Developmental Pattern of Perineuronal Nets in the Human Prefrontal Cortex and Their Deficit in Schizophrenia

Mauney, Sarah A.; Athanas, Katina M.; Pantazopoulos, Harry; Shaskan, Noel; Passeri, Eleonora; Berretta, Sabina; Woo, Tsung-Ung W.

doi:10.1016/j.biopsych.2013.05.007

Cited by 253 publications

(296 citation statements)

References 61 publications

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“…In the comparison subjects, qualitative analyses revealed that PV neurons and PNNs (identified by WFA labeling or aggrecan immunoreactivity) were present in greatest density in layer 3 of DLPFC area 9 (Figure 1a-1), consistent with prior findings (Hashimoto et al, 2003;Mauney et al, 2013). Many PV neurons were surrounded by PNNs and the majority of PNNs surrounded PV neurons; however, some …”

Section: Pv and Pnn Labeling Is Prominent In Dlpfc Layersupporting

confidence: 85%

“…3b), indicating that cells with normal levels of PV protein are readily detectable. Thus, prior reports of apparently lower PV cell density (Beasley et al, 2002) are likely due to lower levels of PV protein and reported losses of PNNs (Mauney et al, 2013) are not likely due to loss of PV neurons.…”

Section: Discussion Pv Cells and Pnns Are Normal In Density But More mentioning

confidence: 78%

“…Because these data suggest that reports of lower PNN density in the DLPFC of schizophrenia subjects (Mauney et al, 2013) is not due to a loss of PV cells, we investigated whether the proportion of PV cells with PNNs was altered in schizophrenia. At low magnification, the mean percentage of PV-positive cells with WFA-positive PNNs in schizophrenia subjects (53.5 ± 24.7%) was lower (F 1,27 = 6.1, P = 0.02) compared with that in comparison subjects (64.6 ± 20.4%), although this did not achieve statistical significance in the unpaired ANCOVA (Supplementary Table 2).…”

Section: Labeling Intensity But Not Density Of Pnns Is Lower In Schmentioning

confidence: 99%

“…Several PNN proteoglycans, the lecticans, are highly glycosylated, and one, aggrecan, is highly enriched in mature PNNs (Bitanihirwe and Woo, 2014). The density of PNNs labeled with Wisteria floribunda agglutinin (WFA), a lectin that binds to specific carbohydrate moieties on proteoglycans, has been reported to be markedly lower in the entorhinal and prefrontal cortices in schizophrenia (Mauney et al, 2013;Pantazopoulos et al, 2010Pantazopoulos et al, , 2015.…”

Section: Introductionmentioning

confidence: 99%

“…PNNs were labeled with WFA and an antibody that recognizes aggrecan, in combination with markers of PV neurons and PCs, in DLPFC layer 3 from schizophrenia and healthy comparison subjects as layer 3 has the highest density of both PV neurons (Hashimoto et al, 2003) and PNNs (Mauney et al, 2013). The density of PV-positive cells and the intensity of PV labeling per neuron were quantified along with the proportion of PV cells surrounded by PNNs.…”

Section: Introductionmentioning

confidence: 99%

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Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

Enwright

Sanapala

Foglio

et al. 2016

Neuropsychopharmacol

193

139

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Alterations in cortical parvalbumin (PV)-containing neurons, including a reduced density of detectable neurons and lower PV levels, have frequently been reported in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia subjects. Most PV neurons are surrounded by perineuronal nets (PNNs) and the density of PNNs, as detected by Wisteria floribunda agglutinin (WFA) labeling, has been reported to be lower in schizophrenia. However, the nature of these PNN alterations, and their relationship to disease-related changes in PV neurons, has not been assessed. Using confocal microscopy, we quantified the densities and fluorescence intensities of PV neurons and PNNs labeled with WFA or immunoreactive for the major PNN protein, aggrecan, in the DLPFC from schizophrenia and matched comparison subjects. In schizophrenia, the densities of PV cells and of PNNs were not altered; however, the fluorescence intensities of PV immunoreactivity in cell bodies and of WFA labeling and aggrecan immunoreactivity in individual PNNs around PV cells were lower. These findings indicate that the normal complements of PV cells and PNNs are preserved in schizophrenia, but the levels of PV protein and of individual PNN components, especially the carbohydrate moieties on proteoglycans to which WFA binds, are lower. Given the roles of PV neurons in regulating DLPFC microcircuits and of PNNs in regulating PV cellular physiology, the identified alterations in PV neurons and their PNNs could contribute to DLPFC dysfunction in schizophrenia.

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Section: Pv and Pnn Labeling Is Prominent In Dlpfc Layersupporting

confidence: 85%

Section: Discussion Pv Cells and Pnns Are Normal In Density But More mentioning

confidence: 78%

Section: Labeling Intensity But Not Density Of Pnns Is Lower In Schmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

Enwright

Sanapala

Foglio

et al. 2016

Neuropsychopharmacol

193

139

View full text Add to dashboard Cite

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Decoding perineuronal net glycan sulfation patterns in the Alzheimer's disease brain

Logsdon

Francis

Richardson

et al. 2021

Alzheimer's & Dementia

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The extracellular matrix (ECM) of the brain comprises unique glycan "sulfation codes" that influence neurological function. Perineuronal nets (PNNs) are chondroitin sulfate-glycosaminoglycan (CS-GAG) containing matrices that enmesh neural networks involved in memory and cognition, and loss of PNN matrices is reported in patients with neurocognitive and neuropsychiatric disorders including Alzheimer's disease (AD). Using liquid chromatography tandem mass spectrometry (LC-MS/MS), we show that patients with a clinical diagnosis of AD-related dementia undergo a recoding of their PNN-associated CS-GAGs that correlates to Braak stage progression, hyperphosphorylated tau (p-tau) accumulation, and cognitive impairment. As these CS-GAG sulfation changes are detectable prior to the regional onset of classical AD pathology, they may contribute to the initiation and/or progression of the underlying degenerative processes and implicate the brain matrix sulfation code as a key player in the development of AD clinicopathology.

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Extracellular matrix protein expression is brain region dependent

Dauth

Grevesse

Pantazopoulos

et al. 2016

J of Comparative Neurology

Self Cite

111

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In the brain, extracellular matrix (ECM) components form networks that contribute to structural and functional diversity. Maladaptive remodeling of ECM networks has been reported in neurodegenerative and psychiatric disorders, suggesting that the brain microenvironment is a dynamic structure. A lack of quantitative information about ECM distribution in the brain hinders an understanding of region-specific ECM functions and the role of ECM in health and disease. We hypothesized that each ECM protein as well as specific ECM structures, such as perineuronal nets (PNNs) and interstitial matrix, are differentially distributed throughout the brain, contributing to the unique structure and function in the various regions of the brain. To test our hypothesis, we quantitatively analyzed the distribution, colocalization, and protein expression of aggrecan, brevican, and tenascin-R throughout the rat brain utilizing immunohistochemistry and mass spectrometry analysis and assessed the effect of aggrecan, brevican, and/or tenascin-R on neurite outgrowth in vitro. We focused on aggrecan, brevican, and tenascin-R as they are especially expressed in the mature brain, and have established roles in brain development, plasticity, and neurite outgrowth. The results revealed a differentiated distribution of all three proteins throughout the brain and indicated that their presence significantly reduces neurite outgrowth in a 3D in vitro environment. These results underline the importance of a unique and complex ECM distribution for brain physiology and suggest that encoding the distribution of distinct ECM proteins throughout the brain will aid in understanding their function in physiology and in turn assist in identifying their role in disease. J. Comp. Neurol. 524:1309-1336, 2016. © 2016 Wiley Periodicals, Inc.

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Developmental Pattern of Perineuronal Nets in the Human Prefrontal Cortex and Their Deficit in Schizophrenia

Cited by 253 publications

References 61 publications

Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

Decoding perineuronal net glycan sulfation patterns in the Alzheimer's disease brain

Extracellular matrix protein expression is brain region dependent

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