rats were randomly divided into three groups, control group( double distilled water), low( 60 mg/kg BW) and high dose( 120 mg/kg BW) groups. The rats were treated with lead acelate water solution in lead exposure group by gavage for 9 weeks. Open-field test was used to detect behavioral changes of the rats. The lead content of hypothalamus and striatum was determined by inductively coupled plasma mass spectrometry( ICP-MS). The mRNA expressions of toll-like receptor 4( TLR4), nuclear transcription factor kappa B( NF-κB), tumor necrosis factors alpha( TNF-α), interleukin-1( IL-1ß) and 8-oxoguanine DNA glycosylase( OGG1) were measured by real-time PCR. Enzyme linked immunosorbent assay( ELISA) was applied to detect the protein content of TLR4, NF-κB, TNF-α, IL-1ß and 8-hydroxy-2-deoxyguanosine( 8-OHd G). RESULTS: There were no significant differences in terms of body weight among three groups of rats. Compared with the control group, total movement distance, the total number of lattice and the distance of the central region in low and high lead exposure group were significantly decreased( P < 0. 05). The lead contents in hypothalamus and striatum of rats of low and high lead exposure group were( 60. 10 ± 6. 71), ( 71. 20 ± 11. 24), ( 44. 07 ± 9. 63)and( 66. 67 ± 8. 78) µg/g, respectively, higher than those in the control group(( 33. 77± 8. 19), ( 25. 75 ± 6. 33) µg/g)( P < 0. 05). While compared with the control group, the mRNA expression of NF-κB and OGG1 of the low and high lead exposure group were( 3. 47 ± 0. 15), ( 1. 43 ± 0. 16) and( 0. 67 ± 0. 13), ( 0. 57 ± 0. 19) folds in hypothalamus, there were marked differences in the mRNA expression of TLR4 and NF-κB between low and high lead group. The NF-κB, TNF-α, IL-1ß protein contents in hypothalamus of the low lead exposure group were( 5. 85 ± 1. 10), ( 56. 15 ± 6. 96) and( 1. 18 ± 0. 20) ng/g, respectively higher than those in control group(( 3. 03 ± 0. 71), ( 49. 25 ± 7. 21) and( 0. 86 ± 0. 11) ng/g)( P < 0. 05). The TLR4, NF-κB, TNF-α, IL-1ß protein contents in hypothalamus of the high lead exposure group were( 0. 67 ± 0. 12), ( 4. 74 ± 0. 68), ( 69. 73 ± 9. 61) and( 1. 43 ± 0. 29) ng/g, respectively, higher than those in control group. There were marked differences in the protein contents of TLR4 and TNF-α significant between low and high lead group in hypothalamus. The mRNA expression of TLR4, NF-κB, IL-1ß in the striatum of rats in the high lead exposure group were significantly higher than those in control group( P < 0. 05). The TLR4, NF-κB, TNF-α, IL-1ß, 8-OHd G protein contents of the high lead exposure group were( 0. 33 ±0. 02) ng/g, ( 4. 66 ± 0. 51), ( 82. 63 ± 7. 99), ( 1. 92 ± 0. 35) and( 1. 21 ± 0. 14) ng/g, respectively higher than those in control group( P < 0. 05), NF-κB protein content of the high lead exposure group was higher than that in low lead exposure group( P < 0. 05). CONCLUSION: Lead exposure does result in the impairment of hypothalamus and striatum, indicating that inflammation and oxidative damage might be involved in this process.