Increased Levels of C1q in the Prefrontal Cortex of Adult Offspring after Maternal Immune Activation: Prevention by 7,8-Dihydroxyflavone

OBJECTIVE: Prenatal infection is implicated in the etiology of schizophrenia. The objective of this paper is to study the role of complement protein C1q in the psychosis of adult offspring after maternal immune activation (MIA). In addition, effect of 7,8-dihydroxyflavone (7,8-DHF: a tropomyosin receptor kinase B [TrkB] agonist) was also examined. METHODS: Western blot analysis of C1q in the brain regions from adult offspring after prenatal poly(I:C) (5.0 mg/kg/day from E12 to E17) exposure was performed. 7,8-DHF or vehicle was given from 4 to 8-weeks old. RESULTS: Expression of C1q in the prefrontal cortex (PFC) of adult offspring from poly(I:C)-treated pregnant mice was significantly higher than that of control group. Early treatment with 7,8-DHF during juvenile and adolescent stages could prevent an increase of C1q in the PFC of adult offspring after MIA. CONCLUSION: Therefore, it is likely that increased C1q expression in the frontal cortex may play a role in the behavioral abnormalities of adult offspring after MIA. Furthermore, supplementation with a TrkB agonist such as 7,8-DHF during the prodromal stage may have prophylactic effects on the behavioral abnormalities after MIA.

Antidepressant Effects of Ketamine on Depression-like Behavior in Juvenile Mice after Neonatal Dexamethasone Exposure

OBJECTIVE: Pediatric depression is associated with significant functional impairment at school and at work. Recently, we reported on depression-like behavior in juvenile mice neonatally exposed to dexamethasone (DEX) as a potential animal model for pediatric depression. The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has promoted rapid and long-lasting antidepressant effects in patients with treatment-resistant major depression. This study was conducted to examine whether ketamine had antidepressant effects in juvenile mice after neonatal DEX exposure. METHODS: A single dose (10 mg/kg) of ketamine or vehicle was injected into juvenile mice at days 29-32 after neonatal DEX (or saline) exposure (days 1-3). The sucrose preference test, tail suspension test, and forced swimming test were performed 24, 40, and 46 hours, respectively, after injection of ketamine. RESULTS: Ketamine (10 mg/kg) significantly improved depression-like behavior in DEX-treated juvenile mice. CONCLUSION: This finding suggests that ketamine confers antidepressant effects in an animal model of pediatric depression.

Erratum: Figure Correction

The Figure 1A was given incorrectly.

Effects of Brilliant Blue G on Serum Tumor Necrosis Factor-alpha Levels and Depression-like Behavior in Mice after Lipopolysaccharide Administration

OBJECTIVE: Accumulating evidence suggests that inflammation plays a role in the pathophysiology of major depression. The adenosine triphosphate (ATP)-sensitive P2X7 receptor (P2X7R) plays a crucial role in microglial activation caused by inflammation. The dye brilliant blue G (BBG) is a P2X7R antagonist. This study examined whether BBG shows antidepressant effects in an inflammation-induced model of depression. METHODS: We examined the effects of BBG (12.5, 25, or 50 mg/kg) on serum tumor necrosis factor-alpha (TNF-alpha) levels after administering the bacterial endotoxin lipopolysaccharide (LPS; 0.5 mg/kg) and the effects of BBG (50 mg/kg) on depression-like behavior in the tail-suspension test (TST) and forced swimming test (FST). RESULTS: Pretreatment with BBG (12.5, 25, or 50 mg/kg) significantly blocked the increase in serum TNF-alpha levels after a single dose of LPS (0.5 mg/kg). Furthermore, BBG (50 mg/kg) significantly attenuated the increase in immobility time in the TST and FST after LPS (0.5 mg/kg) administration. CONCLUSION: The results suggest that BBG has anti-inflammatory and antidepressant effects in mice after LPS administration. Therefore, P2X7R antagonists are potential therapeutic drugs for inflammation-related major depression.

Reconstruction of forefoot skin defect with island flap pedicled with lateral tarsal artery / 中华整形外科杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic effect of island flap pedicled with lateral tarsal artery for forefoot skin defect.</p><p><b>METHODS</b>From March 2007 to January 2009, 12 cases with forefoot skin defects were treated by reversed island flap pedicled with lateral tarsal artery.</p><p><b>RESULTS</b>All the flaps survived completely with a followed-up period of 8-22 months, 13 months in average. The flaps and skin grafts had soft texture and a similar color as the surrounding skin. The flaps had a suitable thickness with deep pain sensation. Shallow touch and pain sensation recovered in the skin graft and within 1-2 cm of the flap edge, which was graded as S1-S2. There was no problem in shoes-wearing and walking. No flap ulcer happened.</p><p><b>CONCLUSION</b>Island flap pedicled with lateral tarsal artery is suitable for forefoot skin defect, leaving less morbidity to donor site.</p>

In Vivo Evaluation of 11C-labeled Three Radioligands for Glycine Transporter 1 in the Mouse Brain

OBJECTIVE: Glycine transporter 1 (GlyT-1) is one of the most attractive therapeutic targets for schizophrenia. There is great interest in developing radioligands for in vivo imaging of GlyT-1 in the brain using positron emission tomography. Here, we report the properties of three novel non-sarcosine-based radioligands [11C]CHIBA-3007, [11C]CHIBA-3009, and [11C]CHIBA-3011, for GlyT-1 imaging in the mouse brain in vivo. METHODS: The three radioligands were synthesized by N-[11C] methylation of the corresponding desmethyl precursor. A pharmacological characterization of these radioligands for in vivo imaging of GlyT-1 in the brain was conducted using male ddY mice. RESULTS: [11C]CHIBA-3009 and [11C]CHIBA-3011 were scarcely incorporated into the brain, whereas [11C]CHIBA-3007 showed slight but considerable brain uptake. Regional brain uptake of [11C]CHIBA-3007 (medulla oblongata>cerebellum>cortex) was similar to the distribution of the GlyT-1 protein. However, pretreatment with CHIBA-3007 (1 mg/kg) or the GlyT-1 selective inhibitor ALX5407 (N-[(3R)-3-([1,1'-Biphenyl]-4-yloxy)-3-(4-fluorophenyl)propyl]-N-methylglycine) (30 mg/kg) did not significantly decrease brain uptake of [11C]CHIBA-3007, suggesting low specific binding to GlyT-1. Pretreatment with cyclosporin A significantly increased brain uptake of [11C]CHIBA-3009 and [11C]CHIBA-3011, suggesting a role for P-glycoprotein in the brain uptake of these ligands. All three radioligands were rapidly degraded intact forms were 3-18% in plasma and 15-74% in the brain at 15 min after injection. CONCLUSION: The results suggest that these three radioligands are not suitable for in vivo imaging of GlyT-1 in the brain because of low brain uptake and rapid metabolism. Further structural refinement is necessary to enhance brain uptake.