The Experts below are selected from a list of 110277 Experts worldwide ranked by ideXlab platform
David A. Lewis - One of the best experts on this subject based on the ideXlab platform.
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Density of small dendritic spines and microtubule-associated-protein-2 immunoreactivity in the primary auditory cortex of subjects with schizophrenia
Neuropsychopharmacology, 2019Co-Authors: Brandon C. Mckinney, Allan R. Sampson, David A. Lewis, Matthew L. Macdonald, Jason T. Newman, Micah A. Shelton, Rebecca A. Degiosio, Ryan M. Kelly, Kenneth N. Fish, Robert A. SweetAbstract:Previously, we demonstrated that dendritic spine density (DSD) in Deep Layer 3 of the primary auditory cortex (A1) is lower, due to having fewer small spines, in subjects with schizophrenia (SZ) than non-psychiatric control (NPC) subjects. We also previously demonstrated that microtubule-associated-protein-2 immunoreactivity (MAP2-IR) in A1 Deep Layer 3 is lower, and positively correlated with DSD, in SZ subjects. Here, we first sought to confirm these findings in an independent cohort of 25 SZ-NPC subject pairs (cohort 1). We used immunohistochemistry and confocal microscopy to measure DSD and MAP2-IR in A1 Deep Layer 3. Consistent with previous studies, both DSD and MAP2-IR were lower in SZ subjects. We then tested the hypothesis that MAP2-IR mediates the effect of SZ on DSD in a cohort of 45 SZ-NPC subject pairs (combined cohort) that included all subjects from cohort 1 and two previously studied cohorts. Based on the distribution of MAP2-IR values in NPC subjects, we categorized each SZ subject as having either low MAP2-IR (SZ MAP2-IR(low)) or normal MAP2-IR (SZ MAP2-IR(normal)). Among SZ MAP-IR(low) subjects, mean DSD was significantly lower than in NPC subjects. However, mean DSD did not differ between SZ MAP2-IR(normal) and NPC subjects. Moreover, MAP2-IR statistically mediated small spine differences, with lower MAP2-IR values associated with fewer small spines. Our findings confirm that low density of small spines and low MAP2-IR are robust SZ phenotypes and suggest that MAP2-IR mediates the effect of SZ on DSD.
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Somal size of prefrontal cortical pyramidal neurons in schizophrenia: differential effects across neuronal subpopulations.
Biological psychiatry, 2003Co-Authors: Joseph N. Pierri, Christine L. E. Volk, Sungyoung Auh, Allan R. Sampson, David A. LewisAbstract:Abstract Background Cognitive dysfunction in schizophrenia may be related to morphologic abnormalities of pyramidal neurons in the dorsal prefrontal cortex (dPFC) and the largest pyramidal neurons in Deep Layer 3 may be most affected. Immunoreactivity (IR) for the nonphosphorylated epitopes of neurofilament protein (NNFP) identifies a subset of large dPFC Deep Layer 3 pyramidal neurons. We tested the hypotheses that the average size of NNFP-IR neurons is smaller in schizophrenia and that the decrease in size of these neurons is greater than that observed in the general population of Deep Layer 3 pyramidal neurons. Methods We estimated the mean somal volume of NNFP-IR neurons in Deep Layer 3 of 9 in 13 matched pairs of control and schizophrenia subjects and compared the differences in somal size of NNFP-IR neurons to the differences in size of all Deep Layer 3 pyramidal neurons identified in Nissl-stained material. Results In subjects with schizophrenia, the somal volume of NNFP-IR neurons was nonsignificantly decreased by 6.6%, whereas that of the Nissl-stained pyramidal neurons was significantly decreased by 14.2%. Conclusions These results suggest that the NNFP-IR subpopulation of dPFC pyramidal neurons are not preferentially affected in schizophrenia. Thus, a subpopulation of dPFC Deep Layer 3 pyramidal neurons, other than those identified by NNFP-IR, may be selectively vulnerable in schizophrenia.
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Decreased Somal Size of Deep Layer 3 Pyramidal Neurons in the Prefrontal Cortex of Subjects With Schizophrenia
Archives of general psychiatry, 2001Co-Authors: Joseph N. Pierri, Christine L. E. Volk, Sungyoung Auh, Allan R. Sampson, David A. LewisAbstract:Background Schizophrenia is associated with deficits in working memory, a cognitive function that depends on the connections of the prefrontal cortex (PFC) with the thalamus and other cortical regions. Pyramidal neurons in PFC Deep Layer 3 play a central role in both thalamocortical and corticocortical circuitry. Given that somal size tends to be associated with both the dendritic and axonal architecture of a neuron, abnormalities in these circuits in schizophrenia may be associated with a change in the somal size of Deep Layer 3 pyramidal neurons. Methods We used design-based stereology to estimate the somal volume of pyramidal neurons in Deep Layer 3 of PFC area 9 in 28 subjects with schizophrenia, each of whom was matched to 1 normal comparison subject for sex, age, and postmortem interval. Results The geometric mean of the somal volume estimates in the subjects with schizophrenia was significantly ( P =.02) decreased by 9.2%. This decrease was associated with a shift in the distribution of somal volumes toward smaller sizes. Neither antipsychotic medication treatment history nor duration of illness was associated with somal size. Conclusions These findings independently replicate previous reports of decreased somal size in the PFC in schizophrenia. The reduction in size of Deep Layer 3 pyramidal neurons is consistent with abnormalities in thalamocortical and corticocortical circuitry, suggesting that disruption of these circuits may contribute to cognitive abnormalities in schizophrenia.
Florina Moldovan - One of the best experts on this subject based on the ideXlab platform.
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collagenase 3 matrix metalloprotease 13 is preferentially localized in the Deep Layer of human arthritic cartilage in situ in vitro mimicking effect by transforming growth factor β
Arthritis & Rheumatism, 1997Co-Authors: Florina Moldovan, Jeanpierre Pelletier, John E Hambor, J M Cloutier, Johanne MartelpelletierAbstract:OBJECTIVE To examine, by immunohistochemistry, the localization and distribution of human collagenase-3 in normal, osteoarthritis (OA), and rheumatoid arthritis (RA) cartilage, and to investigate the effects of interleukin-1beta (IL-1beta) and transforming growth factor beta (TGFbeta) on the synthesis and distribution of collagenase-3. METHODS Human cartilage specimens were obtained from tibial plateaus. In the first series of experiments, the OA specimens were excised from fibrillated and nonfibrillated areas of cartilage, and RA specimens were excised from lesional areas, including the cartilage-pannus junction when present. In the second series, full strips of cartilage were processed for culture in the presence or absence of IL-1beta (100 units/ml) or TGFbeta (150 ng/ml). Each specimen was processed for immunohistochemical analysis using a collagenase-3 monoclonal antibody. RESULTS The number of cells that stained for collagenase-3 in normal cartilage was very low (approximately 3%). In OA cartilage, the percentage increased dramatically, and no difference was found between fibrillated and nonfibrillated areas. A statistically significant increase in the percentage of cells staining for collagenase-3 was found in the Deep Layer compared with the superficial Layer. This finding was noted in both the fibrillated areas (mean +/- SEM 58.4 +/- 1.6% and 40.1 +/- 3.9%, respectively; P < 0.007) and the nonfibrillated areas (55.4 +/- 3.2% and 43.2 +/- 2.7%; P < 0.01). Similarly, RA cartilage showed a statistically significant (P < 0.001) increase in the level of chondrocytes staining positive for collagenase-3 in the Deep Layers (46.4 +/- 4.1%) compared with the superficial Layers (26.2 +/- 3.4%). In these RA specimens, the numbers of positively staining chondrocytes were similar both close to and at a distance from the pannus junction. Both IL-1beta and TGFbeta increased the number of chondrocytes producing collagenase-3. Interestingly, in normal specimens, TGFbeta had a predominant effect in the Deep Layers, while IL-1beta had a greater effect on the superficial Layers. CONCLUSION This study demonstrates that, in situ, the increase in the level of chondrocytes synthesizing collagenase-3 in arthritic cartilage is predominant in the Deep Layers. The results further indicate that TGFbeta can up-regulate the level of this enzyme and, in normal cartilage in vitro, can cause a mimicking of the in situ distribution observed in arthritic cartilage.
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Collagenase‐3 (matrix metalloprotease 13) is preferentially localized in the Deep Layer of human arthritic cartilage in situ. In vitro mimicking effect by transforming growth factor β
Arthritis and rheumatism, 1997Co-Authors: Florina Moldovan, Jeanpierre Pelletier, John E Hambor, Johanne Martel-pelletierAbstract:OBJECTIVE To examine, by immunohistochemistry, the localization and distribution of human collagenase-3 in normal, osteoarthritis (OA), and rheumatoid arthritis (RA) cartilage, and to investigate the effects of interleukin-1beta (IL-1beta) and transforming growth factor beta (TGFbeta) on the synthesis and distribution of collagenase-3. METHODS Human cartilage specimens were obtained from tibial plateaus. In the first series of experiments, the OA specimens were excised from fibrillated and nonfibrillated areas of cartilage, and RA specimens were excised from lesional areas, including the cartilage-pannus junction when present. In the second series, full strips of cartilage were processed for culture in the presence or absence of IL-1beta (100 units/ml) or TGFbeta (150 ng/ml). Each specimen was processed for immunohistochemical analysis using a collagenase-3 monoclonal antibody. RESULTS The number of cells that stained for collagenase-3 in normal cartilage was very low (approximately 3%). In OA cartilage, the percentage increased dramatically, and no difference was found between fibrillated and nonfibrillated areas. A statistically significant increase in the percentage of cells staining for collagenase-3 was found in the Deep Layer compared with the superficial Layer. This finding was noted in both the fibrillated areas (mean +/- SEM 58.4 +/- 1.6% and 40.1 +/- 3.9%, respectively; P < 0.007) and the nonfibrillated areas (55.4 +/- 3.2% and 43.2 +/- 2.7%; P < 0.01). Similarly, RA cartilage showed a statistically significant (P < 0.001) increase in the level of chondrocytes staining positive for collagenase-3 in the Deep Layers (46.4 +/- 4.1%) compared with the superficial Layers (26.2 +/- 3.4%). In these RA specimens, the numbers of positively staining chondrocytes were similar both close to and at a distance from the pannus junction. Both IL-1beta and TGFbeta increased the number of chondrocytes producing collagenase-3. Interestingly, in normal specimens, TGFbeta had a predominant effect in the Deep Layers, while IL-1beta had a greater effect on the superficial Layers. CONCLUSION This study demonstrates that, in situ, the increase in the level of chondrocytes synthesizing collagenase-3 in arthritic cartilage is predominant in the Deep Layers. The results further indicate that TGFbeta can up-regulate the level of this enzyme and, in normal cartilage in vitro, can cause a mimicking of the in situ distribution observed in arthritic cartilage.
Allan R. Sampson - One of the best experts on this subject based on the ideXlab platform.
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Density of small dendritic spines and microtubule-associated-protein-2 immunoreactivity in the primary auditory cortex of subjects with schizophrenia
Neuropsychopharmacology, 2019Co-Authors: Brandon C. Mckinney, Allan R. Sampson, David A. Lewis, Matthew L. Macdonald, Jason T. Newman, Micah A. Shelton, Rebecca A. Degiosio, Ryan M. Kelly, Kenneth N. Fish, Robert A. SweetAbstract:Previously, we demonstrated that dendritic spine density (DSD) in Deep Layer 3 of the primary auditory cortex (A1) is lower, due to having fewer small spines, in subjects with schizophrenia (SZ) than non-psychiatric control (NPC) subjects. We also previously demonstrated that microtubule-associated-protein-2 immunoreactivity (MAP2-IR) in A1 Deep Layer 3 is lower, and positively correlated with DSD, in SZ subjects. Here, we first sought to confirm these findings in an independent cohort of 25 SZ-NPC subject pairs (cohort 1). We used immunohistochemistry and confocal microscopy to measure DSD and MAP2-IR in A1 Deep Layer 3. Consistent with previous studies, both DSD and MAP2-IR were lower in SZ subjects. We then tested the hypothesis that MAP2-IR mediates the effect of SZ on DSD in a cohort of 45 SZ-NPC subject pairs (combined cohort) that included all subjects from cohort 1 and two previously studied cohorts. Based on the distribution of MAP2-IR values in NPC subjects, we categorized each SZ subject as having either low MAP2-IR (SZ MAP2-IR(low)) or normal MAP2-IR (SZ MAP2-IR(normal)). Among SZ MAP-IR(low) subjects, mean DSD was significantly lower than in NPC subjects. However, mean DSD did not differ between SZ MAP2-IR(normal) and NPC subjects. Moreover, MAP2-IR statistically mediated small spine differences, with lower MAP2-IR values associated with fewer small spines. Our findings confirm that low density of small spines and low MAP2-IR are robust SZ phenotypes and suggest that MAP2-IR mediates the effect of SZ on DSD.
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Somal size of prefrontal cortical pyramidal neurons in schizophrenia: differential effects across neuronal subpopulations.
Biological psychiatry, 2003Co-Authors: Joseph N. Pierri, Christine L. E. Volk, Sungyoung Auh, Allan R. Sampson, David A. LewisAbstract:Abstract Background Cognitive dysfunction in schizophrenia may be related to morphologic abnormalities of pyramidal neurons in the dorsal prefrontal cortex (dPFC) and the largest pyramidal neurons in Deep Layer 3 may be most affected. Immunoreactivity (IR) for the nonphosphorylated epitopes of neurofilament protein (NNFP) identifies a subset of large dPFC Deep Layer 3 pyramidal neurons. We tested the hypotheses that the average size of NNFP-IR neurons is smaller in schizophrenia and that the decrease in size of these neurons is greater than that observed in the general population of Deep Layer 3 pyramidal neurons. Methods We estimated the mean somal volume of NNFP-IR neurons in Deep Layer 3 of 9 in 13 matched pairs of control and schizophrenia subjects and compared the differences in somal size of NNFP-IR neurons to the differences in size of all Deep Layer 3 pyramidal neurons identified in Nissl-stained material. Results In subjects with schizophrenia, the somal volume of NNFP-IR neurons was nonsignificantly decreased by 6.6%, whereas that of the Nissl-stained pyramidal neurons was significantly decreased by 14.2%. Conclusions These results suggest that the NNFP-IR subpopulation of dPFC pyramidal neurons are not preferentially affected in schizophrenia. Thus, a subpopulation of dPFC Deep Layer 3 pyramidal neurons, other than those identified by NNFP-IR, may be selectively vulnerable in schizophrenia.
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Decreased Somal Size of Deep Layer 3 Pyramidal Neurons in the Prefrontal Cortex of Subjects With Schizophrenia
Archives of general psychiatry, 2001Co-Authors: Joseph N. Pierri, Christine L. E. Volk, Sungyoung Auh, Allan R. Sampson, David A. LewisAbstract:Background Schizophrenia is associated with deficits in working memory, a cognitive function that depends on the connections of the prefrontal cortex (PFC) with the thalamus and other cortical regions. Pyramidal neurons in PFC Deep Layer 3 play a central role in both thalamocortical and corticocortical circuitry. Given that somal size tends to be associated with both the dendritic and axonal architecture of a neuron, abnormalities in these circuits in schizophrenia may be associated with a change in the somal size of Deep Layer 3 pyramidal neurons. Methods We used design-based stereology to estimate the somal volume of pyramidal neurons in Deep Layer 3 of PFC area 9 in 28 subjects with schizophrenia, each of whom was matched to 1 normal comparison subject for sex, age, and postmortem interval. Results The geometric mean of the somal volume estimates in the subjects with schizophrenia was significantly ( P =.02) decreased by 9.2%. This decrease was associated with a shift in the distribution of somal volumes toward smaller sizes. Neither antipsychotic medication treatment history nor duration of illness was associated with somal size. Conclusions These findings independently replicate previous reports of decreased somal size in the PFC in schizophrenia. The reduction in size of Deep Layer 3 pyramidal neurons is consistent with abnormalities in thalamocortical and corticocortical circuitry, suggesting that disruption of these circuits may contribute to cognitive abnormalities in schizophrenia.
Joseph N. Pierri - One of the best experts on this subject based on the ideXlab platform.
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Somal size of prefrontal cortical pyramidal neurons in schizophrenia: differential effects across neuronal subpopulations.
Biological psychiatry, 2003Co-Authors: Joseph N. Pierri, Christine L. E. Volk, Sungyoung Auh, Allan R. Sampson, David A. LewisAbstract:Abstract Background Cognitive dysfunction in schizophrenia may be related to morphologic abnormalities of pyramidal neurons in the dorsal prefrontal cortex (dPFC) and the largest pyramidal neurons in Deep Layer 3 may be most affected. Immunoreactivity (IR) for the nonphosphorylated epitopes of neurofilament protein (NNFP) identifies a subset of large dPFC Deep Layer 3 pyramidal neurons. We tested the hypotheses that the average size of NNFP-IR neurons is smaller in schizophrenia and that the decrease in size of these neurons is greater than that observed in the general population of Deep Layer 3 pyramidal neurons. Methods We estimated the mean somal volume of NNFP-IR neurons in Deep Layer 3 of 9 in 13 matched pairs of control and schizophrenia subjects and compared the differences in somal size of NNFP-IR neurons to the differences in size of all Deep Layer 3 pyramidal neurons identified in Nissl-stained material. Results In subjects with schizophrenia, the somal volume of NNFP-IR neurons was nonsignificantly decreased by 6.6%, whereas that of the Nissl-stained pyramidal neurons was significantly decreased by 14.2%. Conclusions These results suggest that the NNFP-IR subpopulation of dPFC pyramidal neurons are not preferentially affected in schizophrenia. Thus, a subpopulation of dPFC Deep Layer 3 pyramidal neurons, other than those identified by NNFP-IR, may be selectively vulnerable in schizophrenia.
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Decreased Somal Size of Deep Layer 3 Pyramidal Neurons in the Prefrontal Cortex of Subjects With Schizophrenia
Archives of general psychiatry, 2001Co-Authors: Joseph N. Pierri, Christine L. E. Volk, Sungyoung Auh, Allan R. Sampson, David A. LewisAbstract:Background Schizophrenia is associated with deficits in working memory, a cognitive function that depends on the connections of the prefrontal cortex (PFC) with the thalamus and other cortical regions. Pyramidal neurons in PFC Deep Layer 3 play a central role in both thalamocortical and corticocortical circuitry. Given that somal size tends to be associated with both the dendritic and axonal architecture of a neuron, abnormalities in these circuits in schizophrenia may be associated with a change in the somal size of Deep Layer 3 pyramidal neurons. Methods We used design-based stereology to estimate the somal volume of pyramidal neurons in Deep Layer 3 of PFC area 9 in 28 subjects with schizophrenia, each of whom was matched to 1 normal comparison subject for sex, age, and postmortem interval. Results The geometric mean of the somal volume estimates in the subjects with schizophrenia was significantly ( P =.02) decreased by 9.2%. This decrease was associated with a shift in the distribution of somal volumes toward smaller sizes. Neither antipsychotic medication treatment history nor duration of illness was associated with somal size. Conclusions These findings independently replicate previous reports of decreased somal size in the PFC in schizophrenia. The reduction in size of Deep Layer 3 pyramidal neurons is consistent with abnormalities in thalamocortical and corticocortical circuitry, suggesting that disruption of these circuits may contribute to cognitive abnormalities in schizophrenia.
Johanne Martelpelletier - One of the best experts on this subject based on the ideXlab platform.
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collagenase 3 matrix metalloprotease 13 is preferentially localized in the Deep Layer of human arthritic cartilage in situ in vitro mimicking effect by transforming growth factor β
Arthritis & Rheumatism, 1997Co-Authors: Florina Moldovan, Jeanpierre Pelletier, John E Hambor, J M Cloutier, Johanne MartelpelletierAbstract:OBJECTIVE To examine, by immunohistochemistry, the localization and distribution of human collagenase-3 in normal, osteoarthritis (OA), and rheumatoid arthritis (RA) cartilage, and to investigate the effects of interleukin-1beta (IL-1beta) and transforming growth factor beta (TGFbeta) on the synthesis and distribution of collagenase-3. METHODS Human cartilage specimens were obtained from tibial plateaus. In the first series of experiments, the OA specimens were excised from fibrillated and nonfibrillated areas of cartilage, and RA specimens were excised from lesional areas, including the cartilage-pannus junction when present. In the second series, full strips of cartilage were processed for culture in the presence or absence of IL-1beta (100 units/ml) or TGFbeta (150 ng/ml). Each specimen was processed for immunohistochemical analysis using a collagenase-3 monoclonal antibody. RESULTS The number of cells that stained for collagenase-3 in normal cartilage was very low (approximately 3%). In OA cartilage, the percentage increased dramatically, and no difference was found between fibrillated and nonfibrillated areas. A statistically significant increase in the percentage of cells staining for collagenase-3 was found in the Deep Layer compared with the superficial Layer. This finding was noted in both the fibrillated areas (mean +/- SEM 58.4 +/- 1.6% and 40.1 +/- 3.9%, respectively; P < 0.007) and the nonfibrillated areas (55.4 +/- 3.2% and 43.2 +/- 2.7%; P < 0.01). Similarly, RA cartilage showed a statistically significant (P < 0.001) increase in the level of chondrocytes staining positive for collagenase-3 in the Deep Layers (46.4 +/- 4.1%) compared with the superficial Layers (26.2 +/- 3.4%). In these RA specimens, the numbers of positively staining chondrocytes were similar both close to and at a distance from the pannus junction. Both IL-1beta and TGFbeta increased the number of chondrocytes producing collagenase-3. Interestingly, in normal specimens, TGFbeta had a predominant effect in the Deep Layers, while IL-1beta had a greater effect on the superficial Layers. CONCLUSION This study demonstrates that, in situ, the increase in the level of chondrocytes synthesizing collagenase-3 in arthritic cartilage is predominant in the Deep Layers. The results further indicate that TGFbeta can up-regulate the level of this enzyme and, in normal cartilage in vitro, can cause a mimicking of the in situ distribution observed in arthritic cartilage.
