Quantitative changes in perineuronal nets in development and posttraumatic condition

Lipachev, Nikita; Arnst, Nikita; Melnikova, Anastasiia; Jäälinoja, Harri; Kochneva, Anastasiya; Zhigalov, Alexander; Kulesskaya, Natalia; Аганов, А. В.; Мавликеев, М. О.; Rauvala, Heikki; Kiyasov, Andrey P.; Paveliev, Mikhail

doi:10.1007/s10735-019-09818-y

Cited by 21 publications

(21 citation statements)

References 54 publications

(81 reference statements)

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“…We note that the WFA-stained PNNs in adulthood (Fig 2E) were better formed and showed a more prominent structure as compared to those at P21 (Fig 1E). This is consistent with age-dependent maturation of the PNN structure that has been reported in many areas of the brain previously (Lipachev et al, 2019; Pizzorusso et al, 2002). Our results suggest that a transient elevation of serotonin in the postnatal temporal window alters the time-course of the appearance and maturation of PNNs around PV-positive neurons in a subfield-specific manner in the hippocampus.…”

Section: Resultssupporting

confidence: 93%

Postnatal fluoxetine treatment alters perineuronal net formation and maintenance in the hippocampus

Mukhopadhyay

Chatterjee

Tiwari

et al. 2020

Preprint

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Elevation of serotonin via postnatal fluoxetine (PNFlx) treatment during critical temporal windows is hypothesized to perturb the development of limbic circuits thus establishing a substratum for persistent disruption of mood-related behavior. We examined the impact of PNFlx treatment on the formation and maintenance of perineuronal nets (PNNs), extracellular matrix (ECM) structures that deposit primarily around inhibitory interneurons, and mark the closure of critical period plasticity. PNFlx treatment evoked a significant decline in PNN number, with a robust reduction in PNNs deposited around parvalbumin (PV) interneurons, within the CA1 and CA3 hippocampal subfields at postnatal day 21 in Sprague-Dawley rat pups. While the reduction in CA1 subfield PNN number was still observed in adulthood, we observed no change in colocalization of PV-positive interneurons with PNNs in the hippocampi of adult PNFlx animals. PNFlx treatment did not alter hippocampal parvalbumin, calretinin, or reelin-positive neuron numbers in PNFlx animals at P21 or in adulthood. We did observe a small, but significant increase in somatostatin (SST)-positive interneurons in the DG subfield of PNFlx-treated animals in adulthood. This was accompanied by altered GABA-A receptor subunit composition, increased dendritic complexity of apical dendrites of CA1 pyramidal neurons, and enhanced neuronal activation revealed by increased c-Fos-positive cell numbers within hippocampi of PNFlx-treated animals in adulthood. These results indicate that PNFlx treatment alters the developmental trajectory of PNNs within the hippocampus, raising the possibility of a disruption of critical period plasticity and the establishment of an altered excitation-inhibition balance within this key limbic brain region.

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Section: Resultssupporting

confidence: 93%

Postnatal fluoxetine treatment alters perineuronal net formation and maintenance in the hippocampus

Mukhopadhyay

Chatterjee

Tiwari

et al. 2020

Preprint

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“…Within a day after injury, CSPGs increase within and adjacent to the forming glial scar [15][16][17][18] . This upregulation also occurs in the PNN in areas rostral and caudal to the injury site in denervated distal targets [10][11][12][13][14]73 .…”

Section: Introductionmentioning

confidence: 99%

Recovery of forearm and fine digit function after chronic spinal cord injury by simultaneous blockade of inhibitory matrix CSPG production and the receptor PTPσ

Milton

Silver

Kwok

et al. 2022

Preprint

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Spinal cord injuries, for which there are limited effective clinical treatments, result in enduring paralysis and hypoesthesia due, in part, to the inhibitory microenvironment that develops and limits regeneration/sprouting, especially during chronic stages. Recently, we discovered that targeted enzymatic modulation of the potently inhibitory chondroitin sulfate proteoglycan (CSPG) component of the extracellular and perineuronal net (PNN) matrix via Chondroitinase ABC (ChABC) can rapidly restore robust respiratory function to the previously paralyzed hemi-diaphragm after remarkably long times post-injury (up to 1.5 years) following a cervical level 2 lateral hemi-transection. Importantly, ChABC treatment at cervical level 4 in this chronic model also elicited rapid, albeit modest, improvements in upper arm function. In the present study, we sought to further optimize and elucidate the capacity for nerve sprouting and/or regeneration to restore gross as well as fine motor control of the forearm and digits at lengthy chronic stages post injury. However, instead of using ChABC, we utilized a novel and more clinically relevant systemic, non-invasive combinatorial treatment strategy designed to both reduce (via oral delivery of 4-methylumbelliferone) and overcome inhibitory CSPGs (via sub-cutaneous delivery of the PTPσ CSPG receptor blocking peptide ISP) simultaneously and spatially extensively. Following a three-month upper cervical spinal hemi-lesion, we show that the combined treatment has a profound effect on functional recovery of the chronically paralyzed forelimb and paw, specifically during walking as well as precision movements of the digits. Our exciting pre-clinical findings will begin to dramatically enhance our understanding of the basic mechanisms underlying functionally beneficial regenerative events occurring at chronic injury stages for clinically relevant translational benefits.

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“…Holes in the net‐like structure of PNN are occupied by the synaptic boutons largely originating from other interneurons, but also from excitatory cells, suggesting the important role of PNNs in shaping the perisomatic innervation of PV+ cells (Arnst et al., 2016; Dityatev et al., 2007; Lipachev et al., 2019; Sigal, Bae, Bogart, Hensch, & Zhuang, 2019). A hole together with the surrounding perisynaptic ECM barrier can be viewed as a structural and functional PNN unit.…”

Section: Introductionmentioning

confidence: 99%

Fine structure analysis of perineuronal nets in the ketamine model of schizophrenia

Kaushik

Lipachev

Matuszko

et al. 2020

Eur J of Neuroscience

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Perineuronal nets (PNNs) represent a highly condensed specialized form of brain extracellular matrix (ECM) enwrapping mostly parvalbumin-positive interneurons in the brain in a mesh-like fashion. PNNs not only regulate the onset and completion of the critical period during postnatal brain development, control cell excitability, and synaptic transmission but are also implicated in several brain disorders including schizophrenia. Holes in the perineuronal nets, harboring the synaptic contacts, along with hole-surrounding ECM barrier can be viewed as PNN compartmentalization units that might determine the properties of synapses and heterosynaptic communication. In this study, we developed a novel open-source script for Fiji (ImageJ) to semi-automatically quantify structural alterations of PNNs such as the number of PNN units, area, mean intensity of PNN marker expression in 2D and 3D, shape parameters of PNN units in the ketamine-treated Sprague-Dawley rat model of schizophrenia using high-resolution confocal microscopic images. We discovered that the mean intensity of ECM within PNN units is inversely correlated with the area and the perimeter of the PNN holes. The intensity, size, and shape of PNN units proved to be three major principal factors to describe their variability. Ketamine-treated ratsThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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Quantitative changes in perineuronal nets in development and posttraumatic condition

Cited by 21 publications

References 54 publications

Postnatal fluoxetine treatment alters perineuronal net formation and maintenance in the hippocampus

Postnatal fluoxetine treatment alters perineuronal net formation and maintenance in the hippocampus

Recovery of forearm and fine digit function after chronic spinal cord injury by simultaneous blockade of inhibitory matrix CSPG production and the receptor PTPσ

Fine structure analysis of perineuronal nets in the ketamine model of schizophrenia

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