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400016 重庆, 重庆医科大学基础医学院神经科学研究中心
[ 杨戎,E-mail:1364262572@qq.com YANG Rong,E-mail:1364262572@qq.com
收稿:2020-02-26,
修回:2020-03-28,
纸质出版:2020-07-15
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赵雨, 王岩, 郑文霞, 等. VPA诱导的自闭症青年小鼠海马中PLCγ1/IP3R/CaMKⅡ蛋白表达和树突棘密度的变化[J]. 第三军医大学学报, 2020,42(13):1266-1272.
Yu ZHAO, Yan WANG, Wenxia ZHENG, et al. Changes of PLCγ1/IP3R/CaMKⅡ protein expression and dendritic spine density in hippocampus of VPA-induced autistic young mice[J]. Journal of Third Military Medical University, 2020, 42(13): 1266-1272.
赵雨, 王岩, 郑文霞, 等. VPA诱导的自闭症青年小鼠海马中PLCγ1/IP3R/CaMKⅡ蛋白表达和树突棘密度的变化[J]. 第三军医大学学报, 2020,42(13):1266-1272. DOI: 10.16016/j.1000-5404.202002189.
Yu ZHAO, Yan WANG, Wenxia ZHENG, et al. Changes of PLCγ1/IP3R/CaMKⅡ protein expression and dendritic spine density in hippocampus of VPA-induced autistic young mice[J]. Journal of Third Military Medical University, 2020, 42(13): 1266-1272. DOI: 10.16016/j.1000-5404.202002189.
目的
2
探讨丙戊酸钠(VPA)诱导的自闭症模型小鼠大脑海马区磷脂酶C-γ1(PLCγ1)/肌醇三磷酸受体(IP3R)/钙调蛋白依赖性激酶Ⅱ(CaMKⅡ)表达的改变和树突棘密度的异常。
方法
2
C57孕小鼠于孕10、12 d分别腹腔注射丙戊酸钠300 mg/kg或生理盐水,其仔鼠分别为自闭症谱系障碍模型鼠(VPA组)或正常对照鼠(CON组)。Western blot检测两组仔鼠大脑海马区PLCγ1、IP3R、CaMKⅡ和突触后致密物-95(PSD95)的表达水平。高尔基染色法检测2组仔鼠大脑海马区树突棘的变化。
结果
2
Western blot检测结果显示:与正常对照组相比,VPA组小鼠大脑海马区PLCγ1,IP3R,CaMKⅡ和PSD95的表达均下降(
P
<
0.01)。高尔基染色结果显示:与正常对照组相比,VPA组小鼠大脑海马区树突棘密度减少(
P
<
0.01)。
结论
2
VPA诱导的自闭症模型小鼠大脑海马区的PLCγ1/IP3R/CaMKⅡ表达下降,同时伴随着海马CA1区锥体神经元树突棘密度降低,PSD95的表达减少。
Objective
2
To investigate expression changes of phospholipase C-γ1 (PLCγ1)/inositol triphosphate receptor (IP3R)/calmodulin-dependent kinase Ⅱ (CaMKⅡ) and density of dendritic spine in the hippocampus of autism model mice induced by sodium valproate (VPA).
Methods
2
Pregnant C57 mouse was given intraperitoneal injection of 300 mg/kg VPA or same volume of normal saline at the 10th and 12th days of gestation. The offspring exposed to VPA or saline during gestation were identified as autism spectrum disorder mice (VPA group) or normal control mice (CON group). Western blotting was used to detect the expression levels of PLCγ1
IP3R
CaMKⅡ and post-synaptic dense-95 (PSD95) in the hippocampus of the 2 groups. Golgi staining was employed to observe the changes in dendritic spines in the hippocampus of the offspring mice.
Results
2
Western blotting showed that the expression levels of PLCγ1
IP3R
CaMKⅡ and PSD95 were decreased in the VPA group than the normal control group (
P
<
0.01). Golgi staining indicated that compared with the normal control group
the density of dendritic spines in the hippocampus of VPA mice was reduced (
P
<
0.01).
Conclusion
2
In the hippocampus of VPA induced autism mice
the expression of PLCγ1/IP3R/CaMKⅡ and PSD95 and the dendritic spine density of pyramidal neurons in hippocampal CA1 are all decreased compared with the normal control mice.
ROUBERTOUXP L, TORDJMAN S, CAUBIT X, et al . Construct validity and cross validity of a test battery modeling autism spectrum disorder (ASD) in mice[J ] . Behav Genet, 2020, 50(1): 26-40. DOI:10.1007/s10519-019-09970-x.
DE RUBEIS S, HE X, GOLDBERG A P, et al . Synaptic, transcriptional and chromatin genes disrupted in autism[J ] . Nature, 2014, 515(7526): 209-215. DOI:10.1038/nature13772.
YANG Y R, KANG D S, LEE C, et al . Primary phospholipase C and brain disorders[J ] . Adv Biol Regul, 2016, 61: 80-85. DOI:10.1016/j.jbior.2015.11.003.
JANG H J, SUH P G, LEE Y J, et al . PLCγ1: Potential arbitrator of cancer progression[J ] . Adv Biol Regul, 2018, 67: 179-189. DOI:10.1016/j.jbior.2017.11.003.
WANG M J, JIANG L, CHEN H S, et al . Levetiracetam protects against cognitive impairment of subthreshold convulsant discharge model rats by activating protein kinase C (PKC)-growth-associated protein 43 (GAP-43)-calmodulin-dependent protein kinase (CaMK) signal transduction pathway[J ] . Med Sci Monit, 2019, 25: 4627-4638. DOI:10.12659/MSM.913542.
KIM H Y, YANG Y R, HWANG H, et al . Deletion of PLCγ1 in GABAergic neurons increases seizure susceptibility in aged mice[J ] . Sci Rep, 2019, 9(1): 17761. DOI:10.1038/s41598-019-54477-4.
RINGSEVJEN H, UMBACH HANSEN H M, HUSSAIN S, et al . Presynaptic increase in IP3 receptor type 1 concentration in the early phase of hippocampal synaptic plasticity[J ] . Brain Res, 2019, 1706: 125-134. DOI:10.1016/j.brainres.2018.10.030.
郑文霞, 胡宇玲, 陈笛, 等.丙戊酸钠诱导小鼠自闭症模型的改良[J].南方医科大学学报, 2019, 39(6): 718-723.
ZHENG W X, HU Y L, CHEN D, et al . Improvement of a mouse model of valproic acid-induced autism[J ] . J South Med Univ, 2019, 39(6): 718-723.
TANG G M, GUDSNUK K, KUO S H, et al . Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits[J ] . Neuron, 2014, 83(5): 1131-1143. DOI:10.1016/j.neuron.2014.07.040.
MARKRAM K, RINALDI T, LA MENDOLA D, et al . Abnormal fear conditioning and amygdala processing in an animal model of autism[J ] . Neuropsychopharmacology, 2008, 33(4): 901-912. DOI:10.1038/sj.npp.1301453.
HARA Y, AGO Y, TARUTA A, et al . Risperidone and aripiprazole alleviate prenatal valproic acid-induced abnormalities in behaviors and dendritic spine density in mice[J ] . Psychopharmacology (Berl), 2017, 234(21): 3217-3228. DOI:10.1007/s00213-017-4703-9.
YAMAGUCHI H, HARA Y, AGO Y, et al . Environmental enrichment attenuates behavioral abnormalities in valproic acid-exposed autism model mice[J ] . Behav Brain Res, 2017, 333: 67-73. DOI:10.1016/j.bbr.2017.06.035.
YANG Y R, JUNG J H, KIM S J, et al . Forebrain-specific ablation of phospholipase Cγ1 causes manic-like behavior[J ] . Mol Psychiatry, 2017, 22(10): 1473-1482. DOI:10.1038/mp.2016.261.
SHIMOHAMA S, SUMIDA Y, FUJIMOTO S, et al . Differential expression of rat brain phospholipase C isozymes in development and aging[J ] . Biochem Biophys Res Commun, 1998, 243(1): 210-216. DOI:10.1006/bbrc.1998.8090.
GIRALT A, RODRIGO T, MARTÍN E D, et al . Brain-derived neurotrophic factor modulates the severity of cognitive alterations induced by mutant huntingtin: involvement of phospholipase C gamma activity and glutamate receptor expression[J ] . Neuroscience, 2009, 158(4): 123 4-1250. DOI:10.1016/j.neuroscience.2008.11.024.
SHARPA H, NUCIFORA F C Jr, BLONDEL O, et al . Differential cellular expression of isoforms of inositol 1, 4, 5-triphosphate receptors in neurons and Glia in brain[J ] . J Comp Neurol, 1999, 406(2): 207-220.
TAKEMOTO-KIMURA S, SUZUKI K, HORIGANE S I, et al . Calmodulin kinases: essential regulators in health and disease[J ] . J Neurochem, 2017, 141(6): 808-818. DOI:10.1111/jnc.14020.
XU J, LIU Z A, PEI D S, et al . Calcium/calmodulin-dependent kinase II facilitated GluR6 subunit serine phosphorylation through GluR6-PSD95-CaMKII signaling module assembly in cerebral ischemia injury[J ] . Brain Res, 2010, 1366: 197-203. DOI:10.1016/j.brainres.2010.09.087.
PENZES P, CAHILL M E, JONES K A, et al . Convergent CaMK and RacGEF signals control dendritic structure and function[J ] . Trends Cell Biol, 2008, 18(9): 405-413. DOI:10.1016/j.tcb.2008.07.002.
SCHMUNK G, BOUBION B J, SMITH I F, et al . Shared functional defect in IP3 R-mediated calcium signaling in diverse monogenic autism syndromes[J ] . Transl Psych iatry, 2015, 5: e643. DOI:10.1038/tp.2015.123.
KÜRY S, VAN WOERDEN G M, BESNARD T, et al . De novo mutations in protein kinase genes CAMK2A and CAMK2B cause intellectual disability[J ] . Am J Hum Genet, 2017, 101(5): 768-788. DOI:10.1016/j.ajhg.2017.10.003.
COLEY A A, GAO W J. PSD95: a synaptic protein implicated in schizophrenia or autism?[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2018, 82: 187-194. DOI:10.1016/j.pnpbp.2017.11.016.
MARDONES M D, JORQUERA P V, HERRERA-SOTO A, et al . PSD95 regulates morphological development of adult-born granule neurons in the mouse Hippocampus[J ] . J Chem Neuroanat, 2019, 98: 117-123. DOI:10.1016/j.jchemneu.2019.04.009.
DE RUBEIS S, HE X, GOLDBERG A P, et al . Synaptic, transcriptional and chromatin genes disrupted in autism[J ] . Nature, 2014, 515(7526): 209-215. DOI:10.1038/nature13772.
FEYDER M, KARLSSON R M, MATHUR P, et al . Association of mouse Dlg4 (PSD-95) gene deletion and human DLG4 gene variation with phenotypes relevant to autism spectrum disorders and Williams' syndrome[J ] . Am J Psychiatry, 2010, 167(12) : 1508-1517. DOI:10.1176/appi.ajp.2010.10040484.
KARAYANNIS T, AU E, PATEL J C, et al . Cntnap4 differentially contributes to GABAergic and dopaminergic synaptic transmission[J ] . Nature, 2014, 511(7508): 236-240. DOI:10.1038/nature13248.
GOVEK E E, NEWEY S E, VAN AELST L. The role of the Rho GTPases in neuronal development[J]. Genes Dev, 2005, 19(1): 1-49. DOI:10.1101/gad.1256405.
SAITOH O, COURCHESNE E, EGAAS B, et al . Cross-sectional area of the posterior Hippocampus in autistic patients with cerebellar and corpus callosum abnormalities[J ] . Neurology, 1995, 45(2): 317-324. DOI:10.1212/wnl.45.2.317.
MORIMURA N, YASUDA H, YAMAGUCHI K, et al . Autism-like behaviours and enhanced memory formation and synaptic plasticity in Lrfn2/SALM1-deficient mice[J ] . Nat Commun, 2017, 8: 15800. DOI:10.1038/ncomms15800.
SHEN W J, KILANDER M B C, BRIDI M S, et al . Tomosyn regulates the small RhoA GTPase to control the dendritic stability of neurons and the surface expression of AMPA receptors[J ] . J Neurosci Res, 2020: 1-19. DOI:10.1002/jnr.24608.
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