More than a marker: potential pathogenic functions of MAP2.

Microtubule-associated protein 2 (MAP2) is the predominant cytoskeletal regulator within neuronal dendrites, abundant and specific enough to serve as a robust somatodendritic marker. It influences microtubule dynamics and microtubule/actin interactions to control neurite outgrowth and synaptic functions, similarly to the closely related MAP Tau. Though pathology of Tau has been well appreciated in the context of neurodegenerative disorders, the consequences of pathologically dysregulated MAP2 have been little explored, despite alterations in its immunoreactivity, expression, splicing and/or stability being observed in a variety of neurodegenerative and neuropsychiatric disorders including Huntington's disease, prion disease, schizophrenia, autism, major depression and bipolar disorder.

MAP2 immunoreactivity deficit is conserved across the cerebral cortex within individuals with schizophrenia.

Several postmortem studies have reported lower levels of immunoreactivity (IR) for microtubule-associated protein 2 (MAP2) in several cortical regions of individuals with schizophrenia (SZ). However, whether this effect is conserved across multiple brain areas within an individual with SZ or if it is regionally-specific remains unclear. We characterized patterns of MAP2-IR across three cortical regions at different levels of the rostral-caudal axis within individual subjects with and without SZ.

Density of small dendritic spines and microtubule-associated-protein-2 immunoreactivity in the primary auditory cortex of subjects with schizophrenia.

Previously, we demonstrated that dendritic spine density (DSD) in deep layer 3 of the primary auditory cortex (A1) is 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).