| Objective:The effect of neural development in offspring mice and the may mechanism during pregnancy exposure to nano alumina. Methods:Female ICR mice and the male ICR mice, two months old. Both of them were 25-30 g, all the female mice were randomly divided into four groups: control group(saline), 10μm alumina group(50 mg/ml), 50 nm alumina group(50 mg/ml), 13 nm alumina group(50 mg/ml). Each group have 10 mice. Female mice were given for 3 /d nasal drip, 50mg/kg for 10 day before mating. Female mice and male mice were mated overnight 1:1, remove the male mice when found the vaginal suppository, then female mice continue exposed to the offspring born.I. The offspring of which born from 5 female mice were randomly selected to detective the index of physiological: birth weight(born after 1, 4, 7, 14, 28 day), ears opening(recorded the first days after birth), teething(recorded after ninth days), eyes opening(recorded after tenth days); reflection and sensory function test: the plane righting reflex(recorded twice after fourth days and seventh days), cliff avoidance reflex(recorded twice after fourth days and seventh days); endurance: forelimb hanging test(recorded twice after twelfth days and fourteenth days); open field test when the mice are 29 days after birth; Morris water maze navigation experiment:(postnatal day 30, 5 days), the experimental of space exploration(the beginning of the end of navigation experiment).II. The remaining 5 mice’s offspring were weighed at postnatal day. Use Graphite Furnace Atomic Absorption Spectrometry determination the aluminum content in brain o tissue of offspring in each group, the level of oxidative stress by reagent kit(malondialdehyde, superoxide dismutase) detection the brain cholinergic neurotransmitter(acetylcholine transferase and acetylcholinesterase), to explore the possible mechanism of nano alumina induced neural developmental toxicity in the offspring mice. Results:I. The results of behavioral test show that: compared with the solvent control group the other groups’ body weight of the offspring were decreased(P<0.01); compared with the solvent control group, 13 nm alumina group and 50 nm alumina group are delay and statistically significant differences in ear opening, teething and eye opening(F ear opening=11.708; F teething=32.635; F eye opening=15.143; P<0.01); whether PND4 or PND7 plane righting index showed no significant difference in statistics(4dχ2=2.856, 7d χ2=1.644, P>0.05). But the cliff avoidance experimental compliance rate had significant difference(4d χ2=4.397, 7d χ2=6.12, P<0.05, P<0.01), compared with the control group, the rest groups’ cliff avoidance rate were decreased in different degree.Compared with the solvent control group, 50 nm group, 13 nm alumina group’s forelimb hanging test time is reduced, and the difference was statistically significant(F12=6.513, F14=4.814, P<0.01).In the place navigation test, there was not statistically significant in escape latency between each other at first three days, compared with the solvent control group the other groups’ fourth day escape latency are increased, the fifth day’ escape latency has statistically increased between 13nm/50 nm alumina groups and the other two groups. The target area residence time are no significant difference(F=0.860, P=0.497). However, compared with the solvent control group the other groups’ number of crossing the platform show significant difference(F=12.135, P<0.01).Open field test center time was not statistically significant(F=0.375, P=0.945); but compared with the solvent control group 13 nm alumina group central lattice distance increased(F=1.730, P<0.01), the control group in the rearing and grooming show statistically significant compared to the other groups(F=3.510, P<0.01. F=2.172, P<0.01).II. Mice brain aluminum detected showed that: compared with other groups of female mice body weight have not statistically significant(P>0.05); mice the first day of birth weight 13 nm alumina group 50 nm group compared with the solvent control group and the 10μm alumina group were significantly different(F=27.359, P<0.01); but the 13 nm alumina group was not statistically different compared to 50 nm alumina group; compared with the solvent control group, 13 nm group, 50 nm alumina group and 10μm alumina group’s brain aluminum levels have increased significantly, and has statistical significance(F=103.571, P<0.01); compared with the 10μm alumina group, 50 nm alumina group and 13 nm alumina group’s brain aluminum content was significantly increased, and there was statistical significance; 13 nm alumina group’s aluminum content in the brain of neonatal mice were increased significantly compared to 50 nm alumina group, and the there was statistical significance.III. The results of each group neurodevelopmental toxicity mechanism pups show: oxidative stress in brain tissue by detecting pups show that compared with the control group and the 10μm alumina group, there was a significant difference in 13 nm and 50 nm alumina group(F=7.839, P<0.05), but there was no statistically significant difference between 13 nm alumina group and 50 nm alumina group; Offspring brain tissue free radical scavenging capacity indicators show compared with 50 nm alumina group, solvent control group and 10μm alumina group, 13 nm alumina group significantly decreased(F=9.733, P<0.05), but there was no statistically significant difference between 10μm alumina group and 50 nm alumina group; Results of cholinergic neurotransmitter show that compared with 50 nm alumina group, solvent control group and 10 um alumina group, 13 nm alumina group’s Ch AT vitality significantly decreased(F=134.266, P<0.01), but there was no significant difference between 10 um alumina group and 50 nm alumina group; Compared with 50 nm alumina group, solvent control group and 10μm alumina group, 13 nm alumina group’s TCh E vitality significantly decreased(F=19.520, P<0.01), but there was no statistically significant difference between 10μm alumina group and solvent control group. Conclusions:Nano-alumina can inhibit the offspring’s physiological development and the early behavioral development during the pregnancy exposed; It can also decrease the pups’ learning and memory and the ability to adapt to novel environments; With the particle size decreased nano-alumina’s developmental toxicity increased. Nano-alumina may across the placental barrier and blood-brain barrier to enter the pups’ brain during pregnancy exposed, and with nano-alumina’s particle size decreased the aggregation in pups’ brain increased. The possible mechanisms of nano-alumina can causes neurodevelopmental toxicity in offspring during pregnancy exposure is nano-alumina caused the oxidant / antioxidant imbalance in pups’ brain tissue and caused the changes of cholinergic neurotransmitter of pups, and it also have particle size effects exist. |
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