Interleukin33 deficiency causes tau abnormality and neurodegeneration with Alzheimer-like symptoms in aged mice.

This corrects the article DOI: 10.1038/tp.2017.142.

Interleukin33 deficiency causes tau abnormality and neurodegeneration with Alzheimer-like symptoms in aged mice.

Late-onset Alzheimer's disease (AD) remains a medical mystery. Recent studies have linked it to impaired repair of aged neurons. Potential involvement of interleukin33 (IL33) in AD has been reported. Here we show that IL33, which was expressed by up to 75% astrocytes in the aged brains, was critical for repair of aged neurons. Mice lacking Il33 gene (Il33-/-) developed AD-like disease after 60-80 weeks, which was characterized by tau abnormality and a heavy loss of neurons/neurites in the cerebral cortex and hippocampus accompanied with cognition/memory impairment. We detected an abrupt aging surge in the cortical and hippocampal neurons at middle age (40 weeks). To counter the aging surge, wild-type mice rapidly upregulated repair of DNA double-strand breaks (DSBs) and autophagic clearance of cellular wastes in these neurons. Il33-/- mice failed to do so, but instead went on to develop rapid accumulation of abnormal tau, massive DSBs and abnormal autophagic vacuoles in these neurons. Thus, uncontrolled neuronal aging surge at middle age due to lack of IL33 resulted in neurodegeneration and late-onset AD-like symptome in Il33-/- mice. Our study also suggests that the aging surge is a time to search for biomarkers for early diagnosis of AD before massive neuron loss.

Exposure to Perinatal Infections and Bipolar Disorder: A Systematic Review.

Bipolar disorder (BD) is a debilitating psychiatric disorder and a growing global public health issue. Notwithstanding BD has been conceptualized as a neuroprogressive illness, there are some evidences to suggest a role for neurodevelopmental pathways in the patho-etiology of this disorder. Evidences on the associations between perinatal infections and risk for bipolar disorder have been inconsistent across studies. Here, we performed a systematic review of observational studies on the relationship between exposure to perinatal pathogens and bipolar disorder. A computerized literature search of the PubMed, Embase, and PsyINFO databases till January 31(st), 2015 was performed. Twenty-three studies ultimately met inclusion criteria. Studies investigated exposure to several pathogens namely Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Herpes simplex virus-1 (HSV-1), Herpes simplex virus-2 (HSV-2), Human herpesvirus 6 (HHV-6), Toxoplasma gondii, Influenza, and Varicella zoster virus (VZV). Overall, studies provided mixed evidences. Thus, contrary to schizophrenia, the role of perinatal infections as risk factors for BD remain inconclusive. Larger studies with a prospective design would be necessary to elucidate the role of previous exposure to infectious agents as a potential risk factor for BD.

Nephronophthisis and retinal degeneration in tmem218-/- mice: a novel mouse model for Senior-Løken syndrome?

Mice deficient in TMEM218 (Tmem218(-/-) ) were generated as part of an effort to identify and validate pharmaceutically tractable targets for drug development through large-scale phenotypic screening of knockout mice. Routine diagnostics, expression analysis, histopathology, and electroretinogram analyses completed on Tmem218(-/-) mice identified a previously unknown role for TMEM218 in the development and function of the kidney and eye. The major observed phenotypes in Tmem218(-/-) mice were progressive cystic kidney disease and retinal degeneration. The renal lesions were characterized by diffuse renal cyst development with tubulointerstitial nephropathy and disruption of tubular basement membranes in essentially normal-sized kidneys. The retinal lesions were characterized by slow-onset loss of photoreceptors, which resulted in reduced electroretinogram responses. These renal and retinal lesions are most similar to those associated with nephronophthisis (NPHP) and retinitis pigmentosa in humans. At least 10% of NPHP cases present with extrarenal conditions, which most often include retinal degeneration. Senior-Løken syndrome is characterized by the concurrent development of autosomal recessive NPHP and retinitis pigmentosa. Since mutations in the known NPHP genes collectively account for only about 30% of NPHP cases, it is possible that TMEM218 could be involved in the development of similar ciliopathies in humans. In reviewing all other reported mouse models of NPHP, we suggest that Tmem218(-/-) mice could provide a useful model for elucidating the pathogenesis of cilia-associated disease in both the kidney and the retina, as well as in developing and testing novel therapeutic strategies for Senior-Løken syndrome.