RESUMO
<p><b>OBJECTIVE</b>To study influence of lanthanum chloride (LaCl(3)) on the expression of immediate early genes (IEGs) including c-jun, early growth response gene 1 (Egr1) and activity-regulated cytoskeletal gene (Arc) in the hippocampus of rats, and discuss the mechanism of LaCl(3) undermining learning and memory capability.</p><p><b>METHODS</b>Forty female Wistar adult rats were divided into control group, low LaCl(3)-contaminated group (0.25%), medium LaCl(3)-contaminated group (0.50%), and high LaCl(3)-contaminated group (1.00%) by randomized design. Each group had ten female rats along with five male rats and mated by the ratio of 2:1. The amounts of pups in the above four groups were 80, 83, 78 and 75 separately. The pups in respective group were La-dyed by lactation, and then the pups in LaCl(3)-contaminated groups drank 0.25%, 0.50% and 1.00% LaCl(3) separately for one month. Learning and memory capability of pups were measured in jumping stairs experiment. Hippocampal lanthanum content was determined by inductively coupled plasma mass spectrometry (ICP-MS). Hippocampal c-jun, Egr1 and Arc mRNA expression was detected by RT-PCR, and corresponding protein expression was measured by Western blotting method.</p><p><b>RESULTS</b>In the jumping stairs experiment, pups in 0.25%, 0.50% and 1.00% LaCl(3)-contaminated groups respectively made (1.75 ± 0.71), (2.38 ± 0.92) and (3.00 ± 0.76) mistakes; significantly higher than control group (1.25 ± 0.46) (q values were 4.386, 6.793, P < 0.05). However, the incubation period of 0.25%, 0.50% and 1.00% LaCl(3)-contaminated groups were (174.13 ± 33.72), (139.25 ± 45.83) and (75.50 ± 18.56) respectively, which were all significantly lower than that of control group (206.75 ± 20.47) (q values were 2.958, 6.121, 11.902, P < 0.05). Hippocampal c-jun mRNA expression were (0.89 ± 0.08), (0.77 ± 0.12), (0.58 ± 0.14) and (0.29 ± 0.10); while the c-jun protein expression were (0.72 ± 0.13), (0.64 ± 0.11), (0.43 ± 0.11) and (0.31 ± 0.14), and the Egr1 mRNA expression were (0.78 ± 0.09), (0.61 ± 0.13), (0.53 ± 0.10) and (0.22 ± 0.08), Egr1 protein expression were (0.65 ± 0.18), (0.40 ± 0.15), (0.32 ± 0.13) and (0.14 ± 0.09) in 0.25%, 0.50% and 1.00% LaCl(3)-contaminated groups; and all of which presented a dose-effect relationship that the correlation coefficients of these parameters with dose were -0.900 (t = 11.309, P = 0.000), -0.969 (t = 7.058, P = 0.000), -0.898 (t = 11.179, P = 0.000) and -0.962 (t = 6.739, P = 0.000).</p><p><b>CONCLUSION</b>LaCl(3) undermines the learning and memory capability of rats, which is possibly related to lower expression of c-jun and Egr1 gene and protein induced by lanthanum in hippocampus.</p>
Assuntos
Animais , Feminino , Masculino , Ratos , Proteína 1 de Resposta de Crescimento Precoce , Metabolismo , Expressão Gênica , Genes Precoces , Genética , Hipocampo , Metabolismo , Lantânio , Farmacologia , Aprendizagem , Memória , Proteínas Proto-Oncogênicas c-jun , Metabolismo , Ratos WistarRESUMO
<p><b>OBJECTIVE</b>To investigate the effects of aluminum on learning and memory and the expression of N-methyl-D-aspartic acid receptor (NMDAR) of hippocampus in offspring from female rats exposed to Al in the pregnancy or lactation, and to explore the mechanism of toxic effects of Al on central nervous system (CNS) during development.</p><p><b>METHODS</b>The pregnant Wistar rats were randomly divided into 3 groups based on their body weight, i.e. control group was exposed to distilled water, low exposure group (0.2%AlCl3) and high exposure group (0.4%AlCl3) were exposed orally to AlCl3 in pregnancy and lactation for 6 weeks, 10 rats each group. Aluminum content in blood and brains was determined by atomic absorption spectrophotometry (AAS). Platform experiment was used to detect the abilities of learning and memory. The expression levels of NMDARs were detected by western blot assay.</p><p><b>RESULTS</b>The Al content in blood and brains of rats in exposure groups increased significantly with Al dose, as compared with the control group (P < 0.05). In platform experiment, the incubation periods of rats in low and high exposure groups were (202.71 ± 81.99) and (19.67 ± 8.44) s respectively, which were significantly lower than that [(300.00 ± 0.00) s] in control group (P < 0.01), but the mistake times of rats in low and high exposure groups were 1.43 ± 0.85 and 2.47 ± 0.99 respectively, which were significantly higher than that (0.00 ± 0.00) in control group (P < 0.01). The Al exposure could change the proportion of NMDAR subtypes, the expression levels of NR1 and NR2B in hippocampus of newborn rats in low and high exposure groups were 25.22 ± 0.68, 81.23 ± 15.37 and 24.75 ± 0.71, 56.63 ± 7.82, respectively, which were significantly lower than those (31.69 ± 3.44, 107.61 ± 9.05) in control group (P < 0.05).</p><p><b>CONCLUSION</b>Aluminum exposure in pregnancy and lactation could reduce the abilities of learning and memory in newborn rats, and change the proportion of NMDAR subtypes. The reduced NR1 and NR2B expression levels may be one of important mechanisms to influence the abilities of learning and memory in offspring.</p>
Assuntos
Animais , Feminino , Masculino , Gravidez , Ratos , Alumínio , Toxicidade , Hipocampo , Metabolismo , Aprendizagem em Labirinto , Efeitos Tardios da Exposição Pré-Natal , Metabolismo , Ratos Wistar , Receptores de N-Metil-D-Aspartato , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To estimate the effect of aluminum on hippocampal intracellular Ca²+ concentration and expression of phospholipase C (PLC) and NMDA receptor α (NMDARα) genes in hippocampus as well as the neural behaviors in weaning rats through subchronic exposure in order to explore the mechanism which aluminum impaired the ability of learning and memory of central nervous system development.</p><p><b>METHODS</b>Weaning Wistar rats were randomly divided into four groups based on their body weight. Aluminium chloride was administered by water at the doses of 0.2%, 0.4% and 0.6% (m/v) for 90 days. Platform experiment was used to detect the activity of learning and memory. Fura-2/AM calcium ions fluorescence indicator was used to measure Ca²+ concentration in hippocampal neurons. Western blot method was used to detect the expressions of PLC and NMDARα genes.</p><p><b>RESULTS</b>The incubation of rats in platform experiment [(232.20 ± 57.45), (35.00 ± 9.37), (16.10 ± 5.57) s] shortened while increase of mistake times (1.10 ± 0.74, 2.20 ± 0.92, 3.40 ± 1.51) was significantly associated with the dose of aluminum (P < 0.01). The Ca(2+) concentration decreased significantly in the rats of aluminum exposed groups (P < 0.01). The expression of PLC and NMDARα in aluminum exposed groups (0.30 ± 0.06, 0.18 ± 0.04, 0.16 ± 0.03; 0.38 ± 0.03, 0.32 ± 0.02, 0.25 ± 0.02) decreased significantly compared with that in the control group (0.47 ± 0.07, 0.48 ± 0.04) (P < 0.01) and there was a dose-effect relationship in the NMDARα expression.</p><p><b>CONCLUSION</b>Subchronic exposure of aluminium could impair the ability of learning and memory in rats during development, inhibit the expression of NMDARα and PLC and reduce Ca²+ concentration, suggesting that the disorder of Ca²+ signaling system might be one of mechanisms of aluminium damaging the ability of learning and memory.</p>