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:
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.
Changes of PLCγ1/IP3R/CaMKⅡ protein expression and dendritic spine density in hippocampus of VPA-induced autistic young mice
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.
关键词
Keywords
references
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.
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.
Effects of clesmatine on myelination and neuronal activity during sleep in the hippocampus of adult APP/PS1 mice
Ovarian estrogen deficiency participates in the pathogenesis of Alzheimer’s disease by regulating hippocampal mitochondrial function and extracellular matrix remodeling
Effect of sleep deprivation on firing activity of hippocampal parvalbumin-expressing interneurons associated with trace eyeblink conditioning
Sodium valprovate upregulates miR-34a to inhibit Bcl-2 expression in human neuroblastoma SH-SY5Y cells in vitro
Changes in dentate gyrus neuronal activity during sleepwake cycle in mice
Related Author
YANG Ye
ZHANG Haibo
LIU Yanji
YAO Zhongxiang
HU Bo
ZHANG Xuan
ZHOU Maohu
MENG Zhaoyou
Related Institution
Experimental Center of Basic Medicine, College of Basic Medical Sciences, Army Medical University (Third Military Medical University)
Department of Physiology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University)
Department of Neurobiology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University)
Sports Medicine Center, First Affiliated Hospital, Army Medical University (Third Military Medical University)
Department of Neurology, Second Affiliated Hospital, Army Medical University (Third Military Medical University)