Higher levels of α7 nicotinic receptors, but not choline acetyltransferase, in the dorsolateral prefrontal cortex from a sub-group of patients with schizophrenia

Abstract

It has been suggested the study of sub-groups within the syndrome of schizophrenia will assist in elucidating the complex pathophysiology of the syndrome. Hence, we have studied a number of cholinergic markers in the cortex from a sub-group of subjects with schizophrenia that have a marked decrease in levels of muscarinic M1 receptors (MRDS). The displacement of [³H]NMS by cortical extracts was used to measure tissue anticholinergic load, [¹²⁵I]α bungarotoxin binding was used to measure levels of the α7 nicotinic receptor (CHRNA7) and western blotting was used to measure levels of choline acetyltransferase (ChAT) 68 and 82 as well as synaptosome nerve-associated protein 25 (SNAP25). In comparing schizophrenia, MRDS and non-MRDS to controls, there were no differences in levels of ChAT 68 or 82, SNAP 25 or cholinergic load in BA 9. However, levels of CHRNA7 were higher in BA 9, but not BA 6 or 44, from subjects with MRDS. These data argue that there is no change in cholinergic innovation (measured using ChAT), presynaptic neurons (measured using SNAP25) or cholinergic load in schizophrenia, MRDS or non-MRDS. However, increased levels of CHRNA7 may be contributing to a breakdown in cholinergic homeostasis in BA 9, but not BA 6 or 44, in subjects with MRDS.

Keywords: Choline acetyltransferase; Cholinergic load; Cortex; Cotinine; Schizophrenia; α7 nicotinic receptor.