Functional coupling of Tmem74 and HCN1 channels regulates anxiety-like behavior in BLA neurons.

Anxiety disorders are the most prevalent psychiatric disorders, but their pathogenic mechanism remains poorly understood. Here, we report that transmembrane protein 74 (TMEM74), which contains two putative transmembrane domains and exhibits high levels of mRNA in the brain, is closely associated with the pathogenesis of anxiety disorders. TMEM74 was decreased in the serum of patients with anxiety and the basolateral amygdaloid nucleus (BLA) in chronic stress mice. Furthermore, genetic deletion of Tmem74 or selective knockdown of Tmem74 in BLA pyramidal neurons resulted in anxiety-like behaviors in mice. Whole-cell recordings in BLA pyramidal neurons revealed lower hyperpolarization-activated cation current (Ih) and greater input resistance and excitability in Tmem74-/- neurons than in wild-type neurons. Accordingly, surface expression of hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels was also lower in the BLA of Tmem74-/- mice. The Ih current blocker ZD7288 mimicked these effects in BLA pyramidal neurons in wild-type mice but not in Tmem74-/- mice. Consistent with the improvement in anxiety-like behaviors, Tmem74 overexpression restored HCN1 channel trafficking and pyramidal neuron excitability in the BLA of Tmem74-/- and chronic stress mice. Mechanistically, we demonstrate that interactions between Tmem74 and HCN1 are physiologically relevant and that transmembrane domain 1 (TM1) is essential for the cellular membrane localization of Tmem74 to enhance Ih. Together, our findings suggest that Tmem74 coupling with HCN1 acts as a critical component in the pathophysiology of anxiety and is a potential target for new treatments of anxiety disorders.

[Mechanisms of Phosphorus Removal by Modified Zeolites Substrates Coated with Zn-LDHs in Laboratory-scale Vertical-flow Constructed Wetlands].

Zn-Layered double hydroxides (LDHs) were selected to carry out the experiment in present work based on the previous research results. According to the co-precipitation method, three kinds of different Zn-LDHs (FeZn-LDHs, CoZn-LDHs and AlZn-LDHs) were synthesized by ZnCl2, FeCl3, AlCl3, and CoCl3 solution in alkaline conditions and Zn-LDHs were in-situ coated on the surface of natural zeolites. With the filling of the natural and three kinds of Zn-LDHs modified zeolites in the columns, test experiments were conducted to study the removal performance of phosphorus in vertical-flow constructed wetlands. The results showed that: compared with the natural zeolites, the removal rates of phosphorus by the three kinds of Zn-modified zeolites were greatly improved, especially for FeZn-LDHs. Moreover, the maximum adsorption capacity and the desorbed performance of phosphate were enhanced by the Zn-LDHs coated modification. The adsorption type of phosphate was converted from physical adsorption to chemical adsorption. Through reasonable selection of the type of zeolite and the method of modification, Zn-LDHs modified zeolites could be used to enhance the removal of nitrogen and phosphorus for the eutrophic water.

[Coating modification of anthracite substrates in vertical-flow constructed wetlands by LDHs synthesized from different metal compounds and the nitrogen removal efficiencies].

As one kind of vertical-flow constructed wetlands substrates, anthracite was selected in this experiment. LDHs (layered double hydroxides) were synthesized in alkaline conditions by co-precipitation of different kinds of metal compounds, such as CaCl2, ZnCl2, MgCl2, FeCl3, AlCl3, CoCl3. The synthesized LDHs were in-situ coated onto the surface of anthracite substrate to achieve the aim of modification. Simulated test columns were constructed to study the nitrogen removal efficiency of the urban sewage using the original anthracite substrates and 9 kinds of modified anthracite substrates. The results showed that: LDHs synthesized by all the 9 different kinds of methods could effectively modify the anthracite substrate by in-situ coating. With Mg2+ involved in the synthesis of modified substrates, good TN and ammonia nitrogen removal efficiencies were observed. The modified anthracite substrates coated with MgCo-LDHs had the optimal performance with average TN and ammonia nitrogen removal efficiencies of higher than 80% and 85%, respectively. The ammonia nitrogen removal efficiencies by the modified anthracite substrates coated by LDHs reacted with Mg2+ and Fe3+ were also high. The ammonia nitrogen removal efficiencies by modified anthracite substrates coated with CaFe-LDHs and MgFe-LDHs were higher than 85%.

[Analysis on the removal efficiency and mechanisms of phosphorus by modified zeolites substrates coated with LDHs reacted by different metal compounds in laboratory-scale vertical-flow constructed wetlands].

Six kinds of metal compounds which were CaCl2 , ZnCl2, MgCl2, FeCl3, AlCl3, and CoCl3 were formed nine kinds of different combinations in the alkaline conditions to synthesized LDHs (Layered Double Hydroxides), which were in-situ coated on the surface of zeolites. With the filling of the original and nine kinds of modified zeolites in the columns to simulate a laboratory-scale vertical-flow constructed wetland system, the experiments of purified phosphorus were conducted. Combined removal efficiency with adsorption isotherm data of the ten kinds of zeolites, mechanism for strengthening the removal rates of the phosphorus by the modified zeolites was studied. The results showed that compared with the original zeolites, the removal rates of the phosphorus by nine kinds of modified zeolites were enhanced with various degrees. In the cases of Zn involved in the modified zeolites, the removal efficiencies of phosphorus reached a high quality. Especially, the ZnFe-LDHs had the average removal rates of the total phosphorus, the dissolved phosphorus and the phosphate were over 90%, and its maximum adsorption capacity of the phosphorus was three times higher than that of the original zeolites. Therefore, by means of increasing the adsorption capacity and improving the chemical adsorption ability of phosphorus, the modification to coated LDHs on the zeolites reached the aim of strengthening the purification of the phosphorus.

[Event-related potentials P300 with memory function and psychopathology in first-episode paranoid schizophrenia].

OBJECTIVE: To investigate the variability of event-related potentials P(300) and the relationship with memory function/psychopathology in patients with first-episode paranoid schizophrenia. METHODS: Thirty patients with first-episode paranoid schizophrenia (patient group) and twenty health subjects (control group) were enrolled in the study. The auditory event-related potentials P300 at the scalp electrodes Cz, Pz and Wechsler Memory Scale (WMS) were examined in both groups, Positive And Negative Syndrome Scale (PANSS) was evaluated in patient group. RESULTS: In comparison with control group, patients had longer latency of P300 [(390.6 ± 47.6)ms at Cz and (393.3 ± 50.1)ms at Pz] (P<0.01), lower amplitude of P300 [(7.7 ± 3.4) µV at Cz and (8.5 ± 3.9)µV at Pz] (P<0.05-0.01). The memory quotient (88.1 ± 10.0) scores and short-term memory, immediate memory in patient group were damaged significantly (P<0.05-0.01). In patient group, the latency of P300 was correlated positively with PANSS scores and negatively with WMS scores (P<0.05-0.01). CONCLUSION: First-episode paranoid schizophrenia has memory deficit, which can be evaluated comprehensively by P300 and WMS. The longer latency of P300 might be associated with the increased severity of first-episode paranoid schizophrenia.

[Chronic mild stress stimulates nitric oxide production in rat brain cortex and hippocampus].

OBJECTIVE: To evaluate the nitric oxide (NO) levels in rat brain cortex and hippocampus after chronic mild stress. METHODS: Sixteen male Sprague-Dawley rats were allocated into control group and model group randomly. Model rats were induced by consecutive chronic mild stress; weight gain, open field test and sucrose solution consumption were investigated before and after procedure. Nitric oxide contents in prefrontal cortex and hippocampus were determined by spectrophotometric assays. RESULT: Decreased locomotion, loss of interest and anhedonia were observed in chronic mild stress rat model group. Nitric oxide contents in prefrontal cortex and hippocampus were significantly higher in chronic mild stress group [(31.00 +/-2.55)nmol/mg.pro and (38.11 +/-1.73)nmol/mg.pro, respectively] than those in control group [(26.97 +/-1.38)nmol/mg.pro and (36.06 +/-0.87)nmol/mg.pro, respectively] (P <0.05). CONCLUSION: Chronic stress can stimulate NO release, and dysfunction of nitric oxide pathway may be involved in development of depression.

Imbalanced free radicals and antioxidant defense systems in schizophrenia: a comparative study.

OBJECTIVE: To examine changes of blood oxidative-antiovidative level in schizophrenic patients and its relationship with clinical symptoms. METHODS: Forty-six Chinese patients met DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-IV) criteria for schizophrenia and fifty age- and sex-matched healthy controls were enrolled in the present study. Baseline psychiatric symptom severity was assessed with brief psychiatric rating scale, positive and negative syndrome scale on the blood draw day. Fresh blood samples were collected to measure levels of nitric oxide and lipid peroxide in plasma as well as activities of superoxide dismutase, catalase and glutathione peroxidase in red blood cells by spectrophotometric assays simultaneously. RESULTS: Comparison of the biochemical parameters indicated that the level of nitric oxide and lipid peroxide increased in patient group, which represented a positive correlation with positive scale scores; while the activities of three critical enzymes decreased and showed a negative linear correlation. CONCLUSION: This study showed that there are dysregulation of free radical metabolism and poor activities of the antioxidant defense systems in schizophrenic patients. Excess free radicals formation may play a critical role in the etiology of schizophrenia. Using antioxidants might be an effective therapeutic approach to partially alleviate or prevent the symptoms of schizophrenia.