title: Proteomics of rat hypothalamus, hippocampus and pre-frontal/frontal cortex after central administration of the neuropeptide PACAP.
abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that exerts pleiotropic functions, acting as a hypophysiotropic factor, a neurotrophic and a neuroprotective agent. The molecular pathways activated by PACAP to exert its physiological roles in brain are incompletely understood. In this study, adrenocorticotropic hormone (ACTH), prolactin, luteinising hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), brain-derived neurotrophic factor and corticosterone blood levels were determined before and 20, 40, 60, and 120 min after PACAP intracerebroventricular administration. PACAP treatment increased ACTH, corticosterone, LH and FSH blood concentrations, while it decreased TSH levels. A proteomics investigation was carried out in hypothalamus, hippocampus and pre-frontal/frontal cortex (P/FC) using 2-dimensional gel electrophoresis at 120 min, the end-point suggested by studies on PACAP hypophysiotropic activities. Spots showing statistically significant alterations after PACAP treatment were identified by Matrix-assisted laser desorption/ionization-Time of flight mass spectrometry. Identified proteins were consistent with PACAP involvement in different molecular processes in brain. Altered expression levels were observed for proteins involved in cytoskeleton modulation and synaptic plasticity: actin in the hypothalamus; stathmin, dynamin, profilin and cofilin in hippocampus; synapsin in P/FC. Proteins involved in cellular differentiation were also modulated: glutathione-S-transferase α and peroxiredoxin in hippocampus; nucleoside diphosphate kinase in P/FC. Alterations were detected in proteins involved in neuroprotection, neurodegeneration and apoptosis: ubiquitin carboxyl-terminal hydrolase isozyme L1 and heat shock protein 90-β in hypothalamus; α-synuclein in hippocampus; glyceraldehyde-3-phosphate dehydrogenase and prohibitin in P/FC. This proteomics study identified new proteins involved in molecular mechanisms mediating PACAP functions in the central nervous system.
authors.affiliation: Neurosciences CEDD, GlaxoSmithKline Medicines Research Centre, Via A Fleming 4, 37135 Verona, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Gasperini
authors.forename: Chiara
authors.initials: C
authors.lastname: Piubelli
authors.forename: Lucia
authors.initials: L
authors.lastname: Carboni
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood; D003345:Corticosterone / Q000097:blood; D015180:Electrophoresis, Gel, Two-Dimensional; D005640:Follicle Stimulating Hormone / Q000097:blood; D005625:Frontal Lobe / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood; D040901:Proteomics / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000235:genetics* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013972:Thyrotropin / Q000097:blood; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D003345:Corticosterone