- Email: [email protected]
Ultrastructural markers of cell membrane abnormalities in postmortem schizophrenic brain
110
A. 180. U L T R A S T R U C T U R A L ALTERATIONS OF GLUTAMATERGIC MOSSY FIBER SYNAPSES IN POSTMORTEM HIPPOCAMPUS OF SCHIZOPHRENICS N.S. Kolomeets, V.I. R a c h m a n o v a , D.D. Orlovskaya, N.A. U r a n o v a
Laboratory of Clinical Neuropathology, Mental Health Research Center, Zagor odnoe sh.2-2, Moscow, 113152, Russia The mossy fibers (MF), which are the axons of the granular cells of the dentate gyrus, use glutamate as a neurotransmitter, contain zinc, peptides and GABA. The MF have been associated with memory and special learning functions. It has been shown that the MF form giant terminals (MFT) to be in synaptic contacts mostly with branched dendritic spines of the pyramidal neurons in the CA3 region of the hippocampus. Qualitative and quantitative electron microscopic study of the MF synapses in the stratum lucidum of the CA3 region of the hippocampus was performed in 7 normal controls and 7 agematched chronic schizophrenics (postmortem delay 4-7 hours). Qualitative study showed a clumping of synaptic vesicles in part of MFT and a few dark degenerating MFT in schizophrenic brains compared to controls. Quantitative study demonstrated that 5 schizophrenic cases with predominantly positive symptoms differed significantly from controls by a reduction in total area and number of invaginated spines per MFT (p<0.01) and in the number of postsynaptic spines per MFT (p=0.012). No effects of postmortem delay, age, neuroleptic exposure were found. These preliminary data are consistent with the data about the reduction in regional zinc staining in postmortem hippocampus from schizophrenic patients (Goldsmith and Joyce, 1995) and suggest a hypofunction of MF synapses in some chronic schizophrenics. Supported by the Theodore and Vada Stanley Foundation.
R~/erences 1. S.K. Goldsmith, J.N. Joice (1995). Biol. Psychiatry 37, 2: 122 127.
A. 181. U L T R A S T R U C T U R A L MARKERS OF CELL MEMBRANE ABNORMALITIES IN POSTMORTEM SCHIZOPHRENIC BRAIN N.A. U r a n o v a , D.D. Orlovskaya, I.S. Zimina, O.V. Vikhreva, V.I. R a c h m a n o v a
Laboratory qf Clinical Neuropathology, Mental Health Research Center, Zagorodnoe sh.2-2, Moscow, 113152, Russ'ia Abnormalities of cell membranes with the formation of concentric lamellar bodies (CLB) were described in the caudate nucleus (CN) in schizophrenic brain ( Uranova and Orlovskaya, 1996). CLB were found surrounding dystrophic neurites in close apposition to synapses, to myelinated fibres and inside perivascular astroglial cell processes. We counted the number of CLB per unit tissue area in the head of CN and in the prefrontal cortex (PFC, area 10, layer VI) in three zones of
neuropil: in close apposition to synapses, to myelinated fibers and in perivascular end-feet of astrocytes in 19 normal controls and 20 schizophrenics (postmortem delay 4-6.5 hours). Significant increase in the number of CLB per 1000/~m2 was found in each of three zones of neuropil in schizophrenic group compared to controls (p<0.05). Postmortem interval, age, gender, neuroleptic exposure, duration of the disease did not account for the differences. Highly significant 9-fold increase in areal density of CLB was found in each of three zones of neuropil in the subgroup of familial schizophrenics (n=8, p<0.001) and in the subgroup of cases with predominantly negative symptoms compared to controls (n= 10, p<0.01 ). In the PFC areal density of CLB was also increased but not significantly compared to controls. The data suggest region specific membranous pathology in schizophrenic brain. Supported by the Theodore and Vada Stanley Foundation.
Reference l. Uranova N.A., Orlovskaya D.D. (1996) Ann. Psychiatr., 6, 55 72.
A. 182. O B S E R V E R - I N D E P E N D E N T , FULLY AUTOMATIZED IMAGE ANALYSIS OF CYTOARCHITECTURAL DISTURBANCES IN SCHIZOPHRENIA K. Vogeley*, H. H~tte, R. Tepest, P. Falkai
*Department of Psychiato', Sigmund-Freud-Str. 25, 53105 Bonn, FRG, Tel." 0044 228 287 6122; Fax: 0044 228 287 5025," E-mail: vogelev@uni-bonn, de The dysconnectivity hypothesis is one of the leading pathophysiological concepts. The empirical validation requires an examination of multiple brain sites in larger brain samples. Therefore, we further developed an observer-independent, fully automatized image analysis device based on the GLI method (Schleicher and Zilles, 1990). This fully automatized method allows the estimation of the density of neuronal perikarya in the cerebral cortex. Studies are performed in Brodmann area 10 in a postmortem brain sample of 19 schizophrenics and 19 controls. Per case 3 regions of interest in each hemisphere are selected, each covering a cortical surface of approximately 4ram. Microscopical images are scanned at high resolution (40 × objective) and digitized. 30 equidistant measurement fields are generated adjusting for differences in cortical thickness. Images are binarized according to a local threshold specific for the particular measurement fields. Neuronal density as the area covered by neuronal perikarya and particle counts are performed in each particular measurement field providing cytoarchitectonical profile curves. Preliminary results in 12 schizophrenia and 12 control cases revealed a significant decrease of mean neuronal density (MANOVA: F = 5.911, p = 0.02), whereas cortical thickness and particle count did not significantly differ between diagnostic groups. This method appears to be a useful scanning tool for the estimation of neuronal density. Supported by The Stanley Foundation.
A. 180. U L T R A S T R U C T U R A L ALTERATIONS OF GLUTAMATERGIC MOSSY FIBER SYNAPSES IN POSTMORTEM HIPPOCAMPUS OF SCHIZOPHRENICS N.S. Kolomeets, V.I. R a c h m a n o v a , D.D. Orlovskaya, N.A. U r a n o v a
Laboratory of Clinical Neuropathology, Mental Health Research Center, Zagor odnoe sh.2-2, Moscow, 113152, Russia The mossy fibers (MF), which are the axons of the granular cells of the dentate gyrus, use glutamate as a neurotransmitter, contain zinc, peptides and GABA. The MF have been associated with memory and special learning functions. It has been shown that the MF form giant terminals (MFT) to be in synaptic contacts mostly with branched dendritic spines of the pyramidal neurons in the CA3 region of the hippocampus. Qualitative and quantitative electron microscopic study of the MF synapses in the stratum lucidum of the CA3 region of the hippocampus was performed in 7 normal controls and 7 agematched chronic schizophrenics (postmortem delay 4-7 hours). Qualitative study showed a clumping of synaptic vesicles in part of MFT and a few dark degenerating MFT in schizophrenic brains compared to controls. Quantitative study demonstrated that 5 schizophrenic cases with predominantly positive symptoms differed significantly from controls by a reduction in total area and number of invaginated spines per MFT (p<0.01) and in the number of postsynaptic spines per MFT (p=0.012). No effects of postmortem delay, age, neuroleptic exposure were found. These preliminary data are consistent with the data about the reduction in regional zinc staining in postmortem hippocampus from schizophrenic patients (Goldsmith and Joyce, 1995) and suggest a hypofunction of MF synapses in some chronic schizophrenics. Supported by the Theodore and Vada Stanley Foundation.
R~/erences 1. S.K. Goldsmith, J.N. Joice (1995). Biol. Psychiatry 37, 2: 122 127.
A. 181. U L T R A S T R U C T U R A L MARKERS OF CELL MEMBRANE ABNORMALITIES IN POSTMORTEM SCHIZOPHRENIC BRAIN N.A. U r a n o v a , D.D. Orlovskaya, I.S. Zimina, O.V. Vikhreva, V.I. R a c h m a n o v a
Laboratory qf Clinical Neuropathology, Mental Health Research Center, Zagorodnoe sh.2-2, Moscow, 113152, Russ'ia Abnormalities of cell membranes with the formation of concentric lamellar bodies (CLB) were described in the caudate nucleus (CN) in schizophrenic brain ( Uranova and Orlovskaya, 1996). CLB were found surrounding dystrophic neurites in close apposition to synapses, to myelinated fibres and inside perivascular astroglial cell processes. We counted the number of CLB per unit tissue area in the head of CN and in the prefrontal cortex (PFC, area 10, layer VI) in three zones of
neuropil: in close apposition to synapses, to myelinated fibers and in perivascular end-feet of astrocytes in 19 normal controls and 20 schizophrenics (postmortem delay 4-6.5 hours). Significant increase in the number of CLB per 1000/~m2 was found in each of three zones of neuropil in schizophrenic group compared to controls (p<0.05). Postmortem interval, age, gender, neuroleptic exposure, duration of the disease did not account for the differences. Highly significant 9-fold increase in areal density of CLB was found in each of three zones of neuropil in the subgroup of familial schizophrenics (n=8, p<0.001) and in the subgroup of cases with predominantly negative symptoms compared to controls (n= 10, p<0.01 ). In the PFC areal density of CLB was also increased but not significantly compared to controls. The data suggest region specific membranous pathology in schizophrenic brain. Supported by the Theodore and Vada Stanley Foundation.
Reference l. Uranova N.A., Orlovskaya D.D. (1996) Ann. Psychiatr., 6, 55 72.
A. 182. O B S E R V E R - I N D E P E N D E N T , FULLY AUTOMATIZED IMAGE ANALYSIS OF CYTOARCHITECTURAL DISTURBANCES IN SCHIZOPHRENIA K. Vogeley*, H. H~tte, R. Tepest, P. Falkai
*Department of Psychiato', Sigmund-Freud-Str. 25, 53105 Bonn, FRG, Tel." 0044 228 287 6122; Fax: 0044 228 287 5025," E-mail: vogelev@uni-bonn, de The dysconnectivity hypothesis is one of the leading pathophysiological concepts. The empirical validation requires an examination of multiple brain sites in larger brain samples. Therefore, we further developed an observer-independent, fully automatized image analysis device based on the GLI method (Schleicher and Zilles, 1990). This fully automatized method allows the estimation of the density of neuronal perikarya in the cerebral cortex. Studies are performed in Brodmann area 10 in a postmortem brain sample of 19 schizophrenics and 19 controls. Per case 3 regions of interest in each hemisphere are selected, each covering a cortical surface of approximately 4ram. Microscopical images are scanned at high resolution (40 × objective) and digitized. 30 equidistant measurement fields are generated adjusting for differences in cortical thickness. Images are binarized according to a local threshold specific for the particular measurement fields. Neuronal density as the area covered by neuronal perikarya and particle counts are performed in each particular measurement field providing cytoarchitectonical profile curves. Preliminary results in 12 schizophrenia and 12 control cases revealed a significant decrease of mean neuronal density (MANOVA: F = 5.911, p = 0.02), whereas cortical thickness and particle count did not significantly differ between diagnostic groups. This method appears to be a useful scanning tool for the estimation of neuronal density. Supported by The Stanley Foundation.