The alpha 7-nicotinic acetylcholine receptor and the pathology of hippocampal interneurons in schizophrenia

This paper is a review of a recent findings on the pathology of hippocampal interneurons in schizophrenia, with specific emphasis on a protein express ed by these cells, the alpha7-nicotinic acetylcholine receptor subunit. Con vergent information indicates that interneurons in the hippocampus and othe r forebrain structures are decreased in number and function in subjects wit h schizophrenia. Among the neurochemical markers that are decreased in the hippocampus are synapsin I, cholecystokinin, somatostatin, glutamic acid de carboxylase, and nitric oxide synthase. GABA uptake sites and the GABA synt hetic enzyme glutamic acid decarboxylase are also diminished. Included amon g these findings is decreased binding of alpha -bungarotoxin, which binds t o low-affinity nicotinic acetylcholine receptors, such as the alpha -nicoti nic receptor. Co-labeling experiments in rodents indicate that these marker s are expressed on overlapping populations of hippocampal interneurons. Thu s. the finding of decreased neurochemical function of hippocampal interneur ons is a widely replicated finding, with different groups reporting markedl y similar findings using independent post mortem samples and different neur ochemical strategies. Decreased alpha -bungarotoxin binding or decreased al pha7-nicotinic receptor immunoreactivity has also been found in the frontal cortex and in the nucleus reticularis thalami of schizophrenic subjects. T he alpha7-nicotinic receptor subunit gene on chromosome 15q14 is a site of heritability for schizophrenia and bipolar affective disorder, and in, part icular, for a deficit in inhibitory neuronal function associated with these illnesses. Thus, the post mortem data are further supported by psychophysi ologic and genetic investigations that indicate a deficit in inhibitory int erneuronal function, involving the alpha7-nicotinic receptor. The alpha7-re ceptor is a ligand-gated ion channel that admits calcium ions into cells, a nd it has been proposed to have various developmental roles. Its malfunctio n may be part of the developmental pathogenesis of schizophrenia. (C) 2000 Elsevier Science B.V. All rights reserved.