ABSTRACT
OBJECTIVE To investigate the protective effect of selective 18 ku translocator protein (TSPO) ligand YL-IPA08 on corticosterone(CORT)-induced apoptosis of BV-2 cells and its potential mecha?nisms. METHODS BV-2 Cells were pretreated with selective TSPO ligand YL-IPA08 1-100 nmol · L-1 and(or) TSPO antagonist PK11195 100 nmol · L-1 for 2 h,and then co-incubated with CORT for another 24 h. The apoptosis rate was measured by flow cytometry. CCK-8 kit was used to test BV-2 cell viability. The protein expression of TSPO was determined by Western blotting. The level of allopreg?nanolone was detected by ELISA kit. RESULTS In line with positive drug-AC-5216, the cell apoptosis rate decreased in YL-IPA08 1-100 nmol · L-1 and CORT co-treatment groups(P<0.01), which was antago?nized by PK11195 100 nmol · L-1 treatment(P<0.05). Cell viability increased in YL-IPA08 100 nmol · L-1and CORT co-treatment groups (P<0.01), which was blocked by PK11195 100 nmol·L-1 treatment(P<0.01). The expression of TSPO and the level of allopregnanolone(P<0.01) were enhanced by YL-IPA08 100 nmol · L-1 pretreatment followed by CORT treatment. The enhancement of allopregnanolone level was blocked by PK11195 100 nmol·L-1 treatment(P<0.05). CONCLUSION YL-IPA08 can protect BV-2 cells from CORT induced apoptosis. The protective effect of YL-IPA08 may be conferred by the increasing level of TSPO expression and allopregnanolone.
ABSTRACT
OBJECTIVE To investigate the effect of overexpession of 18 ku translocator protein (TSPO) on the hippocampal dentate gyrus. METHODS Lentiviral (LV) vectors containing TSPO or the lentiviral sequence were infused into the hippocampus bilateral dentate gyri (2 × 108 TU · mL-1,1 μL per side)of mice. Behavioral tests were carried out. The anxiolytic-like behavior of mice was examined by such means as the elevated plus maze test , the staircase test , light dark box test for 12, 14 and 16 d, two behavioral despair models, tail suspension test and the forced swimming test for 16 and 18 d,respec?tively. Western blotting and ELISA were used to evaluate the TSPO expression and the concentration of allopregnanolone in hippocampal tissue (3 mm in diameter around the injection site on both sides) at the end of tests. RESULTS The results of behavioral experiments showed that TSPO overexpression group deneloped anxiolytic and antidepression-like behavior. LV-TSPO significantly increased the retention time in the central area〔14 ± 4 vs (25 ± 12)s,P<0.05〕. LV-TSPO significantly increased the percentage of entry into open arms entries percentage and the percentage of time spent in open arms time without changing total entries and total time in the elevated plus-maze test〔(13±8)%vs (26±18)%, P<0.05;(6 ± 6)%vs (27 ± 6)%, P<0.05)〕. LV-TSPO significantly decreased the number of rearings without changing the number of steps in staircase test (21±7 vs 12±5,P<0.05). LV-TSPO increased entries into the light area and retention time in light-dark transition test〔(18 ± 8)% vs (26 ± 7)%, P<0.05;72 ± 36 vs (191 ± 90)s, P<0.05)〕but significantly decreased immobility time in the tail suspension test and forced swimming test〔94±33 vs (36±20)s, P<0.01;137±36 vs (90±37)s, P<0.05)〕, without excitatory or inhibitory actions on the central nervous system. At the same time, the level of TSPO expression in hippocampal tissues (3 mm in diameter around the injection site on both sides) was significantly increased, so did the concentration of allopregnanolone (P<0.05). CONCLUSION Overexpression of TSPO in the hippocamus dentate gyrus of mice can induce anxiolytic and antidepressant-like behavior, and the downstream allo?pregnanolone biosynthesis at least partially mediates the behavioral effects.
ABSTRACT
OBJECTIVE To investigate the relationship between the anti-post-traumatic stress disorder(PTSD)effect of sertraline and nitric oxide in fear conditioning rats. METHODS Conditioned fear stress was established by electric shock with a cue tone,and fear extinction training was carried out by giving the rats only tone signals the next day. The rats were treated with sertraline(15 mg · kg-1) intragastrically within 1 h before the experiment for 8 d. Freezing time was tested at the 1st,4th and 7th day after the extinction training in rats. The NO contents were detected by Griess method and the nNOS and iNOS level on amygdala was detected by Western blotting. RESULTS The behavior tests showed that compared with normal control group ,the freezing time was significantly increased in extinction control group and extinction training group(P<0.01),indicating that the conditioned fear model of rats was successfully established. At the 1st and 4th day after conditioned fear extinction training in the rats,freezing time in sertraline(15 mg·kg-1)group was decreased compared with extinction training group (P<0.05). At the 7th day,the freezing time was significantly decreased(P<0.01),indicating that ser?traline reversed the fear response. At the same time,the contents of NO,nNOS and iNOS on amygdala of rats in sertraline group were lower than that in extinction training group(P<0.01). CONCLUSION Sertraline can promote extinction of conditioned fear memory,suggesting that sertraline has anti-PTSD effects on the model of fear condition in rats. The underlying mechanisms may be connected with NO.
ABSTRACT
γ-aminobutyric acid A(GABAA)receptor is one of the ligand-gated ion channel receptors expressing widely in the brain. As the major inhibitory neurotransmitter receptor, GABAA receptor is involved in the regulation of many physiological mechanisms. Imbalance expression of the receptor may lead to neuropsychiatric disorders such as schizophrenia,depression, epilepsy,post-traumatic stress disorder (PTSD) syndrome,neurofibromatosis type 1 and fragile X syndrome. Clinically classic benzodiazepines acting on GABAA receptor can be used for the auxiliary treatment of various neuropsychiatric disorders,which supports the potential therapeutic value of GABAA receptor for these diseases. The paper describes the molecular structure and subtypes of GABAA receptor and further reviews the progress in the link between GABAA receptor and neuropsychiatric disorders in order to provide a new target for the drug therapy development of neuropsychiatric disorders.
ABSTRACT
Objective To study how to improve velopharyngeal ring ligafion procedure by using ring ligator in velopharyngeal ring ligatian procedure and settle the problem that there is no standard to measure the interspace of the cavity of pharynx.Methods Select some deft palate patients who were between 3 to 17 ages.Then made five groups according to age (3 to 5,6 to 8,9 to 11,12 to 14,15 to 17).Then made five different types of ring ligators accrding to the normal size of the cavity of pharynx of different ages.Results The ring ligators were easily used and all the patients were repaired satisfied.Conclusion The application of ring ligator in velopharyngeal ring ligation procedure is simple and feasible.