Astroglial IFITM3 mediates neuronal impairments following neonatal immune challenge in mice

Interferon‐induced transmembrane protein 3 (IFITM3) ?plays a crucial role in the antiviral responses of Type I interferons (IFNs). The role of IFITM3 in the central nervous system (CNS) is, however, largely unknown, despite the fact that its expression is increased in the brains of patients with neurologic and neuropsychiatric diseases. Here, we show the role of IFITM3 in long‐lasting neuronal impairments in mice following polyriboinosinic‐polyribocytidylic acid (polyI:C, a synthetic double‐stranded RNA)‐induced immune challenge during the early stages of development. We found that the induction of IFITM3 expression in the brain of mice treated with polyI:C was observed only in astrocytes. Cultured astrocytes were activated by polyI:C treatment, leading to an increase in the mRNA levels of inflammatory cytokines as well as Ifitm3. When cultured neurons were treated with the conditioned medium of polyI:C‐treated astrocytes (polyI:C‐ACM), neurite development was impaired. These polyI:C‐ACM‐induced neurodevelopmental abnormalities were alleviated by ifitm3^?/? astrocyte‐conditioned medium. Furthermore, decreases of MAP2 expression, spine density, and dendrite complexity in the frontal cortex as well as memory impairment were evident in polyI:C‐treated wild‐type mice, but such neuronal impairments were not observed in ifitm3^?/? mice. We also found that IFITM3 proteins were localized to the early endosomes of astrocytes following polyI:C treatment and reduced endocytic activity. These findings suggest that the induction of IFITM3 expression in astrocytes by the activation of the innate immune system during the early stages of development has non‐cell autonomous effects that affect subsequent neurodevelopment, leading to neuropathological impairments and brain dysfunction, by impairing endocytosis in astrocytes. GLIA 2013     

Interventions to reduce antipsychotic polypharmacy: A systematic review

BackgroundIt still remains unclear as to how to counteract antipsychotic polypharmacy that remains controversial but common. The objective of this study was to synthesize the clinical evidence to reduce antipsychotic polypharmacy (i.e. use of multiple antipsychotics) in schizophrenia.MethodsA literature search was performed to identify clinical trials that attempted to reduce antipsychotic polypharmacy in patients with schizophrenia by any form of systematic intervention using PubMed as well as MEDLINE, EMBASE, and PsycINFO (last search: June 2012). The search terms included “antipsychotics” and “polypharmacy”. Cross-referencing was also performed.ResultsThe literature search identified 17 studies. Only 3 studies (1 randomized controlled trial and 2 open-label trials) were found that systematically switched antipsychotic polypharmacy to monotherapy. In two of them, more than two thirds of the subjects successfully completed the switch (40/58, 69.0%; 34/44, and 77.3%, respectively) while less than half the subjects tolerated it in the other study (6/14 and 42.9%) although the sample size was very small. On the other hand, 14 studies that examined impacts of interventions have physicians refrain from antipsychotic polypharmacy. While a modest intervention with educational approach alone was effective in three of the five articles, a more assertive intervention that directly cautioned physicians on the use of polypharmacy was effective in 10 of 12 articles.ConclusionThe literature search revealed the paucity of the data. Careful switching from polypharmacy to monotherapy seems feasible in a majority of patients with schizophrenia. Assertive interventions, rather than passive educational approaches alone, appear more effective in reducing antipsychotic polypharmacy.     

Searching for diagnostic properties of novel fluorine-18-labeled d-allose

Annals of Nuclear Medicine - Two fluorine-18-labeled analogues, 3-deoxy-3-[18F]fluoro-d-allose (3-[18F]FDA) and 6-deoxy-6-[18F]fluoro-d-allose (6-[18F]FDA), were synthesized and their potentials of...