title: Microdissection and transcriptional profiling: a window into the pathobiology of preclinical prion disease.
abstract: Prion diseases share common features on a sub-cellular level with many neurodegenerative diseases including Alzheimer disease; the most prevalent neurodegenerative disease world-wide. The most obvious similarity is the accumulation of misfolded forms of the host proteins which forms aggregates in the brains of patients. Remarkably, one of the earliest pathological changes detected in degenerating brain tissue, well before clinical symptoms are observed, is synaptic dysfunction and loss. This pathology was recently shown to be reversible in early stages of mouse prion disease suggesting that synaptic regeneration and reestablishment of neuronal function is possible. Determination of the molecular events that underlie synapse degeneration and how this eventually results in neuronal loss is therefore a research priority that may contribute to the search for new therapeutic interventions for neurodegenerative disorders. Functional genomic studies using unbiased whole genome expression analyses represent one method that can provide insights into these perplexing processes. However, transcriptional profiles from brain tissues are representative of a heterogeneous mixture of cell types that effectively mask the expression of low abundance transcripts, or molecular changes that occur only in a small population of affected neurons. One method that was recently applied to address these challenges was laser capture microdissection which was used to effectively isolate the CA1 neuronal rich region of the hippocampus prior to RNA extraction. Profiling of both mRNAs and microRNAs revealed previously unidentified neuronal-specific genes and expression signatures that are relevant to understanding the pathophysiological processes involved in preclinical stages of prion disease. In this review we will highlight these molecular signatures and discuss their implications with respect to prion-induced neurodegeneration.
authors.forename: Anna
authors.initials: A
authors.lastname: Majer
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Booth
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D042282:Microdissection; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D017096:Prion Diseases / Q000235:genetics / Q000473:pathology*; D014158:Transcription, Genetic
chemical_list: D035683:MicroRNAs