engleski

Increased axon staining of prefrontal pyramidal neurons in schizophrenia: A Golgi study

Pyramidal neuron is a principal cell of the cerebral cortex characterized by long projecting axon, rich local axon arborization and specific topology of dendrites covered by high number of dendritic spines. Around 70% of cortical synapses are excitatory glutamatergic located on dendritic spines, with the major source from cortical pyramidal neurons local branches. In human infant, huge growth of corticocortical fibers is present during perinatal period, and later on excitatory intracortical circuitry develops. They form dendritic spine synapses that are overproduced and undergo pruning during childhood and puberty. Dendritic spine synapse loss that occurs during adolescence is the final step in cortical circuitry developmental reorganization. At that age symptoms of schizophrenia become expressed suggesting that this might be a result of disturbed circuitry reorganization. The lesion might even date to fetal life, but protracted cortical circuitry maturation makes it silent until adolescence. Quantitative analysis was performed using Golgi impregnated slices taken from the prefrontal cortex of 5 schizophrenic patients (average age 54 years) and 5 subjects without signs and history of neurological and psychiatric diseases (average age 58 years). All specimens were part of the Zagreb Neuroembryological Collection. Axon arborization of all pyramidal neurons from randomly chosen areas through all cortical layers was three-dimensionally reconstructed using Neurolucida 3.18 software. Obtained data were quantitatively analyzed and finally statistically processed. The majority of impregnated cells in that areas were large and medium large pyramidal neurons situated in the lower half of layers III and V that showed qualitatively increased axon staining in schizophrenic subjects compared to control group. Quantitative data showed that the average length of impregnated axon of schizophrenic patients was three times higher than in control group and the number of bifurcations were also significantly higher. Basal and average diameter of primary axon segment did not differ statistically between schizophrenia and control group indicating that no major ultrastructural pathology was present in axon of pyramidal neuron. The main difference between schizophrenic and control subjects was present in the early adult age, and differences between two groups diminished with aging. Immature pyramidal neurons impregnated by Golgi method are characterized by extensive axon staining that decreased during early postnatal period, possibly as a result of increased myelinization and axon neurofilament maturation. In adult subjects without neurological and psychiatric background only very short axon initial segment (around 10-20 micron in length) was impregnated on majority of pyramidal cells. Observed increased axon staining on prefrontal pyramidal neurons in schizophrenic persons could be a result of disturbance in neurofilamentous maturation, sign of axon growth or insufficient axon elimination. Increased vertical glutamatergic fiber staining was described in schizophrenic persons in entorhinal cortex and superficial laminas of the cingulate cortex. Taken together these results support the hypothesis of schizophrenia as a disease of cortical circuitry disorganization, principally connected with fronto-limbic pathway.

cognitive functions; development; adolescence

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