Epub – Neuropsychopharmacology: Density of Small Dendritic Spines and Microtubule-Associated-Protein-2 Immunoreactivity in the Primary Auditory Cortex of Subjects with Schizophrenia

February 22, 2019

McKinney BC, MacDonald ML, Newman JT, Shelton MA, DeGiosio RA, Kelly RW, Fish KN, Sampson AR, Lewis DA, Sweet RA

Previously, we demonstrated that dendritic spine density (DSD) in deep layer 3 of the primary auditory cortex (A1) lower, due to having fewer small spines, in subjects with schizophrenia (SZ) than non- psychiatric control (NPC) subjects. We also previously demonstrated that microtubule-associated-protein-2 immunoreactivity (MAP2-IR) in A1 deep layer 3 is lower, and positively correlated with DSD, in SZ subjects. Here, we first sought to confirm these findings in an independent cohort of 25 SZ-NPC subject pairs (cohort 1). We used immunohistochemistry and confocal microscopy to measure DSD and MAP2-IR in A1 deep layer 3. Consistent with previous studies, both DSD and MAP2-IR were lower in SZ subjects. We then tested the hypothesis that MAP2-IR mediates the effect of SZ on DSD in a cohort of 45 SZ-NPC subject pairs that included all subjects from cohort 1 and two previously studied cohorts (combined cohort). Based on the distribution of MAP2-IR values in NPC subjects, we categorized each SZ subject as having either low MAP2-IR (SZ MAP2-IR(low)) or nor2mal MAP2-IR (SZ MAP2-IR(normal)). Among SZ MAP-IR(low) subjects, mean DSD was significantly lower than in NPC subjects. However, mean DSD did not differ between SZ MAP2-IR(normal) and NPC subjects. Moreover, MAP2-IR statistically mediated small spine differences, with lower MAP2-IR values associated with fewer small spines. Our findings confirm that low density of small spines and low MAP2-IR are robust SZ phenotypes and suggest that MAP2-IR mediates the effect of SZ on DSD.

McKinney BC, MacDonald ML, Newman JT, Shelton MA, DeGiosio RA, Kelly RW, Fish KN, Sampson AR, Lewis DA, Sweet RA. Density of Small Dendritic Spines and Microtubule-Associated-Protein-2 Immunoreactivity in the Primary Auditory Cortex of Subjects with Schizophrenia. Neuropsychopharm. 2019 Feb 22. doi: 10.1038/s41386-019-0350-7. [Epub ahead of print]. PubMed PMID: 30795003.

https://www.ncbi.nlm.nih.gov/pubmed/30795003

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