Reexamination of N-terminal domains of syntaxin-1 in vesicle fusion from central murine synapses.

Syntaxin-1 (STX1) and Munc18-1 are two requisite components of synaptic vesicular release machinery, so much so synaptic transmission cannot proceed in their absence. They form a tight complex through two major binding modes: through STX1's N-peptide and through STX1's closed conformation driven by its Habc- domain. However, physiological roles of these two reportedly different binding modes in synapses are still controversial. Here we characterized the roles of STX1's N-peptide, Habc-domain, and open conformation with and without N-peptide deletion using our STX1-null mouse model system and exogenous reintroduction of STX1A mutants. We show, on the contrary to the general view, that the Habc-domain is absolutely required and N-peptide is dispensable for synaptic transmission. However, STX1A's N-peptide plays a regulatory role, particularly in the Ca2+-sensitivity and the short-term plasticity of vesicular release, whereas STX1's open conformation governs the vesicle fusogenicity. Strikingly, we also show neurotransmitter release still proceeds when the two interaction modes between STX1A and Munc18-1 are presumably intervened, necessitating a refinement of the conceptualization of STX1A-Munc18-1 interaction.

Antidepressant-like effect of Albizia zygia root extract in murine models.

Background Albizia zygia (DC.) J.F. Macbr. (Leguminosae) has been used to treat mental disorders in traditional African medicine. Nonetheless, there is limited scientific evidence to justify its present use. The aim of this study was to evaluate the antidepressant activity of the hydroethanolic extract of A. zygia roots (AZE) in murine models. Methods AZE was evaluated in the tail suspension test, forced swim test, and the repeated open-space swim test of depression. In order to elucidate the mechanisms of action, the activity of AZE was re-evaluated after treating mice with selective inhibitors of monoamine biosynthesis. The potential of AZE to influence spontaneous locomotion was also examined. Results AZE (100-1000 mg/kg, p.o.) reduced the immobility time of mice in the tail suspension and forced swim tests (at least p < 0.05). In the repeated open-space swim test, AZE reduced the immobility time (at least p < 0.05) while concomitantly increasing the distance swam by mice (p < 0.01). However, the antidepressant-like activity of AZE was attenuated by α-methyl-para-tyrosine and reserpine (p < 0.0001) but not para-chlorophenylalanine. Conclusions The results of this study indicate that AZE possesses antidepressant-like properties and support the traditional use of AZE for the treatment of depression.

Albizia zygia root extract exhibits antipsychotic-like properties in murine models of schizophrenia.

BACKGROUND: The root extract of Albizia zygia (DC.) J.F. Macbr. (Leguminosae) is used to manage mental disorders in African traditional medicine. However, its value, particularly, against negative and cognitive symptoms of schizophrenia have not been evaluated. AIM: The aim of this study was to evaluate the antipsychotic properties of the hydroethanolic root extract of Albizia zygia (AZE) against positive, negative and cognitive symptoms of schizophrenia in animal models. MATERIALS AND METHODS: The effects of AZE (30-300 mg kg-1) were evaluated against apomorphine-induced cage climbing as well as ketamine -induced hyperlocomotion, -enhanced immobility, -impaired social interaction and novel object recognition. The propensity of AZE to induce catalepsy and to attenuate haloperidol-induced catalepsy were also investigated. RESULTS: AZE 30-300 mg kg-1 significantly reduced apomorphine-induced climbing behaviour as well as ketamine-induced hyperlocomotion, immobility and object recognition deficits (at least P < 0.05). Moreover, the extract showed no cataleptic effect but significantly inhibited haloperidol-induced catalepsy at a dose of 30 mg kg-1 (P < 0.05). CONCLUSION: The root extract of Albizia zygia exhibited an antipsychotic-like activity in mice with potential to alleviate positive, negative and cognitive symptoms of schizophrenia.