Circumscribed malformation and nerve cell alterations in the entorhinal cortex of schizophrenics

Abstract

A postmortem histological comparison of 5 selected cases of schizophrenia with 5 non-schizophrenic controls showed a circumscribed malformation of the entorhinal cortex. The cortical alterations consisted mainly of a lack or a change of the characteristic island formations in layer II pre-alpha. Further, there were atypical neurons in layers II and III showing a conspicuous decrease of volume, often a change of the shape. They lay either in clusters or in columnar formations. These cells were considered "young neurons". The changes varied considerably from case to case and sometimes extended to all entorhinal layers. In one case the extension of the changes is described by means of serial sections in steps which extend over the whole rostral entorhinal region. Here, the striking architectural changes were formed in an exactly circumscribed sector and did not extend to the rostral hippocampal formation. On the whole, the changes are regarded as local migrational disturbances that occur during the second trimester of brain development. Neuronal displacements like these could give rise to various aberrant connections within the limbic system and related structures (e.g. the central position of the entorhinal region in circuits such as the entorhino-hippocampal loop, entorhinol-insula and entorhino-orbitofrontal reciprocal connections). Whereas alterations of the genetic programming of cell migrations may be suspected, various environmental influences (e.g. viral infections during the months III-V of pregnancy) appear to play a significant role. The malformations may be a decisive vulnerability factor for the later manifestation of the illness.

Excitatory Actions of NMDA Receptor Antagonists in Rat Entorhinal Cortex and Cultured Entorhinal Cortical Neurons

“…Thus, these excitatory alterations could be used to delineate the neuronal circuits that, when functioning abnormally, produce psychotic behavior. Because of the important role of the EC in the processing of sensory input (Jones 1993) and disturbances in the neuronal organization and activity repeatedly observed in the EC neurons in schizophrenic brains (Falkai et al 1988;Arnold et al 1991;Bogerts 1993;Jakob and Beckmann 1994;Silbersweig et al 1995), caudal EC is a strong candidate for the brain area that is affected in schizophrenia. The relatively large number of affected neurons in the cEC and the wealth of information concerning the connectivity and physiology of the entorhinal-hippocampal system render this brain area a good candidate for a model system.…”

“…Analysis of post-mortem material have suggested that brains of schizophrenic patients may display cytoarchitectonic disturbances in the entorhinal cortex (Falkai et al 1988;Arnold et al 1991;Bogerts 1993;Jakob and Beckmann 1994). CT scans of brains of schizophrenic patients have consistently demonstrated loss of gray matter in parahippocampal gyrus (Roberts 1990).…”

Total number, distribution, and phenotype of cells expressing chondroitin sulfate proteoglycans in the normal human amygdala

“…We note that CSPG functions may bear direct relevance to the pathophysiology of this disease. For instance, in schizophrenic subjects, disruptions of cell migration and abnormal numbers of axon fibers, suggestive of a disruption of axonal guidance, may be related to altered CSPG expression (Akbarian, et al, 1996, Arnold, et al, 1991, Falkai, et al, 2000, Jakob, et al, 1986, Jakob, et al, 1994, Kovalenko, et al, 2003, Longson, et al, 1996. Direct functional interactions between neurotransmitters known to be involved in this disorder, such as glutamate and GABA, and CSPGs have been described by several authors (Dityatev, et al, 2007, Schwarzacher, et al, 2006.…”

Cytokine and growth factor involvement in schizophrenia—support for the developmental model

“…17 Moreover, disorientation of pre-alpha cells in layer II of the entorhinal cortex suggests a problem with embryonic neuroblast migration and/or differentiation. 11,20,21 More detailed pathological information and discussion are available in recent reviews. [22][23][24] What could cause such abnormalities during development?…”