Protective effect of thymosin alpha-1 on postnatal systemic inflammation induced learning and memory impairment in mice
10.3760/cma.j.issn.1671-8925.2017.02.003
- VernacularTitle:胸腺肽a1对小鼠新生期感染所致学习记忆障碍的影响
- Author:
Ge WANG
1
;
Wenfu YU
;
Xiao WANG
;
Fen HE
;
Juntao ZOU
Author Information
1. 衢州职业技术学院医学院
- Keywords:
Infectious disease;
Thymosin alpha-l;
Learning and memory ability;
Brain-derived neurotrophic factor;
Nerve growth factor;
Toll-like receptor 4;
Nuclear factor-κB
- From:
Chinese Journal of Neuromedicine
2017;16(2):121-126
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect ofthymosin alpha-1 (Ta1) on postnatal systemic inflammation-induced learning and memory impairment in mice and their relevant mechanism.Methods (1) Twenty-four neonatal C57BL/6 mice were randomly assigned into normal saline group,lipopolysaccharide (LPS,0.3 mg/kg) group,LPS (0.6 mg/kg) group,and LPS (0.9 mg/kg) group.And the animals were intraperitoneally injected with different doses of LPS or equal volume of saline for 5 days.The variations of body weight,liver weight relative to the body and tumor necrosis factor-α (TNF-α) level in serum and brain tissues were observed to determine the appropriate dose of LPS for simulating neonatal clinical infection.(2) A total of 60 newborn mice were randomly divided into three groups:control group,LPS group and Ta1 treatment group;mice in each group were continuously injected with equal volume saline,LPS (0.6 mg/kg) and Tal (0.4 mg/kg)+LPS (0.6 mg/kg) for 5 days.On day 28 and on day 56,Morris water maze was used to measure the spatial learning and memory abilities of mice;the concentrations of TNF-α,interleukin-1β (IL-1β),brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus were examined by ELISA,and the expressions of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) were measured by Western blotting.Results (1) As compared with the normal saline group,the mice in the LPS group (0.6 mg/kg) had significantly slower growth ([2.23±0.22] g vs.[1.18±0.21] g),increased relative liver weight to the body (0.052±0.004 vs.0.072±0.007) and increased TNF-α levels in serum and brain tissues ([62.01±3.32] pg/mL vs.[151.06± 14.51] pg/mL;[186.03±13.24] pg/mL vs.[298.71±41.61] pg/mL,P＜0.05).(2) As compared with the LPS group,Tal treatment group had significantly shortened average escape latency in place navigation test,prolonged active time in spatial probe test,statistically decreased hippocampal TNF-α,IL-1β,TLR4 and NF-κB levels ([73.32±5.18] pg/mL vs.[58.61 ±4.03] pg/mL;[99.15±8.30] pg/mL vs.[75.56±6.13] pg/mL;2.32±0.29 vs.1.71±0.26;1.77±0.24 vs.1.26±0.14) and significantly increased BDNF and NGF levels ([1.33±0.12] pg/mL vs.[1.69±0.25] pg/mL;[41.45±3.47] pg/mL vs.[50.38±5.02] pg/mL,P＜0.05).Conclusion Tal improves learning and memory functions and alleviates neuro-inflammation in postnatal infection of mice,and the underlying mechanism probably involves in inhibiting TLR4/NF-κB signaling pathway activation and increasing neurotrophic factors.
