title: Decreased Lin7b expression in layer 5 pyramidal neurons may contribute to impaired corticostriatal connectivity in huntington disease.
abstract: Motor dysfunction, cognitive impairment, and regional cortical atrophy indicate cerebral cortical involvement in Huntington disease (HD). To address the hypothesis that abnormal corticostriatal connectivity arises from polyglutamine-related alterations in cortical gene expression, we isolated layer 5 cortical neurons by laser-capture microdissection and analyzed transcriptome-wide mRNA changes in them. Enrichment of transcription factor mRNAs including foxp2, tbr1, and neuroD6, and neurotransmission- and plasticity-related RNAs including sema5A, pclo, ntrk2, cntn1, and Lin7b were observed. Layer 5 motor cortex neurons of transgenic R6/2 HD mice also demonstrated numerous transcriptomic changes, including decreased expression of mRNAs encoding the Lin7 homolog b ([Lin7b] also known as veli-2 and mals2). Decreases in LIN7B and CNTN1 RNAs were also detected in human HD layer 5 motor cortex neurons. Lin7 homolog b, a scaffold protein implicated in synaptic plasticity, neurite outgrowth, and cellular polarity, was decreased at the protein level in layer 5 cortical neurons in R6/2 mice and human HD brains. Decreases in Lin7b and Lin7a mRNAs were detected in R6/2 cortex as early as 6 weeks of age, suggesting that this is an early pathogenetic event. Thus, decreased cortical LIN7 expression may contribute to abnormal corticostriatal connectivity in HD.
authors: Department of Neurology, University Hospital Freiburg, Freiburg, Germany.
authors: Birgit
authors: B
authors: Zucker
authors: Jibrin A
authors: JA
authors: Kama
authors: Alexandre
authors: A
authors: Kuhn
authors: Doris
authors: D
authors: Thu
authors: Lianna R
authors: LR
authors: Orlando
authors: Anthone W
authors: AW
authors: Dunah
authors: Ozgun
authors: O
authors: Gokce
authors: David M
authors: DM
authors: Taylor
authors: Johann
authors: J
authors: Lambeck
authors: Bernd
authors: B
authors: Friedrich
authors: Katrin S
authors: KS
authors: Lindenberg
authors: Richard L M
authors: RL
authors: Faull
authors: Cornelius
authors: C
authors: Weiller
authors: Anne B
authors: AB
authors: Young
authors: Ruth
authors: R
authors: Luthi-Carter
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000473:pathology / Q000502:physiology; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000473:pathology / Q000503:physiopathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D046228:Microarray Analysis; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C486532:LIN7A protein, human; C114671:LIN7B protein, human; C114670:Lin7a protein, mouse; C485432:Lin7b protein, mouse; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins