1.646000 四川 泸州,西南医科大学基础医学院:肿瘤医学研究所
2.400038 重庆,陆军军医大学(第三军医大学) 医学心理系军事认知心理学教研室
3.646000 四川 泸州,西南医科大学基础医学院:基础医学院生理学教研室
Received:06 February 2023,
Revised:2023-03-01,
Published:30 July 2023
移动端阅览
Jianghui LI, Dabing LI, Xianyu ZHU, et al. Lycopene improves social disorder and reduces hippocampal inflammation in BTBR mice[J]. Journal of Army Medical University, 2023, 45(14): 1483-1492.
Jianghui LI, Dabing LI, Xianyu ZHU, et al. Lycopene improves social disorder and reduces hippocampal inflammation in BTBR mice[J]. Journal of Army Medical University, 2023, 45(14): 1483-1492. DOI: 10.16016/j.2097-0927.202302024.
目的
2
研究番茄红素(Lycopene,Lyc)对BTBR T
+
Itpr3
tf
/ J(BTBR)自闭症模型小鼠海马组织中炎症水平、社交缺陷、认知障碍和重复刻板行为的影响。
方法
2
7~8周龄成年雄性健康C57BL/6(C57)与BTBR小鼠随机数字表法分为4组(
n
=8):C57+Veh组、C57+Lyc组、BTBR+Veh组、BTBR+Lyc组。C57+Lyc组和BTBR+Lyc组小鼠予以番茄红素(20 mg/kg)灌胃,1次/d,共7 d;C57+Veh组小鼠和BTBR+Veh组小鼠给予等体积的玉米油。给药7 d后开始三箱社交、雌雄交互、理毛、埋珠、开场实验、新物体识别、筑巢和Y迷宫等行为实验。结束后立即收取脑组织样本,进行RT-qPCR、Western blot实验。
结果
2
行为学结果显示:三箱社交实验中,BTBR+Veh组小鼠在陌生物体所在的箱体时间更多,表现出对陌生物体更偏好(
P
<
0.05);而Lyc治疗后小鼠表现出对陌生小鼠更偏好(
P
<
0.05)。理毛、埋珠实验中,BTBR+Veh组小鼠较C57+Veh组小鼠的重复刻板行为显著增多(
P
<
0.05),Lyc治疗后显著减少了BTBR小鼠的重复刻板行为(
P
<
0.05)。BTBR+Veh组小鼠较C57+Veh组小鼠海马组织中NLRP3炎症小体在mRNA和蛋白水平均显著增高(
P
<
0.05);白细胞介素-1β(interleukin-1β,IL-1β)、IL-18、IL-6、核因子κB (nuclear factor kappaB,NF-κB)、肿瘤坏死因子
α
(tumor necrosis factor-
α
,TNF-
α
) 在mRNA水平显著增高(
P
<
0.05);Lyc治疗后BTBR小鼠各炎症因子均显著降低(
P
<
0.05)。
结论
2
番茄红素治疗通过降低BTBR小鼠海马中NLRP3炎症小体的水平,改善BTBR小鼠三箱社交缺陷和重复刻板行为。
Objective
2
To investigate the effects of lycopene (Lyc) on hippocampal inflammation
social deficits and repetitive stereotyped behaviors in BTBR T
+
Itpr3tf/J autistic mice (BTBR
a mouse strain showing lower sociability as a model for autism spectrum disorder).
Methods
2
Adult male C57BL/6J (C57) and BTBR mice aged 7-8 weeks were randomly divided into (
n
=8): C57+Veh group
C57+Lyc group
BTBR+Veh group and BTBR+Lyc group. The mice from the C57+Lyc group and BTBR+Lyc group were given 20 mg/kg Lyc by gavage once a day for 7 d
and those of the C57+Veh group and BTBR+Veh mice were given equal volume of corn oil. Then three-chamber social test
male-female reciprocal social interactions
self-grooming
marble buying
open field test
object recognition test
nest building
and Y-maze test were conducted in these mice. Immediately after the behavioral tests
the
mice were sacrificed and their brain samples were harvested for RT-qPCR and Western blotting.
Results
2
Behavioral results showed that in the three-chamber social test
the mice of the BTBR+Veh group spent longer time in the chamber with the object
showing much curiosity about the object (
P
<
0.05)
while the mice after Lyc treatment showed a preference for strange mice (
P
<
0.05). In the self-grooming and marble burying behavior test
the BTBR+Veh group showed markedly increased repeated stereotyped behaviors than the C57+Veh group mice (
P
<
0.05)
which could be alleviated by Lyc treatment (
P
<
0.05). The hippocampal expression of NLRP3 at mRNA and protein levels (
P
<
0.05)
and the mRNA levels of IL-1β
IL-18
IL-6
NF-κB
and TNF-
α
were significantly increased in the BTBR+Veh group mice when compared with the C57+Veh group mice
and Lyc treatment obviously reversed above changes (
P
<
0.05).
Conclusion
2
Lyc treatment improves three-chamber social deficits and repetitive stereotyped behaviors in BTBR mice by reducing NLRP3 inflammasome in the hippocampus of BTBR mice.
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