Year: 2009
Type: dissertation
Abstract: Neurons within the peripheral nervous system (PNS) have a remarkable ability to repair themselves after injury; however, neurons within the central nervous system (CNS) do not spontaneously regenerate.Therefore, understanding the molecular elements responsible for successful regenerative response in the PNS can help us to establish basic principles and strategies for promoting regeneration in CNS structures such as the spinal cord.Nerve repair in the PNS has been suggested to be in part due to the involvement of intrinsic molecules such as transcription factors.In this thesis, I am focusing on the C/EBP family of transcription factors and their potential role in axonal regeneration after PNS injury.I examined the expression of different C/EBP members in PNS after injury after, using the sciatic nerve crush injury model I found that C/EBPδ mRNA is upregulated 4, 24 and 72 hours in dorsal root ganglia (DRG) following injury, whereas C/EBPβ and C/EBPγ expression is transiently upregulated by 4 hours resuming background levels after 72 hours.Conversely, C/EBPα and C/EBPε did not show upregulation following injury.In order to determine the function of C/EBPs in axonal growth in an in vitro system I used the ND7/23 cell line where I found that upon neurite growth induced by cyclic adenosine monophosphate (cAMP), the mRNA levels of C/EBPβ and C/EBPδ were upregulated.Furthermore, the conditional expression of a C/EBP total inhibitor or a C/EBPδ antisense construct decreases neurite elongation in vitro.Additionally, I found that 24 hours after treatment of ND7/23 cells with trichostatin A (TSA) C/EBPδ expression is elevated.Subsequently, I found that in DRG cultures from C/EBPδ knock-out animals, the lack of C/EBPδ affects the intrinsic growth capacity of dorsal root ganglion neurons which show a List of abbreviations Arg-1 Arginase-1 AP-1 Activator protein-1 ATF Activating transcription factor Bcl-2 B cell lymphoma leukaemia 2 protein BDNF Brain-derived neurotrophic factor bHLH Basic helix-loop helix cAMP Cyclic adenosine3'-5' monophosphate CAP-23 Cytoskeleton associated protein-23 C/EBP CCAT-enhancer binding protein CBP CREB binding protein CGRP Calcitonin gene-related peptide Chip Chromatin immunoprecipitation CHOP C/EBP Homologous Protein CNS Central nervous system CNTF Ciliary neurotriphic factor CRE cAMP response element CREB cAMP responsive element binding protein CS-PG Chondroitin sulphate proteoglycans CT-1 Cardiotrophin-1 dbcAMP Dibutyryl cAMP DMEM Dulbeco's modified eagles media DREZ Dorsal root entry zone DRG Dorsal root ganglia EDTA Ethylene disodium tetra acetate EGF Epidermal growth factor ERK Extracellular signal regulated kinase FBS Fetal Bovine Serum FGF Fibroblast growth factor GAG Glycosaminoglycan GAP-43 Growth associated protein-43 GDNF Glial-derived neurotrophic factor GFAP Glial fibrillary acidic protein gp130 glycoprotein 130 HAT Histone acetyltransferase HBSS Hanks balanced salt solution HDAC Histone deacetylases HNF Hepatocyte nuclear factor IFN Interferon IL Interleukin JAK Janus kinase JNK Jun N-terminal Kinase kDa Kilodalton LIF Leukaemia inhibitory factor LPS Lipopolysaccharide LRR Leucine rich repeat LTM Long term memory MAG Myelin associated glycoprotein MAP
Author: Luís Heredia
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W841828945