α7 nicotinic acetylcholine receptor, activated glia, and cognitive impairment in schizophrenia: a dual-tracer PET...

The α7 nicotinic acetylcholine receptor (nAChR) plays a crucial role in cognitive function, and its dysfunction has been proposed as a primary pathophysiological factor in schizophrenia. Although the α7 nAChR is expressed in both neuronal and activated glial cells, its association with activated glia and its role in the pathophysiology of schizophrenia remain uncertain. Therefore, we investigated α7 nAChR availability and activated glia evaluated with 18 kDa translocator protein (TSPO) levels in individuals with schizophrenia, and further examined their association and relationships to cognitive impairment. Nineteen individuals with schizophrenia, no smoking history or use of anticholinergic or benzodiazepine medications for at least 6 months, and 20 age- and sex-matched healthy controls underwent [¹¹C](R)-MeQAA and [¹¹C]DPA713 positron emission tomography scans on the same day. Whole-brain analyses revealed significantly higher α7 nAChR availability in the right cerebellum, perihippocampal region, putamen, and occipital cortex in individuals with schizophrenia. In line with previous findings, TSPO levels did not differ between groups. Furthermore, in the schizophrenia group, elevated α7 nAChR availability was significantly positively correlated with TSPO levels and letter fluency performance in various brain regions predominantly in the right hemisphere. Notably, in the right perihippocampal region, there was an overlap in regions showing a significantly higher α7 nAChR availability and regions significantly correlated with activated glia and cognitive dysfunction. Our findings provide novel insights into the role of the α7 nAChR and its association with activated glia in schizophrenia, and the α7 nAChR may serve as a potential therapeutic target for cognitive dysfunction.