Neuroprotective effect and mechanism of Zuogui Jiangtang Jieyu Formula on diabetes mellitus complicated with depression model rats based on CX3CL1-CX3CR1 axis / 中国中药杂志

Based on the CX3C chemokine ligand 1(CX3CL1)-CX3C chemokine receptor 1(CX3CR1) axis, this study explored the potential mechanism by which Zuogui Jiangtang Jieyu Formula(ZGJTJY) improved neuroinflammation and enhanced neuroprotective effect in a rat model of diabetes mellitus complicated with depression(DD). The DD rat model was established by feeding a high-fat diet combined with streptozotocin(STZ) intraperitoneal injection for four weeks and chronic unpredictable mild stress(CUMS) combined with isolated cage rearing for five weeks. The rats were divided into a control group, a model group, a positive control group, an inhibitor group, and a ZGJTJY group. The open field test and forced swimming test were used to assess the depression-like behaviors of the rats. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the expression levels of the pro-inflammatory cytokines interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in plasma. Immunofluorescence staining was used to detect the expression of ionized calcium-binding adapter molecule 1(Iba1), postsynaptic density protein-95(PSD95), and synapsin-1(SYN1) in the hippocampus. Hematoxylin-eosin(HE) staining, Nissl staining, and TdT-mediated dUTP nick end labeling(TUNEL) fluorescence staining were performed to assess hippocampal neuronal damage. Western blot was used to measure the expression levels of CX3CL1, CX3CR1, A2A adenosine receptor(A2AR), glutamate receptor 2A(NR2A), glutamate receptor 2B(NR2B), and brain-derived neurotrophic factor(BDNF) in the hippocampus. Compared with the model group, the ZGJTJY group showed improved depression-like behaviors in DD rats, enhanced neuroprotective effect, increased expression of PSD95, SYN1, and BDNF(P<0.01), and decreased expression of Iba1, IL-1β, and TNF-α(P<0.01), as well as the expression of CX3CL1, CX3CR1, A2AR, NR2A, and NR2B(P<0.01). These results suggest that ZGJTJY may exert its neuroprotective effect by inhibiting the CX3CL1-CX3CR1 axis and activation of hippocampal microglia, thereby improving neuroinflammation and abnormal activation of N-methyl-D-aspartate receptor(NMDAR) subunits, and ultimately enhancing the expression of synaptic-related proteins PSD95, SYN1, and BDNF in the hippocampus.

Effects of Aerobic Exercises on the Expression of SYP and PSD-95 in Prefrontal Lobe of Rats with Brain Aging Induced by D-galactose / 中国运动医学杂志

Objective To observe the effect of aerobic exercises on the expression of synaptophysin (SYP)and postsynaptic density protein-95 (PSD-95) in the prefrontal lobe of brain-aging rats induced by D-galactose (D-gal) and to explore the underlying mechanism of aerobic exercises relieving learning and memory deficits in the brain-aging process.Methods Thirty-six 3-month-old male Sprage-Dawley rats were randomly divided into a saline control group (C),a D-gal control group (D),and a D-gal and aerobic exercises group (DE),each of 12.The rats in both group D and DE were injected D-gal (100 mg/kg body weight) abdominally every day for 6 consecutive weeks,while those in group C were injected the same amount of saline.Meanwhile,the rats in group DE had performed aerobic swimming for 1 hour daily,while the other two groups did not do any exercises.Then,the Morris Water Maze (MWM) test was performed to estimate the learning and memory abilities.The immunofluorescence technology,Western blotting and real-time PCR were used to determine the expression levels of SYP,PSD-95,SYP mRNA and PSD-95 mRNA in the prefrontal lobe.Results In the process of navigation training,all animals' escape latencies shortened gradually,indicating that each rat was able to learn to locate the submerged platform.The rats in group C and DE showed best performance on day 3 and no significant improvement was observed thereafter,whereas those in group D improved at a slower pace,and reached maximal performance on day 5.On the 2nd,3rd and 4th days of the navigation training,the average escape latency of group D was significantly longer than that of group C and group DE (P＜0.05),while on the 1st,5th and 6th days,there was no significant difference among the 3 groups.In the probe trial,rats in group D spent significantly less time in the target quadrant compared with both group C and DE (P＜0.05),and rats in group C and DE crossed where the platform was fixed significanlty more often than group D (P＜0.05).The expression levels of SYP and SYP mRNA in the prefrontal lobe of rats in group D were significantly lower than group C (P＜0.01),and group DE (P＜ 0.05).Compared with group C,the expression levels of PSD-95 and PSD mRNA in the prefrontal lobe of rats in group D declined significantly (P＜0.01).There was no significant difference in PSD-95 expression between group D and DE,but the level of PSD-95 protein molecule of group DE was significantly higher than that of group D (P＜0.05).Conclusions The aerobic exercises can ameliorate the deficits of SYP and PSD-95 expression in the frontal cortex of aging rats induced by D-gal to some extent,and improve their learning and memory abilities.

O ciclo da vesícula sináptica, espinhos dendríticos e a transdução de sinal / Synaptic vesicle cycle, dendritic spines and signal transduction

No sistema nervoso, a sinapse é a estrutura que permite a um neurônio passar um sinal elétrico ou químico a outro neurônio ou outra célula (muscular ou glandular). A palavra sinapse vem de "synaptein", palavra que Sir Charles Scott Sherrington e seus colegas acunharam do grego "syn" (junto) e "haptein"(afivelar). As sinapses podem ser separadas entre elétricas e químicas, porém a maior parte da transmissão sináptica é realizada através das sinapses químicas. Apesar das sinapses químicas terem uma resposta mais lenta que as elétricas, elas possuem a vantagem da amplificação do sinal gerada através de uma cascata de segundos mensageiros. As sinapses químicas podem ser excitatórias ou inibitórias e são caracterizadas por um terminal pré-sináptico (onde estão presentes as vesículas que contêm os neurotransmissores) em contato com um terminal pós-sináptico (onde estão presentes os receptores ionotrópicos e metabotrópicos para esses neurotransmissores) separados pela fenda sináptica. As sinapses típicas acontecem sobre axônios (axo-axônicas), sobre dendritos (axo-dendríticas), sobre o soma de outro neurônio (axo-somáticas) e sobre os espinhos dendríticos...

In the nervous system, the synapse is the structure that allows a neuron pass an electrical or chemical signal to another neuron or another cell (muscle or glandular). The word synapse comes from "synaptein" that Sir Charles Scott Sherrington and his colleagues minted from the Greek "syn" (together) and "haptein"(buckling). Most part of the synaptic transmission is performed through chemical synapses. Chemical synapses have a slower response than the electric ones; they have the advantage of amplifying the signal generated through a cascade of second messengers. Chemical synapses can be excitatory or inhibitory and are characterized by a presynaptic terminal (where there are vesicles that contain the neurotransmitters) in contact with a postsynaptic terminal (where there are the ionotropic and metabotropic receptors) separated by the synaptic cleft. Synapses can occur on axons (axo-axonal), on dendrites (axodendritic), on soma (axo-somatic) and on dendritic spines...