scholarly journals Perineuronal Net Dynamics in the Pathophysiology of Epilepsy

2021 ◽  
pp. 153575972110186
Author(s):  
Lata Chaunsali ◽  
Bhanu P. Tewari ◽  
Harald Sontheimer
Keyword(s):  
Critical Period ◽  
Seizure Activity ◽  
Perineuronal Nets ◽  
Rodent Models ◽  
Central Nervous System Diseases ◽  
Intrinsic Properties ◽  
Perineuronal Net ◽  
Ecm Remodeling ◽  
Activity Inhibition ◽  
Wide Range

Perineuronal nets (PNNs) are condensed extracellular matrix (ECM) assemblies of polyanionic chondroitin sulfate proteoglycans, hyaluronan, and tenascins that primarily wrap around GABAergic parvalbumin (PV) interneurons. During development, PNN formation terminates the critical period of neuroplasticity, a process that can be reversed by experimental disruption of PNNs. Perineuronal nets also regulate the intrinsic properties of the enclosed PV neurons thereby maintaining their inhibitory activity. Recent studies have implicated PNNs in central nervous system diseases as well as PV neuron dysfunction; consequently, they have further been associated with altered inhibition, particularly in the genesis of epilepsy. A wide range of seizure presentations in human and rodent models exhibit ECM remodeling with PNN disruption due to elevated protease activity. Inhibition of PNN proteolysis reduces seizure activity suggesting that PNN degrading enzymes may be potential novel therapeutic targets.

scholarly journals An Extracellular Perspective on CNS Maturation: Perineuronal Nets and the Control of Plasticity

2021 ◽  
Vol 22 (5) ◽  
pp. 2434
Author(s):  
Daniela Carulli ◽  
Joost Verhaagen
Keyword(s):  
Critical Period ◽  
Brain Plasticity ◽  
Time Windows ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Postnatal Life ◽  
Perineuronal Nets ◽  
Critical Periods ◽  
Perineuronal Net ◽  
Memory Processes

During restricted time windows of postnatal life, called critical periods, neural circuits are highly plastic and are shaped by environmental stimuli. In several mammalian brain areas, from the cerebral cortex to the hippocampus and amygdala, the closure of the critical period is dependent on the formation of perineuronal nets. Perineuronal nets are a condensed form of an extracellular matrix, which surrounds the soma and proximal dendrites of subsets of neurons, enwrapping synaptic terminals. Experimentally disrupting perineuronal nets in adult animals induces the reactivation of critical period plasticity, pointing to a role of the perineuronal net as a molecular brake on plasticity as the critical period closes. Interestingly, in the adult brain, the expression of perineuronal nets is remarkably dynamic, changing its plasticity-associated conditions, including memory processes. In this review, we aimed to address how perineuronal nets contribute to the maturation of brain circuits and the regulation of adult brain plasticity and memory processes in physiological and pathological conditions.

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

2020 ◽  
Author(s):  
Sourish Mukhopadhyay ◽  
Ashmita Chatterjee ◽  
Praachi Tiwari ◽  
Utkarsha Ghai ◽  
Vidita A. Vaidya
Keyword(s):  
Extracellular Matrix ◽  
Critical Period ◽  
Developmental Trajectory ◽  
Postnatal Life ◽  
Perineuronal Nets ◽  
Receptor Subunit ◽  
Neuronal Activation ◽  
Perineuronal Net ◽  
Hippocampal Subfields ◽  
The Impact

AbstractElevation 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.Significance StatementClinical and preclinical studies indicate that developmental exposure to fluoxetine programs persistent dysregulation of mood-related behaviors. This is hypothesized to involve the disruption of the normal development of key brain regions, such as the hippocampus that regulate mood behaviors. We show that postnatal exposure to fluoxetine alters hippocampal perineuronal nets (PNNs), extracellular matrix structures that regulate plasticity and mark the closure of critical periods. The decline in PNNs is noted in early postnatal life, and persists into adulthood in specific hippocampal subfields. Adult animals with a history of postnatal fluoxetine exposure exhibit altered numbers of somatostatin interneurons, GABA receptor subunit expression and neuronal activation within the hippocampus. This indicates that postnatal fluoxetine disrupts the normal developmental trajectory of the hippocampus.

scholarly journals In Vitro Cellular Uptake Studies of Self-Assembled Fluorinated Nanoparticles Labelled with Antibodies

Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1906
Author(s):  
Mona Atabakhshi-Kashi ◽  
Mónica Carril ◽  
Hossein Mahdavi ◽  
Wolfgang J. Parak ◽  
Carolina Carrillo-Carrion ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cellular Uptake ◽  
Hydrophobic Interactions ◽  
Intrinsic Properties ◽  
Wide Range ◽  
Self Assembled ◽  
Uptake Studies ◽  
Targeting Ability ◽  
Fluorinated Nanoparticles

Nanoparticles (NPs) functionalized with antibodies (Abs) on their surface are used in a wide range of bioapplications. Whereas the attachment of antibodies to single NPs to trigger the internalization in cells via receptor-mediated endocytosis has been widely studied, the conjugation of antibodies to larger NP assemblies has been much less explored. Taking into account that NP assemblies may be advantageous for some specific applications, the possibility of incorporating targeting ligands is quite important. Herein, we performed the effective conjugation of antibodies onto a fluorescent NP assembly, which consisted of fluorinated Quantum Dots (QD) self-assembled through fluorine–fluorine hydrophobic interactions. Cellular uptake studies by confocal microscopy and flow cytometry revealed that the NP assembly underwent the same uptake procedure as individual NPs; that is, the antibodies retained their targeting ability once attached to the nanoassembly, and the NP assembly preserved its intrinsic properties (i.e., fluorescence in the case of QD nanoassembly).

scholarly journals Proteolytic Remodeling of Perineuronal Nets: Effects on Synaptic Plasticity and Neuronal Population Dynamics

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
P. Lorenzo Bozzelli ◽  
Seham Alaiyed ◽  
Eunyoung Kim ◽  
Sonia Villapol ◽  
Katherine Conant
Keyword(s):  
Population Dynamics ◽  
Synaptic Plasticity ◽  
Synaptic Input ◽  
Neuronal Plasticity ◽  
Population Level ◽  
Gamma Oscillations ◽  
Brain Regions ◽  
Neuronal Population ◽  
Perineuronal Nets ◽  
Perineuronal Net

The perineuronal net (PNN) represents a lattice-like structure that is prominently expressed along the soma and proximal dendrites of parvalbumin- (PV-) positive interneurons in varied brain regions including the cortex and hippocampus. It is thus apposed to sites at which PV neurons receive synaptic input. Emerging evidence suggests that changes in PNN integrity may affect glutamatergic input to PV interneurons, a population that is critical for the expression of synchronous neuronal population discharges that occur with gamma oscillations and sharp-wave ripples. The present review is focused on the composition of PNNs, posttranslation modulation of PNN components by sulfation and proteolysis, PNN alterations in disease, and potential effects of PNN remodeling on neuronal plasticity at the single-cell and population level.

scholarly journals Connexin Hemichannel Mimetic Peptide Attenuates Cortical Interneuron Loss and Perineuronal Net Disruption Following Cerebral Ischemia in Near-Term Fetal Sheep

2020 ◽  
Vol 21 (18) ◽  
pp. 6475
Author(s):  
Panzao Yang ◽  
Joanne O. Davidson ◽  
Tania M. Fowke ◽  
Robert Galinsky ◽  
Guido Wassink ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Perineuronal Nets ◽  
Perinatal Hypoxia ◽  
Perineuronal Net ◽  
Fetal Sheep ◽  
Mimetic Peptide ◽  
Intracerebroventricular Infusion ◽  
Bilateral Carotid ◽  
Cortical Interneurons ◽  
Hypoxia Ischemia

Perinatal hypoxia-ischemia is associated with disruption of cortical gamma-aminobutyric acid (GABA)ergic interneurons and their surrounding perineuronal nets, which may contribute to persisting neurological deficits. Blockade of connexin43 hemichannels using a mimetic peptide can alleviate seizures and injury after hypoxia-ischemia. In this study, we tested the hypothesis that connexin43 hemichannel blockade improves the integrity of cortical interneurons and perineuronal nets. Term-equivalent fetal sheep received 30 min of bilateral carotid artery occlusion, recovery for 90 min, followed by a 25-h intracerebroventricular infusion of vehicle or a mimetic peptide that blocks connexin hemichannels or by a sham ischemia + vehicle infusion. Brain tissues were stained for interneuronal markers or perineuronal nets. Cerebral ischemia was associated with loss of cortical interneurons and perineuronal nets. The mimetic peptide infusion reduced loss of glutamic acid decarboxylase-, calretinin-, and parvalbumin-expressing interneurons and perineuronal nets. The interneuron and perineuronal net densities were negatively correlated with total seizure burden after ischemia. These data suggest that the opening of connexin43 hemichannels after perinatal hypoxia-ischemia causes loss of cortical interneurons and perineuronal nets and that this exacerbates seizures. Connexin43 hemichannel blockade may be an effective strategy to attenuate seizures and may improve long-term neurological outcomes after perinatal hypoxia-ischemia.

scholarly journals Functionalization of Gold Nanoparticles by Inorganic Entities

Nanomaterials ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 548 ◽  
Author(s):  
Frédéric Dumur ◽  
Eddy Dumas ◽  
Cédric R. Mayer
Keyword(s):  
Gold Nanoparticles ◽  
Rapid Development ◽  
Gold Surface ◽  
Intrinsic Properties ◽  
Au Nps ◽  
Gold Core ◽  
Inorganic Systems ◽  
Wide Range ◽  
Different Types ◽  
Electron Donating Groups

The great affinity of gold surface for numerous electron-donating groups has largely contributed to the rapid development of functionalized gold nanoparticles (Au-NPs). In the last years, a new subclass of nanocomposite has emerged, based on the association of inorganic molecular entities (IME) with Au-NPs. This highly extended and diversified subclass was promoted by the synergy between the intrinsic properties of the shell and the gold core. This review—divided into four main parts—focuses on an introductory section of the basic notions related to the stabilization of gold nanoparticles and defines in a second part the key role played by the functionalizing agent. Then, we present a wide range of inorganic molecular entities used to prepare these nanocomposites (NCs). In particular, we focus on four different types of inorganic systems, their topologies, and their current applications. Finally, the most recent applications are described before an overview of this new emerging field of research.

scholarly journals RNA Chemistry for RNA Biology

2019 ◽  
Vol 73 (5) ◽  
pp. 368-373 ◽  
Author(s):  
Pascal Röthlisberger ◽  
Christian Berk ◽  
Jonathan Hall
Keyword(s):  
Chemical Synthesis ◽  
Nucleic Acids ◽  
Chemical Biology ◽  
Rna Synthesis ◽  
Intrinsic Properties ◽  
Chemical Modifications ◽  
Chemically Modified ◽  
Wide Range ◽  
Rna Biology ◽  
Modified Nucleic Acids

Advances in the chemical synthesis of RNA have opened new possibilities to address current questions in RNA biology. Access to site-specifically modified oligoribonucleotides is often a pre-requisite for RNA chemical-biology projects. Driven by the enormous research efforts for development of oligonucleotide therapeutics, a wide range of chemical modifications have been developed to modulate the intrinsic properties of nucleic acids in order to fit their use as therapeutics or research tools. The RNA synthesis platform, supported by the NCCR RNA & Disease, aims to provide access to a large variety of chemically modified nucleic acids. In this review, we describe some of the recent projects that involved work of the platform and highlight how RNA chemistry supports new discoveries in RNA biology.

scholarly journals Effect of Age in Second Language Acquisition: A Critical Review from the Perspective of Critical Period Hypothesis and Ultimate Attainment

2017 ◽  
Vol 7 (5) ◽  
pp. 1 ◽  
Author(s):  
Mohammad Mosiur Rahman ◽  
Ambigapathy Pandian ◽  
Abdul Karim ◽  
Faheem Hasan Shahed
Keyword(s):  
Second Language ◽  
Second Language Acquisition ◽  
Language Acquisition ◽  
Critical Period ◽  
Secondary Data ◽  
Future Research ◽  
Critical Period Hypothesis ◽  
Wide Range ◽  
Ultimate Attainment ◽  
Effect Of Age

This article addresses the effect of age in Second Language Acquisition (SLA), posing the relative question that whether the Critical Period hypothesis (CPH) exists in Second Language (SL), and if existing, how it is associated duly with SLA. The justification of comparing the achievement of L1 and L2 learners on the basis of Ultimate Attainment (UA) in the establishment of Critical Period Hypothesis, is also discussed. In the methodology, secondary data analysis was used to answer of research questions. To achieve a reliable result from the wide range of secondary data primarily from journal articles, a systemic search has been adopted. In conclusion, compare and contrast was made with earlier studies to show the findings of the study and to scope future research. 

AGE OF ONSET AND NATIVELIKE L2 ULTIMATE ATTAINMENT OF MORPHOSYNTACTIC AND PHONETIC INTUITION

2012 ◽  
Vol 34 (2) ◽  
pp. 187-214 ◽  
Author(s):  
Niclas Abrahamsson
Keyword(s):  
Second Language ◽  
Adult Learners ◽  
Negative Correlation ◽  
Critical Period ◽  
Age Of Onset ◽  
L2 Proficiency ◽  
Critical Period Hypothesis ◽  
Wide Range ◽  
Ultimate Attainment ◽  
The Relationship

Research has consistently shown there is a negative correlation between age of onset (AO) of acquisition and ultimate attainment (UA) of either pronunciation or grammar in a second language (L2). A few studies have indeed reported nativelike behavior in some postpuberty learners with respect to either phonetics/phonology or morphosyntax, a result that has sometimes been taken as evidence against the critical period hypothesis (CPH). However, in the few studies that have employed a wide range of linguistic tests and tasks, adult learners have not exhibited nativelike L2 proficiency across the board of measures, which, according to some, suggests that the hypothesis still holds. The present study investigated the relationship between AO and UA and the incidence of nativelikeness when measures of phonetic and grammatical intuition are combined. An additional aim was to investigate whether children and adults develop the L2 through fundamentally different brain mechanisms—namely, whether children acquire the language (more) implicitly as an interdependent whole, whereas adults learn it (more) explicitly as independent parts of a whole.

scholarly journals Chondroitinase and antidepressants promote plasticity by releasing TRKB from dephosphorylating control of PTPσ in parvalbumin neurons

2020 ◽  
Author(s):  
Angelina Lesnikova ◽  
Plinio Cabrera Casarotto ◽  
Senem Merve Fred ◽  
Mikko Voipio ◽  
Frederike Winkel ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Protein Tyrosine Phosphatase ◽  
Critical Period ◽  
Antidepressant Treatment ◽  
Tyrosine Phosphatase ◽  
Adult Brain ◽  
Neurotrophin Receptor ◽  
Perineuronal Nets ◽  
Protein Tyrosine ◽  
Chondroitin Sulphate Proteoglycans

AbstractPerineuronal nets (PNNs) are an extracellular matrix structure rich in chondroitin sulphate proteoglycans (CSPGs) which preferentially encase parvalbumin-containing (PV+) interneurons. PNNs restrict cortical network plasticity but the molecular mechanisms involved are unclear. We found that reactivation of ocular dominance plasticity in the adult visual cortex induced by chondroitinase (chABC)-mediated PNN removal requires intact signaling by the neurotrophin receptor TRKB in PV+ neurons. Additionally, we demonstrate that chABC increases TRKB phosphorylation (pTRKB), while PNN component aggrecan attenuates BDNF-induced pTRKB in cortical neurons in culture. We further found that protein tyrosine phosphatase sigma (PTPσ, PTPRS), receptor for CSPGs, interacts with TRKB and restricts TRKB phosphorylation. PTPσ deletion increases phosphorylation of TRKB in vitro and in vivo in male and female mice, and juvenile-like plasticity is retained in the visual cortex of adult PTPσ deficient mice (PTPσ+/-). The antidepressant drug fluoxetine, which is known to promote TRKB phosphorylation and reopen critical period-like plasticity in the adult brain, disrupts the interaction between TRKB and PTPσ by binding to the transmembrane domain of TRKB. We propose that both chABC and fluoxetine reopen critical period-like plasticity in the adult visual cortex by promoting TRKB signaling in PV+ neurons through inhibition of TRKB dephosphorylation by the PTPσ-CSPG complex.Significance statementCritical period-like plasticity can be reactivated in the adult visual cortex through disruption of perineuronal nets (PNNs) by chondroitinase treatment, or by chronic antidepressant treatment. We now show that the effects of both chondroitinase and fluoxetine are mediated by the neurotrophin receptor TRKB in parvalbumin-containing (PV+) interneurons. We found that chondroitinase-induced visual cortical plasticity is dependent on TRKB in PV+ neurons. Protein tyrosine phosphatase type S (PTPσ, PTPRS), a receptor for PNNs, interacts with TRKB and inhibits its phosphorylation, and chondroitinase treatment or deletion of PTPσ increases TRKB phosphorylation. Antidepressant fluoxetine disrupts the interaction between TRKB and PTPσ, thereby increasing TRKB phosphorylation. Thus, juvenile-like plasticity induced by both chondroitinase and antidepressant treatment is mediated by TRKB activation in PV+ interneurons.

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