title: The absence of pleiotrophin modulates gene expression in the hippocampus in vivo and in cerebellar granule cells in vitro.
abstract: Pleiotrophin (PTN) is a secreted growth factor recently proposed to act as a neuromodulatory peptide in the Central Nervous System. PTN appears to be involved in neurodegenerative diseases and neural disorders, and it has also been implicated in learning and memory. Specifically, PTN-deficient mice exhibit a lower threshold for LTP induction in the hippocampus, which is attenuated in mice overexpressing PTN. However, there is little information about the signaling systems recruited by PTN to modulate neural activity. To address this issue, the gene expression profile in hippocampus of mice lacking PTN was analyzed using microarrays of 22,000 genes. In addition, we corroborated the effect of the absence of PTN on the expression of these genes by silencing this growth factor in primary neuronal cultures in vitro. The microarray analysis identified 102 genes that are differentially expressed (z-score>3.0) in PTN null mice, and the expression of eight of those modified in the hippocampus of KO mice was also modified in vitro after silencing PTN in cultured neurons with siRNAs. The data obtained indicate that the absence of PTN affects AKT pathway response and modulates the expression of genes related with neuroprotection (Mgst3 and Estrogen receptor 1, Ers 1) and cell differentiation (Caspase 6, Nestin, and Odz4), both in vivo and in vitro.
authors.affiliation: Doctorado en Ciencias en Biología Molecular en Medicina (DCBMM), CUCS, Universidad de Guadalajara, Jalisco, Mexico.
authors.forename: Celia
authors.initials: C
authors.lastname: González-Castillo
authors.affiliation: Instituto de Investigación en Ciencias Biomédicas (IICB), CUCS, Universidad de Guadalajara, Jalisco, Mexico. Electronic address: dortuno@cucs.udg.mx.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ortuño-Sahagún
authors.affiliation: Tecnológico de Monterrey, División de Biotecnología y Salud, Escuela de Medicina, Campus Guadalajara, Jalisco, Mexico.
authors.forename: Carolina
authors.initials: C
authors.lastname: Guzmán-Brambila
authors.affiliation: Unidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco A.C., 44270 Guadalajara, Jalisco, Mexico.
authors.forename: Ana Laura
authors.initials: AL
authors.lastname: Márquez-Aguirre
authors.affiliation: Sorbonne Université UPMC UM75 INSERM U1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle Epinière, Paris, France.
authors.forename: Rita
authors.initials: R
authors.lastname: Raisman-Vozari
authors.affiliation: Department of Pharmacology and Medical Chemistry, Faculty of Pharmacy, Institute of Neuroscience (INUB), Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), University of Barcelona, Spain.
authors.forename: Mercé
authors.initials: M
authors.lastname: Pallás
authors.affiliation: Departamento de Ciencias Ambientales, Instituto de Neurociencias, CUCBA, Universidad de Guadalajara, Jalisco, Mexico. Electronic address: argelia.rojas@academicos.udg.mx.
authors.forename: Argelia E
authors.initials: AE
authors.lastname: Rojas-Mayorquín
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D053178:Caspase 6 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D016207:Cytokines / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012337:RNA, Ribosomal, 18S / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D012337:RNA, Ribosomal, 18S; D016708:Synaptophysin; C066845:pleiotrophin; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D053178:Caspase 6
keywords: AKT; Caspase 6; Cerebellar granule cells; Gene expression; Hippocampus; Neuromodulation; Pleiotrophin