title: A micro-silicon chip for in vivo cerebral imprint in monkey.
abstract: Access to cerebral tissue is essential to better understand the molecular mechanisms associated with neurodegenerative diseases. In this study, we present, for the first time, a new tool designed to obtain molecular and cellular cerebral imprints in the striatum of anesthetized monkeys. The imprint is obtained during a spatially controlled interaction of a chemically modified micro-silicon chip with the brain tissue. Scanning electron and immunofluorescence microscopies showed homogeneous capture of cerebral tissue. Nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) analysis of proteins harvested on the chip allowed the identification of 1158 different species of proteins. The gene expression profiles of mRNA extracted from the imprint tool showed great similarity to those obtained via the gold standard approach, which is based on post-mortem sections of the same nucleus. Functional analysis of the harvested molecules confirmed the spatially controlled capture of striatal proteins implicated in dopaminergic regulation. Finally, the behavioral monitoring and histological results establish the safety of obtaining repeated cerebral imprints in striatal regions. These results demonstrate the ability of our imprint tool to explore the molecular content of deep brain regions in vivo. They open the way to the molecular exploration of brain in animal models of neurological diseases and will provide complementary information to current data mainly restricted to post-mortem samples.
authors.affiliation: Institut des Neurosciences Team 7 Brain Nanomedicine, INSERM U836, UJF, CHU, Grenoble, France. zaccaria.affif@gmail.com
authors.forename: Affif
authors.initials: A
authors.lastname: Zaccaria
authors.forename: Ali
authors.initials: A
authors.lastname: Bouamrani
authors.forename: Laurent
authors.initials: L
authors.lastname: Selek
authors.forename: Michelle
authors.initials: M
authors.lastname: El Atifi
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Hesse
authors.forename: Aurélie
authors.initials: A
authors.lastname: Juhem
authors.forename: David
authors.initials: D
authors.lastname: Ratel
authors.forename: Herve
authors.initials: H
authors.lastname: Mathieu
authors.forename: Yohann
authors.initials: Y
authors.lastname: Coute
authors.forename: Christophe
authors.initials: C
authors.lastname: Bruley
authors.forename: Jerome
authors.initials: J
authors.lastname: Garin
authors.forename: Alim L
authors.initials: AL
authors.lastname: Benabid
authors.forename: Stephan
authors.initials: S
authors.lastname: Chabardes
authors.forename: Brigitte
authors.initials: B
authors.lastname: Piallat
authors.forename: François
authors.initials: F
authors.lastname: Berger
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D003342:Corpus Striatum / Q000502:physiology* / Q000648:ultrastructure; D018392:Genomic Imprinting / Q000502:physiology*; D000882:Haplorhini; D008252:Macaca fascicularis; D009043:Motor Activity / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D040901:Proteomics / Q000379:methods; D012825:Silicon; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D012825:Silicon