However, little is known about reelin’s role for behavioral and cognitive functions in vivo. Therefore, the effect of a reelin knockdown in the medial prefrontal cortex (mPFC) of Wistar rats was examined in behavioral tasks related to neuropsychiatric disorders, such as schizophrenia. Rats treated with reelin antisense phosphothioate oligonucleotides in the mPFC during puberty or adulthood

were tested for prepulse inhibition (PPI) of Navitoclax research buy the acoustic startle reflex, spatial working memory, object recognition, and locomotor activity. Reelin quantification in the mPFC was assessed by Western blotting. Local reelin knockdown during puberty or adulthood induced (1) a PPI deficit as well as (2) an impairment of spatial

working memory and object recognition following pubertal injections. Western blot analyses showed a distinct and highly selective reelin knockdown in the rats’ mPFC. These results indicate that mPFC reelin signaling plays an important role in behavioral tasks with relevance to e.g. schizophrenia. Understanding selleck chemical reelin’s function as a neurotrophic modulator of the extracellular matrix may help to achieve new insights into the etiology of certain neuropsychiatric diseases and foster prospective treatment strategies. (C) 2011 Elsevier Inc. All rights reserved.”
“Background: The BCR-ABL1 translocation occurs in chronic myeloid leukemia (CML) and in 25% of cases with acute lymphoblastic leukemia (ALL). The advent of tyrosine kinase inhibitors (TKI) has fundamentally changed the treatment of CML. However, TKI are not equally effective for treating ALL. Furthermore, de novo or secondary TKI-resistance is a significant problem in CML. We screened a

panel of BCR-ABL1 positive ALL and CML cell lines to find models for imatinib-resistance.\n\nResults: Five of 19 BCR-ABL1 positive cell lines were resistant to imatinib-induced apoptosis (KCL-22, MHH-TALL1, NALM-1, SD-1, find more SUP-B15). None of the resistant cell lines carried mutations in the kinase domain of BCR-ABL1 and all showed resistance to second generation TKI, nilotinib or dasatinib. STAT5, ERK1/2 and the ribosomal S6 protein (RPS6) are BCR-ABL1 downstream effectors, and all three proteins are dephosphorylated by imatinib in sensitive cell lines. TKI-resistant phosphorylation of RPS6, but responsiveness as regards JAK/STAT5 and ERK1/2 signalling were characteristic for resistant cell lines. PI3K pathway inhibitors effected dephosphorylation of RPS6 in imatinib-resistant cell lines suggesting that an oncogene other than BCR-ABL1 might be responsible for activation of the PI3K/AKT1/mTOR pathway, which would explain the TKI resistance of these cells. We show that the TKI-resistant cell line KCL-22 carries a PI3K alpha E545G mutation, a site critical for the constitutive activation of the PI3K/AKT1 pathway.