Alterations in hippocampal mossy fiber pathway in Schizophrenia and Alzheimer' s disease

Abstract

Schizophrenia and Alzheimer's disease (AD) both involve pathology of the medial temporal lobe. Structural abnormalities of the entorhinal cortex (Arnold et al 1991a; Arnold et al 1991b) and behavioral deficits implicating medial temporal circuits (Saykin et al 1991) have been reported in schizophrenia. The entorhinal cortex is the first and among the most severely effected regions in AD (Braak and Braak 1992). The entorhinal cortex receives input from higher-order multimodal and sensory-specific association cortices and transmits that information to the hippocampus via its connections with the dentate gyrus (Rosene an Van Hoesen 1987). The memory deficit in AD has been related to the disruption of this connection to the hippocampus, the perforant pathway (Hyman et al 1984). Despite the strong evidence of neuropathological changes in the entorhinal cortex in AD and schizophrenia, it is not known if they result in transneuronal changes of intrahippocampal connections. One method for testing this is to examine whether the density of mossy fibers, arising from the granule cells of the dentate gyrus and innervating the hilus, CA4 and CA3 subfields of the hippocampus (Rosene and Van Hoesen 1987), is altered. Experimentally induced unilateral entorhinal lesions lead to sprouting of the hippocampal mossy fibers (Steward 1992). Examination of the density of mossy fibers arising from the dentate granule cells has not been previously report4ed for these two diseases. We examined the staining intensity of the mossy fibers, following