Wild-type microglia do not reverse pathology in mouse models of Rett syndrome.

Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by mutations in the X chromosomal gene () (1). RTT treatment so far is symptomatic. disruption in mice phenocopies major features of the syndrome (2) that can be reversed upon re-expression of (.

Discovery of a neuroprotective chemical, (S)-N-(3-(3,6-dibromo-9H-carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin-2-amine [(-)-P7C3-S243], with improved druglike properties.

(-)-P7C3-S243 is a neuroprotective aminopropyl carbazole with improved druglike properties compared with previously reported compounds in the P7C3 class. It protects developing neurons in a mouse model of hippocampal neurogenesis and protects mature neurons within the substantia nigra in a mouse model of Parkinson's disease. A short, enantioselective synthesis provides the neuroprotective agent in optically pure form.

Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of amyotrophic lateral sclerosis.

We previously reported the discovery of P7C3, an aminopropyl carbazole having proneurogenic and neuroprotective properties in newborn neural precursor cells of the hippocampal dentate gyrus. We have further found that chemicals having efficacy in this in vivo screening assay also protect dopaminergic neurons of the substantia nigra following exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a mouse model of Parkinson disease. Here, we provide evidence that an active analog of P7C3, known as P7C3A20, protects ventral horn spinal cord motor neurons from cell death in the G93A-SOD1 mutant mouse model of amyotrophic lateral sclerosis (ALS).

Tumor necrosis factor is critical for cytolytic T cell activity against allospecific hepatocytes and splenic targets in major histocompatibility complex class I disparate graft versus host disease.

The present studies determined the role of tumor necrosis factor (TNF)/tumor necrosis factor receptor (TNFR) interactions on cytolytic (CTL) activity of splenic and intrahepatic lymphocytes (IHL) isolated from mice undergoing graft versus host disease, induced by transfer of B6 T cells to major histocompatibility complex (MHC) class I disparate bm1 × B6 F1 mice. Allospecific killing of anti-H-2(bm1) splenic and hepatocyte targets was assessed by 4-h (51)Cr release and 16-h DNA lysis assays, respectively, utilizing spleen cells (SpC) and IHL isolated (1) from sublethally irradiated bm1 × B6 F1 who had received B6 spleen and bone marrow cells, and a control adenovirus (Adv-βgal) or a TNF inhibitor expressing adenovirus (Adv-TNFi), or (2) from bm1 × B6 F1 recipients of B6, B6.129-Tnfrsf1a(tm1Mak)/J (TNFR1(-/-)), B6.