RESUMEN
Objective:To investigate the effect of ginkgo biloba extract (GBE) on oxidative stress in medial prefrontal cortex and excitatory/inhibitory balance of pyramidal neurons in chronic unpredictable mild stress (CUMS)-induced depressive model mice.Methods:Totally 48 SPF grade 7-week-old male C57BL/6J mice were divided into 4 groups according to random number table method: control+ saline group (CTRL+ Veh), control+ GBE group (CTRL+ GBE), model+ saline group (CUMS+ Veh), model+ GBE group (CUMS+ GBE), with 12 mice in each group.Mice in CUMS+ Veh group and CUMS+ GBE group were established by CUMS method, and mice in CTRL+ GBE group and CUMS+ GBE group were intraperitoneally injected with GBE (70 mg/kg) once a day, and mice in CTRL+ Veh group and CUMS+ Veh group were injected intraperitoneally with 0.9% sodium chloride solution.Then, the sucrose preference test, forced swimming test (FST) and tail suspension test (TST) were performed to evaluate the depressive-like behavior of mice, and open field test (OFT) was performed to evaluate the autonomous locomotion and exploration ability and anxiety-like behavior.The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in mPFC were determined by ELISA.Spontaneous excitatory postsynaptic currents (sEPSC) and spontaneous inhibitory postsynaptic currents (sIPSC) were detected by whole-cell recording.SPSS 23.0 was used for data analysis and two-factor analysis of variance(whether to get GBE, whether to mold, show as GBE×CUMS) was used for statistical analysis.Results:(1) Behavioral results: the the time spent in center and total distance of OFT and sugar preference rate of the four groups of mice were compared, and the interaction of GBE×CUMS was significant( F=24.90, 4.82, 3.91, all P<0.05). The results of simple effect analysis showed that the time spent in center ((47.15±3.58) s), the total distance((19.33±0.86) m) and the sugar preference rate((59.11±8.79)%) of the mice in CUMS+ Veh group were lower than those in the CTRL+ Veh group((61.55±2.49) s, (23.24±1.21) m, (84.02±7.45) %) (all P<0.01), and the above indexes in CUMS+ GBE group ((56.51±3.53) s, (20.75±1.31) m, (70.80±11.79)%) were higher than those in CUMS+ Veh group (all P<0.05). In the immobility time of FST and TST of mice in the 4 groups, the interaction of GBE×CUMS were significant( F=85.53, 83.39, both P<0.01). The immobility time of FST and TST in CUMS+ Veh group were higher than those in CTRL+ Veh group (both P<0.01 ), and the above indexes in CUMS+ GBE group were lower than CUMS+ Veh group(both P<0.05). (2)The results of ELISA showed that the interaction of GBE×CUMS of SOD level of mice in the 4 groups was not significant ( F=3.52, P=0.07), but the main effects of GBE factor and CUMS factor were both significant ( F=4.69, 46.93, both P<0.05). The interaction of GBE×CUMS of MDA level was significant( F=16.61, P<0.01). The level of SOD in the CUMS+ Veh group was lower than that in the CTRL+ Veh group ( P<0.01), and the level of SOD in the CUMS+ GBE group was higher than that in the CUMS+ Veh group ( P<0.05). The level of MDA in the CUMS+ Veh group was higher than that of the CTRL+ Veh group ( P<0.01), and the level of MDA in CUMS+ GBE group was lower than that of the CUMS+ Veh group ( P<0.01). (3) The results of whole-cell recording showed that the interaction of GBE×CUMS of frequency and quantification of sEPSC in the four groups were significant ( F=5.45, 6.94, both P<0.05). The sEPSC frequency and quantification in the CUMS+ Veh group were lower than those in the CTRL+ Veh group (both P<0.01), and the sEPSC frequency and quantification in CUMS+ GBE group were higher than those of CUMS+ Veh group (both P<0.05). The interaction of GBE×CUMS of frequency and quantification of sIPSC in the four groups were significant ( F=7.78, 8.96, both P<0.01). The sIPSC frequency and quantification of the CUMS+ Veh group were higher than those of CTRL+ Veh group (both P<0.01), and the above indexes of CUMS+ GBE group were lower than those of CUMS+ Veh group (both P<0.01). As for the sEPSC/sIPSC ratio, GBE×CUMS interaction was significant ( F=5.45, P=0.02). The sEPSC/sIPSC ratio of CUMS+ Veh group (0.09±0.01) was lower than that of CTRL+ Veh group (0.28±0.04) ( P<0.01), and the sEPSC/sIPSC ratio of CUMS+ GBE group (0.14±0.03) was higher than that of CUMS+ Veh group ( P<0.05). Conclusion:Ginkgo biloba extract can improve the depression-like behavior of mice induced by CUMS, reduce the oxidative stress of mPFC and improve the excitation/inhibition balance of pyramidal neurons in depressive model mice.
RESUMEN
Rho-associated kinases (ROCKs) are serine-threonine protein kinases that act downstream of small Rho GTPases to regulate the dynamics of the actin cytoskeleton. Two ROCK isoforms (ROCK1 and ROCK2) are expressed in the mammalian central nervous system. Although ROCK activity has been implicated in synapse formation, whether the distinct ROCK isoforms have different roles in synapse formation and function in vivo is not clear. Here, we used a genetic approach to address this long-standing question. Both Rock1 and Rock2 mice had impaired glutamatergic transmission, reduced spine density, and fewer excitatory synapses in hippocampal CA1 pyramidal neurons. In addition, both Rock1 and Rock2 mice showed deficits in long-term potentiation at hippocampal CA1 synapses and were impaired in spatial learning and memory based on the water maze and contextual fear conditioning tests. However, the spine morphology of CA1 pyramidal neurons was altered only in Rock2 but not Rock1 mice. In this study we compared the roles of ROCK1 and ROCK2 in synapse formation and function in vivo for the first time. Our results provide a better understanding of the functions of distinct ROCK isoforms in synapse formation and function.
RESUMEN
Objective To explore the correlation of metabolic syndrome (MS ) with low triiodothyronine(T3)syndrome(LT3S ,or It is known as ESS :euthyroid sick syndrome) ,subclinical hypothyroidism (SCH )and a high serum total homocysteine (tHcy )level (hyperhomocysteinemia )in elderly patients. Methods We retrospectively analyzed thyroid function ,serum glucose ,lipids and homocysteine(Hcy)level in 83 MS patients(MS group) ,30 patients with low T3 syndrome(low T3 group) ,41 patients with SCH (SCH group)and 80 healthy individuals (control group)aged over 60 years from January 2015 to March 2017 in outpatient and inpatient departments of our hospital. The correlations of thyroid function and serum Hcy level with MS components were analyzed by multiple Logistic regression model. Results The incidence of low T3 syndrome and SCH in MS patients was 37.3％ (31/83)and 49.4％ (41/83) ,respectively.Low T3 group versus control group showed the lower levels in free triiodothyronine ,FT4 ,folic acid ,and Hcy ,with statistically significant differences (all P<0.05).SCH group versus control group showed a lower levels of FT 4 ,of Hcy and of folic acid ,but an increased TSH level ,with statistically significant differences (all P<0.05).Patients with TSH >5.5 mU/L had decreased FT3 which occurred later than the rise of TSH (P<0.05) .Univariate correlation analysis showed that FT3 was negatively correlated with Hcy (P< 0.01) ,and TSH was negatively correlated with high-density lipoprotein cholesterol(P<0.01).Multivariate linear regression analysis found linear correlations of TSH with triglyceride ,high-density lipoprotein cholesterol ,and Hcy(all P < 0.05).Logistic regression analysis showed that FT3 ,Hcy and TSH are highly associated with hypertension after adjustment for gender and body mass index (all P< 0.05).Decreased FT3(P<0.01) ,elevated Hcy(P<0.05) ,and increased TSH(P<0.05)were independent risk factors for MS in elderly patients. Conclusions The incidences of low T3 syndrome and SCH are increased with aging. FT3 ,TSH ,and Hcy are independent risk factors for MS in the elderly.