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1.
Neuropharmacology ; 125: 117-128, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28655607

ABSTRACT

The 18 kDa translocator protein (TSPO) is a five transmembrane domain protein that plays a crucial role in neurosteroid (e.g., allopregnanolone) synthesis by promoting the transport of cholesterol to the inner mitochondrial membrane. This protein is predominantly expressed in steroid-synthesizing tissues, including the central and peripheral nervous system, affecting stress-related disorders such as anxiety and depression. Recent studies have focused on the hippocampal dentate gyrus, which is very important for involvement of anxiety and depression. However, the exact role that TSPO plays in the pathophysiology of anxiety and depression and the involvement of the hippocampal dentate gyrus in regulating these behavioural effects remain elusive. This study used the lentiviral vectors mediating TPSO overexpression to assess the effects of TPSO overexpression in the hippocampal dentate gyrus on anxiolytic and antidepressant-like behavioural effects in mice. The expression of TSPO and the concentration of allopregnanolone in hippocampus tissues (3 mm in diameter around the injection site on both sides) were measured by Western blot and ELISA, respectively. The results indicated that microinjection of the LV-TSPO resulted in a significant increase in TSPO expression and allopregnanolone concentration in the hippocampus. Moreover, TSPO overexpression of the mouse hippocampal dentate gyrus generated significant anxiolytic and antidepressant-like behavioural effects in a series of behavioural models. These effects were completely blocked by the TSPO antagonist PK11195 (3 mg/kg, intraperitoneally) and the 5α-reductase inhibitor finasteride (5 mg/kg,intraperitoneally). Meanwhile, the increased allopregnanolone was also reversed by PK11195 and finasteride. In addition, neither PK11195 nor finasteride had an effect on the expression of TSPO. Overall, our results are the first to suggest that the overexpression of TSPO in the hippocampal dentate gyrus produced anxiolytic and antidepressant-like behavioural effects that are partially mediated by downstream allopregnanolone biosynthesis. Our results suggest that TSPO would be a potential anxiolytic and antidepressant therapeutic target.


Subject(s)
Anxiety/metabolism , Dentate Gyrus/metabolism , Depression/metabolism , Receptors, GABA/metabolism , 5-alpha Reductase Inhibitors/pharmacology , Animals , Dentate Gyrus/drug effects , Finasteride/pharmacology , Genetic Vectors/administration & dosage , Isoquinolines/pharmacology , Lentivirus/genetics , Male , Mice, Inbred ICR , Motor Activity/drug effects , Motor Activity/physiology , Pregnanolone/metabolism , Psychotropic Drugs/pharmacology , Receptors, GABA/genetics
2.
J Ethnopharmacol ; 179: 9-15, 2016 Feb 17.
Article in English | MEDLINE | ID: mdl-26719283

ABSTRACT

ETHNOPHARMACOLOGY RELEVANCE: Albiflorin, a monoterpene glycoside, is a main component of Radix paeoniae Alba, which could be a Chinese herbal medicine used in the treatment of psychiatric disorders. However, the exact role of albiflorin in depression is poorly understood. AIM OF THE STUDY: The current study aimed to evaluate the antidepressant effect of albiflorin in mice and rats, and the possible mechanism was also determined. MATERIALS AND METHODS: The antidepressant-like effects of albiflorin was determined by using animal models of depression including forced swim and tail suspension tests in mice and chronic unpredictable stress (CUS) in rats. The acting mechanism was explored by determining the effect of albiflorin on the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus by western blot and the levels of monoamine in the hippocampus by HPLC. RESULTS: Our results showed that 7 days treatment with albiflorin significantly decreased immobility time in the forced swimming test (FST) and the tail suspension test (TST) at doses of 3.5, 7.0 and 14.0mg/kg without alter the locomotor activity in mice. Moreover, western blot analysis showed that albiflorin could increase the expression of BDNF in the hippocampus. We further exposed rats to a chronic unpredictable stress (CUS) protocol for a period of 35d to induce depressive-like behaviors. We found that chronic treatment with albiflorin, at doses of 7.0 and 14.0mg (i.g., once daily for 35d), restored the sucrose preference in CUS rats. In the open-field test, albiflorin significantly increased the number of crossings and rearings in the CUS rats at three doses. Moreover, chronic treatment with albiflorin up-regulated the hippocampal BDNF expression levels and the hippocampal 5-HT, 5-HIAA, and NA levels. CONCLUSION: Albiflorin produced significant antidepressant-like effects, which were closely related to the hippocampal 5-HT/NE increase and BDNF expression. Our data indicated that albiflorin could be a potential anti-depressant drug.


Subject(s)
Antidepressive Agents/therapeutic use , Bridged-Ring Compounds/therapeutic use , Paeonia/chemistry , Plant Extracts/therapeutic use , Animals , Antidepressive Agents/chemistry , Biogenic Monoamines/metabolism , Brain-Derived Neurotrophic Factor/biosynthesis , Bridged-Ring Compounds/chemistry , Food Preferences , Hindlimb Suspension/psychology , Hippocampus/drug effects , Hippocampus/metabolism , Male , Mice , Mice, Inbred ICR , Motor Activity/drug effects , Plant Extracts/chemistry , Rats , Rats, Wistar , Stress, Psychological/psychology , Swimming/psychology
3.
Shanghai Kou Qiang Yi Xue ; 17(4): 380-2, 2008 Aug.
Article in Chinese | MEDLINE | ID: mdl-18784877

ABSTRACT

PURPOSE: To evaluate the recovery of infraorbital nerve injury after middle facial fracture. METHODS: 28 patients with infraorbital nerve injury were examined in l month, 3 months, 6 months and 12 months after operation by using sharp-blunt test, two-point discrimination,electric pain response test. The data were analyzed with SPSS12.0 software package for Student's t test. RESULTS: 25 cases (25 of 28) with injured nerve recovered normally.The average time of recovery was 25 weeks. The injured nerve didnot recover in 3 of 28. No chronic neuropathic pain was found. CONCLUSIONS: Most nerve dysfunctions following middle facial fracture are reversible and temporary,very few are permanent. If the injured nerve doesn't recover within 6 months, infraorbital nerve decompression may be selected to promote the recovery of the nerve function.


Subject(s)
Facial Bones/injuries , Facial Nerve Injuries/therapy , Fractures, Bone/complications , Fractures, Bone/therapy , Decompression, Surgical , Humans
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