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1.
Chinese Journal of Applied Clinical Pediatrics ; (24): 140-145, 2023.
Article in Chinese | WPRIM | ID: wpr-990003

ABSTRACT

Objective:To explore the effects of the compound ICG-001 on autism-like behaviors and the morphological development of dendritic spines in hippocampal pyramidal neurons of rats.Methods:Healthy Wistar rats were mated.The offspring were divided into the saline-treated group, ICG-001 control group, Sodium valproate (VPA) group and ICG-001 treatment group by using the random number table method.Each group had 12 rats.Social interaction, repetitive, compulsive and anxiety-like behaviors in rodents were assessed by three-chambered social approach, marble burying, open-field and elevated plus maze tests.The number of neuronal nuclei (NeuN)-positive neurons in the hippocampal CA1 region was calculated by the immunofluorescence method.Golgi staining was carried out to detect the density and morphological changes of dendritic spines in hippocampal pyramidal neurons of rats.The expression of phosphorylated LIM kinase 1(LIMK1), phosphorylated actin binding protein(Cofilin), fibros actin (F-actin) and developmentally-regulated brain protein A (Drebrin A) was examined by Western blot.The univariate analysis was made to examine whether the difference was statistically significant, and the data between groups were compared by the Tukey method. Results:(1) In the three-chambered social approach test, the rats in the saline-treated group, ICG-001 control group, VPA group and ICG-001 treatment group spent (219.42±5.38) s, (218.67±10.12) s, (126.58±5.02) s, and (218.58±6.63) s in the chamber, respectively.The corresponding preference score of the said 4 groups were 0.43±0.05, 0.43±0.04, 0.22±0.01 and 0.42±0.04, respectively.Compared with the VPA group, the ICG-001 treatment group spent longer time in the chamber and had a higher preference score (all P<0.05). (2) In the marble burying experiment, the number of marbles buried in said 4 groups were 9.13±0.52, 9.08±0.64, 15.13±0.82 and 9.42±0.86, respectively.ICG-001-treated rats buried markedly less marbles than VPA-exposed rats ( P<0.05). (3) In the open-field test, the rats in the said 4 groups spent (82.33±1.83) s, (81.32±4.19) s, (45.51±3.02) s and (81.44±3.19) s in the center area, respectively.Administration of ICG-001 significantly increased the time that VPA-exposed rats spent in the center area ( P<0.05). (4)In the elevated plus maze trial, the rats in the said 4 groups spent (107.75±7.23) s, (106.08±7.50) s, (63.42±1.91) s and (106.67±7.07) s in open arms, respectively.ICG-001 treatment notably increased the time that VPA-exposed rats spent in open arms ( P<0.05). (5) Immunofluorescence analysis results revealed that the number of NeuN-positive cells in the hippocampal CA1 region of said 4 groups was (41.83±1.17)×10 4/μm 2, (41.00±0.77)×10 4/μm 2, (27.17±0.95)×10 4/μm 2 and (40.00±0.90)×10 4/μm 2, respectively.ICG-001 treatment normalized the alteration in the number of NeuN-containing neurons in VPA-exposed rats ( P<0.05). (6) Golgi staining showed that the density of dendritic spines in hippocampal CA1 pyramidal neurons of said 4 groups was (0.74±0.04)/μm, (0.73±0.03)/μm, (0.49±0.03)/μm and (0.70±0.02) /μm, respectively.Of all types of dendritic spines, mushroom spines accounted for (0.49±0.02)%, (0.49±0.02)%, (0.33±0.02)% and (0.43±0.02) % in said 4 groups.Thin spines accounted for (0.27±0.02)%, (0.26±0.02)%, (0.34±0.01)% and (0.26±0.01) % in said 4 groups, respectively.Compared with the VPA group, the ICG-001 treatment group showed a significant increase in the density of dendritic spines in hippocampal CA1 pyramidal neurons ( P<0.05). After ICG-001 treatment, the number of mushroom spines greatly increased and the number of thin spines sharply decreased in VPA-exposed rats (all P<0.05). (7) According to Western blot test results, the phosphorylated LIMK1/LIMK1 ratio of the hippocampus in said 4 groups were 100.33±2.30, 99.34±2.28, 57.76±4.10 and 99.13±1.90, respectively.The phosphorylated Cofilin /Cofilin ratio were 100.18±2.43, 100.18±1.70, 57.12±1.88 and 99.53±1.69, respectively.The F-actin/globular actin(G-actin) ratio were 100.07±0.86, 99.99±1.72, 51.19±1.23 and 99.28±3.17, respectively.The expression level of Drebrin A were 100.79±1.19, 100.12±2.04, 52.86±3.26 and 99.97±2.44, respectively.Administration of ICG-001 effectively prevented the decrease of phosphorylated LIMK1, phosphorylated Cofilin, F-actin and Drebrin A in the hippocampus of VPA-exposed rats (all P<0.05). Conclusions:ICG-001 regulates the LIMK1/Cofilin signaling pathway, promotes the generation of F-actin, increases the expression of Drebrin A, and thereby alleviates autistic-associated symptoms.

2.
Chinese Journal of Rehabilitation Theory and Practice ; (12): 23-28, 2018.
Article in Chinese | WPRIM | ID: wpr-702433

ABSTRACT

@#Objective To observe the effects of triptolide on drebrin and cofilin expression in the hippocampus of rats with Alzheim-er's disease (AD). Methods Sixty male Sprague-Dawley rats were equally divided into control group, model group and triptolide-treated group with 20 cases in each group. The AD model was established with unilateral injection of beta amyloid 1-40 (Aβ1- 40) into hippocampus in rats. The control group was established with unilateral injection of normal saline with the same volume into hippocampus in rats. The triptolide-treated group was administered triptolide intraperi-toneally, 0.4 mg/kg, once a day, for 15 days after modeling. Spine density of hippocampal neurons was assayed by Golgi staining. Drebrin and cofilin expression of hippocampal neurons was assayed by immunohistochemical staining and reverse transcription polymerase chain reaction (RT-PCR). Results The spine density of hippocampal neurons was higher in the triptolide-treated group than in the model group (P<0.05). The average optical density of drebrin was higher in the triptolide-treated group than in the the model group (P<0.01), while the cell number and average optical density of cofilin were lower (P<0.05). The drebrin mRNA expression was higher in the triptolide-treated group than in the model group (P<0.05), and the cofilin mRNA expression was lower (P<0.01). Conclusion Triptolide may delay the degeneration of dendritic spines in hippocampal neurons of AD rats by regulating the expression of drebrin and cofilin.

3.
Chinese Pharmacological Bulletin ; (12)2003.
Article in Chinese | WPRIM | ID: wpr-568100

ABSTRACT

As the neuron-specific actin binding protein,Drebrin ( developmentally regulated brain protein) can affect spiny and synaptic morphology and function by changing the property of cytoskeleton,and modulate synaptic plasticity. Neural excitability regulates expression and activitiy of Drebrin through a variety of signaling molecules,making Drebrin' s function correlated with that of neurons. Under pathological conditions,the abnormal Drebrin affects synaptic plasticity,which leads to different degrees of cognitive dysfunction,and it is closely relates to the progress of cognitive dysfunction. Extensive studies of physiological and pathological functions of Drebrin in overall and molecular ways will not only contribute to a thorough understanding of cognitive dysfunction,but also develop the new target of therapeutics for cognitive dysfunction.

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