title: Olfactory neurons obtained through nasal biopsy combined with laser-capture microdissection: a potential approach to study treatment response in mental disorders.
abstract: Bipolar disorder (BD) is a severe neuropsychiatric disorder with poorly understood pathophysiology and typically treated with the mood stabilizer, lithium carbonate. Animal studies as well as human genetic studies indicate that lithium affects molecular targets that are involved in neuronal growth, survival and maturation, and notably molecules involved in Wnt signaling. Given the ethical challenge to obtaining brain biopsies for investigating dynamic molecular changes associated with lithium-response in the central nervous system (CNS), one may consider the use of neurons obtained from olfactory tissues to achieve this goal.The olfactory epithelium contains olfactory receptor neurons at different stages of development and glial-like supporting cells. This provides a unique opportunity to study dynamic changes in the CNS of patients with neuropsychiatric diseases, using olfactory tissue safely obtained from nasal biopsies. To overcome the drawback posed by substantial contamination of biopsied olfactory tissue with non-neuronal cells, a novel approach to obtain enriched neuronal cell populations was developed by combining nasal biopsies with laser-capture microdissection. In this study, a system for investigating treatment-associated dynamic molecular changes in neuronal tissue was developed and validated, using a small pilot sample of BD patients recruited for the study of the molecular mechanisms of lithium treatment response.
authors.affiliation: Department of Psychiatry, Johns Hopkins University.
authors.forename: Soumya
authors.initials: S
authors.lastname: Narayan
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Howard University.
authors.forename: Charlee
authors.initials: C
authors.lastname: McLean
authors.affiliation: Department of Psychiatry, Johns Hopkins University.
authors.forename: Akira
authors.initials: A
authors.lastname: Sawa
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University.
authors.forename: Sandra Y
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Howard University.
authors.forename: Narayan
authors.initials: N
authors.lastname: Rai
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Howard University.
authors.forename: MariaMananita S
authors.initials: MS
authors.lastname: Hipolito
authors.affiliation: Department of Psychiatry, Sheppard Pratt Hospital.
authors.forename: Nicola
authors.initials: N
authors.lastname: Cascella
authors.affiliation: Department of Psychiatry, Indiana University.
authors.forename: John J I
authors.initials: JJ
authors.lastname: Nurnberger
authors.affiliation: Department of Psychiatry, Johns Hopkins University.
authors.forename: Koko
authors.initials: K
authors.lastname: Ishizuka
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Howard University; enwulia@howard.edu.
authors.forename: Evaristus A
authors.initials: EA
authors.lastname: Nwulia
mesh_terms: D000328:Adult; D001706:Biopsy; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D002469:Cell Separation; D002490:Central Nervous System / Q000187:drug effects; D005260:Female; D006801:Humans; D061346:Laser Capture Microdissection; D018020:Lithium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome; D060449:Wnt Signaling Pathway; D055815:Young Adult
chemical_list: D018020:Lithium Compounds