TY - JOUR
T1 - Olfactory neurons obtained through nasal biopsy combined with laser-capture microdissection
T2 - A potential approach to study treatment response in mental disorders
AU - Narayan, Soumya
AU - McLean, Charlee
AU - Sawa, Akira
AU - Lin, Sandra Y.
AU - Rai, Narayan
AU - Hipolito, Maria Mananita S.
AU - Cascella, Nicola
AU - Nurnberger, John J.I.
AU - Ishizuka, Koko
AU - Nwulia, Evaristus A.
N1 - Publisher Copyright:
© 2014, Journal of Visualized Experiments. All Rights Reserved.
PY - 2014/12/4
Y1 - 2014/12/4
N2 - 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.
AB - 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.
KW - Bipolar disorder
KW - GSK-3β
KW - Issue 94
KW - Laser-capture microdissection
KW - Lithium therapy
KW - Nasal biopsy
KW - Neuroscience
KW - Olfactory epithelium
KW - Real-time PCR
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U2 - 10.3791/51853
DO - 10.3791/51853
M3 - Article
C2 - 25549156
AN - SCOPUS:84917691508
SN - 1940-087X
JO - Journal of Visualized Experiments
JF - Journal of Visualized Experiments
IS - 94
M1 - e51853
ER -