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Toronto, Canada

Merenlender-Wagner A.,Tel Aviv University | Malishkevich A.,Tel Aviv University | Shemer Z.,Tel Aviv University | Udawela M.,University of Melbourne | And 9 more authors.
Molecular Psychiatry | Year: 2015

Autophagy is a process preserving the balance between synthesis, degradation and recycling of cellular components and is therefore essential for neuronal survival and function. Several key proteins govern the autophagy pathway including beclin1 and microtubule associated protein 1 light chain 3 (LC3). Here, we show a brain-specific reduction in beclin1 expression in postmortem hippocampus of schizophrenia patients, not detected in peripheral lymphocytes. This is in contrast with activity-dependent neuroprotective protein (ADNP) and ADNP2, which we have previously found to be deregulated in postmortem hippocampal samples from schizophrenia patients, but that now showed a significantly increased expression in lymphocytes from related patients, similar to increases in the anti-apoptotic, beclin1-interacting, Bcl2. The increase in ADNP was associated with the initial stages of the disease, possibly reflecting a compensatory effect. The increase in ADNP2 might be a consequence of neuroleptic treatment, as seen in rats subjected to clozapine treatment. ADNP haploinsufficiency in mice, which results in age-related neuronal death, cognitive and social dysfunction, exhibited reduced hippocampal beclin1 and increased Bcl2 expression (mimicking schizophrenia and normal human aging). At the protein level, ADNP co-immunoprecipitated with LC3B suggesting a direct association with the autophagy process and paving the path to novel targets for drug design. © 2015 Macmillan Publishers Limited All rights reserved 1359-4184/15. Source

Soreni N.,Psychiatry Research Unit | Soreni N.,Brain Body Institute | Noseworthy M.D.,Brain Body Institute | Noseworthy M.D.,McMaster University | And 4 more authors.
Journal of Magnetic Resonance Imaging | Year: 2010

Purpose: To measure interindividual, repositioning, and time-of-day effects of single voxel PRESS (Point RESolved Spectroscopy) proton magnetic resonance spectroscopy ( 1H-MRS) acquisition of the anterior cingulate cortex (AC) in healthy human subjects. Materials and Methods: AC 1H-MRS measurements were performed in 15 healthy adult volunteers using a short echo PRESS sequence (GE Healthcare 3 Tesla, TE/TR = 30/2500 ms, 192 acquisitions, 6 cm 3 voxels). For each individual, a total of eight spectra were obtained during two identical scanning sessions separated by 3.5 h. In each, two consecutive AC spectra were acquired. After the first two scans, the subject left the scanner, then immediately returned for repositioning and acquisition of two more consecutive spectra. The subject then left the imaging centre to return 3.5 h later for a repeated procedure. Spectroscopic postprocessing was done using LCmodel. Interindividual, repositioning and time-of-day effects were measured using restricted maximum likelihood (REML) models of variance components analysis, where response variables were levels of creatine/phosphocreatine (Cr), N-acetyl-aspartate (NAA), myo-inositol (mI), choline (Cho), and the glutamate-glutamine complex (Glx). Results: Interindividual effects were markedly higher than time-of-day and repositioning effects for all metabolites. Conclusion: Our findings show that 1H-MRS measurements of the AC are sensitive to interindividual differences, while time of day and repositioning are markedly less important. © 2010 Wiley-Liss, Inc. Source

Damri O.,Psychiatry Research Unit | Damri O.,Ben - Gurion University of the Negev | Damri O.,Mental Health Center | Sade Y.,Psychiatry Research Unit | And 14 more authors.
European Neuropsychopharmacology | Year: 2015

We have previously shown that homozygote knockout (KO) of inositol-monophosphatase1 (IMPA1) results in lithium (Li)-like behavior. We now aimed to find out whether Li-treated mice and IMPA1 KO mice exhibit neurochemical similarity at the gene- and protein-expression level. Hippocampal and frontal cortex B-cell lymphoma (Bcl-2), Bcl-2-associated X protein (BAX), P53, Perodoxin2 (PRDX2), myristoylated alanine-rich C kinase substrate (MARCKS) and neuropeptide Y (NPY) mRNA levels, and hippocampal, frontal cortex and hypothalamic cytokine levels, all previously reported to be affected by lithium treatment, were measured in three groups of mice: wildtype (WT) on regular-food (RF), WT on Li-supplemented food (Li-treated) and IMPA1-KOs.Hippocampal and frontal cortex Bcl-2 and MARCKS were the only genes commonly affected (downregulated) by Li and IMPA1 KO; Bcl-2 - by 28% and 19%, respectively; MARCKS - by about 20% in both regions.The effect of Li and of IMPA1 KO on cytokine levels differed among the three brain areas studied. Only in the hippocampus both interventions exerted similar effects. Frontal cortex cytokine levels were unaffected neither by Li nor by IMPA1 KO.Similar changes in Bcl-2 and MARCKS but not in PRDX2 and NPY following both Li-treatment and IMPA1 KO suggest a mechanism different than inositol-monophosphatase1 inhibition for Li[U+05F3]s effect on the latter genes. The cytokine levels results suggest that the mechanism mediating Li[U+05F3]s effect on the inflammatory system differs among brain regions. Only in the hippocampus the results favor the involvement of the phosphatidylinositol (PI) cycle. © 2014 Elsevier B.V. and ECNP. Source

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