Parvalbumin Interneurons and Perineuronal Nets in the Hippocampus and Retrosplenial Cortex of Adult Male Mice After Early Social Isolation Stress and Perinatal NMDA Receptor Antagonist Treatment DOI Creative Commons
Patrycja Klimczak, Arianna Rizzo, Esther Castillo‐Gomez

et al.

Frontiers in Synaptic Neuroscience, Journal Year: 2021, Volume and Issue: 13

Published: Sept. 22, 2021

Both early life aversive experiences and intrinsic alterations in postnatal neurodevelopment are considered predisposing factors for psychiatric disorders, such as schizophrenia. The prefrontal cortex the hippocampus have protracted development affected schizophrenic patients. Interestingly, similar been observed retrosplenial (RSC). Studies patients animal models of schizophrenia found cortical parvalbumin (PV) expressing interneurons, making them good candidates to study etiopathology this disorder. Some PV+ interneurons may be mediated by perineuronal nets (PNNs), specialized regions extracellular matrix, which frequently surround these inhibitory neurons. In study, we used a double hit model (DHM) combining single perinatal injection an NMDAR antagonist (MK801) disturb post-weaning social isolation experience. We investigated PV PNNs RSC adult male mice, using unbiased stereology. CA1, but not CA3 region, hippocampus, number + PNN+ cells was drug treatment, significant decrease parameters groups animals that received MK801. percentage surrounding significantly decreased after treatment both hippocampal regions; however, impact only where isolated presented lower percentages. , effects isolation, MK801 interaction interventions on studied parameters; DHM, PV+, PNNs, PV+PNN+cells when compared control mice. Similar decreases were just or treated with To our knowledge, is first report neurodevelopmental during infancy/adolescence. These results show early-life events different regions, especially structure plasticity neurons their involvement emergence certain disorders.

Language: Английский

The extracellular matrix and perineuronal nets in memory DOI Creative Commons
James W. Fawcett, Marianne Fyhn, Pavla Jendelová

et al.

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(8), P. 3192 - 3203

Published: June 27, 2022

Abstract All components of the CNS are surrounded by a diffuse extracellular matrix (ECM) containing chondroitin sulphate proteoglycans (CSPGs), heparan (HSPGs), hyaluronan, various glycoproteins including tenascins and thrombospondin, many other molecules that secreted into ECM bind to components. In addition, some neurons, particularly inhibitory GABAergic parvalbumin-positive (PV) interneurons, more condensed cartilage-like called perineuronal nets (PNNs). PNNs surround soma proximal dendrites as net-like structures synapses. Attention has focused on role in control plasticity, but it is now clear also play an important part modulation memory. this review we summarize ECM, PNNs, types memory their participation pathology. being considered target for treatment impaired There potential targets mainly through sulphation, binding, production CSPGs they contain or digestion sulphated glycosaminoglycans.

Language: Английский

Citations

99
A comprehensive atlas of perineuronal net distribution and colocalization with parvalbumin in the adult mouse brain DOI Creative Commons
Leonardo Lupori, Valentino Totaro, Sara Cornuti

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(7), P. 112788 - 112788

Published: July 1, 2023

Perineuronal nets (PNNs) surround specific neurons in the brain and are involved various forms of plasticity clinical conditions. However, our understanding PNN role these phenomena is limited by lack highly quantitative maps distribution association with cell types. Here, we present a comprehensive atlas Wisteria floribunda agglutinin (WFA)-positive PNNs colocalization parvalbumin (PV) cells for over 600 regions adult mouse brain. Data analysis shows that PV expression good predictor aggregation. In cortex, dramatically enriched layer 4 all primary sensory areas correlation thalamocortical input density, their mirrors intracortical connectivity patterns. Gene identifies many PNN-correlated genes. Strikingly, PNN-anticorrelated transcripts synaptic genes, generalizing PNNs' as circuit stability factors.

Language: Английский

Citations

45
The excitatory-inhibitory balance as a target for the development of novel drugs to treat schizophrenia DOI
Daniela L. Uliana,

João Roberto Lisboa,

Felipe V. Gomes

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 228, P. 116298 - 116298

Published: May 21, 2024

Language: Английский

Citations

18
A glial perspective on the extracellular matrix and perineuronal net remodeling in the central nervous system DOI Creative Commons
Bhanu P. Tewari, Lata Chaunsali, Courtney Prim

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: Oct. 20, 2022

A structural scaffold embedding brain cells and vasculature is known as extracellular matrix (ECM). The physical appearance of ECM in the central nervous system (CNS) ranges from a diffused, homogeneous, amorphous, nearly omnipresent to highly organized distinct morphologies such basement membranes perineuronal nets (PNNs). changes its composition organization during development, adulthood, aging, several CNS pathologies. This spatiotemporal dynamic nature PNNs brings unique versatility their functions spanning neurogenesis, cell migration differentiation, axonal growth, pathfinding cues, etc., developing brain, stabilizing synapses, neuromodulation, being an active partner tetrapartite synapses adult brain. malleability governed by both intrinsic extrinsic factors. Glial are among major factors that facilitate remodeling PNN, thereby acting key regulators diverse PNN health diseases. In this review, we discuss recent advances our understanding how glial normal pathological states CNS.

Language: Английский

Citations

52
Differential impacts of germline and adult aggrecan knockout in PV+ neurons on perineuronal nets and PV+ neuronal function DOI Creative Commons
Sverre Grødem,

Elise Holter Thompson,

Malin Benum Røe

et al.

Molecular Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract Perineuronal nets (PNNs) are a condensed form of extracellular matrix primarily found around parvalbumin-expressing (PV+) interneurons. The postnatal maturation PV+ neurons is accompanied with the formation PNNs and reduced plasticity. Alterations in PNN neuron function have been described for mental disorders such as schizophrenia autism. highly dependent on aggrecan, proteoglycan encoded by ACAN gene, but it remains unknown if produced themselves. Thus, we established knockout (KO) mouse model (ACANflx/PVcre) an adeno-associated virus to specifically eliminate aggrecan production from neurons, germline or adult animals, respectively. KO eliminated expression labeled Wisteria floribunda agglutinin (WFA), most commonly used marker. Surprisingly, electrophysiological properties interneurons ocular dominance plasticity ACANflx/PVcre mice were similar controls. In contrast, AAV-mediated increased Moreover, vivo Chondroitinase ABC treatment resulted firing rate cells frequency spontaneous excitatory postsynaptic currents (sEPSC), phenotype associated chABC WT animals. These findings suggest that compensatory mechanisms may be activated during development response loss aggrecan. Indeed, qPCR bulk tissue indicates other components, including neurocan tenascin-R, expressed at higher levels Finally, behavioral testing revealed had long-term memory controls Morris water maze. However, they employed bolder search strategies spatial learning showed lower level anxiety-related behavior open field zero

Language: Английский

Citations

1
Parvalbumin interneuron alterations in stress-related mood disorders: A systematic review DOI Creative Commons
George Perlman, Arnaud Tanti, Naguib Mechawar

et al.

Neurobiology of Stress, Journal Year: 2021, Volume and Issue: 15, P. 100380 - 100380

Published: Aug. 12, 2021

Stress-related psychiatric disorders including depression involve complex cellular and molecular changes in the brain, GABAergic signaling dysfunction is increasingly implicated etiology of mood disorders. Parvalbumin (PV)-expressing neurons are fast-spiking interneurons that, among other roles, coordinate synchronous neuronal firing. Mounting evidence suggests that PV neuron phenotype altered by stress In this systematic review, we assessed interneuron alterations as reported human postmortem brain studies animal models environmental stress. This review aims to 1) comprehensively catalog cell function (humans) (animals); 2) analyze strength various regions humans rodents; 3) determine whether modulating effect antidepressant treatment, physical exercise, enrichment on animals associates with particular effects function; 4) use information guide future research avenues. Its principal findings, derived mainly from rodent studies, stress-related cells only a minority positive findings region-, age-, sex-, recency-dependent, antidepressants protect stress-induced apparent loss. These observations do not currently translate well humans, although literature topic remains limited.

Language: Английский

Citations

45
Gabaergic Interneurons in Early Brain Development: Conducting and Orchestrated by Cortical Network Activity DOI Creative Commons

Davide Warm,

Jonas Schroer,

Anne Sinning

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: Jan. 3, 2022

Throughout early phases of brain development, the two main neural signaling mechanisms-excitation and inhibition-are dynamically sculpted in neocortex to establish primary functions. Despite its relatively late formation persistent developmental changes, GABAergic system promotes ordered shaping neuronal circuits at structural functional levels. Within this frame, interneurons participate first spontaneous later sensory-evoked activity patterns that precede cortical functions mature brain. Upon their subcortical generation, embryonic must orderly migrate settle respective target layers before they can actively engage network activity. During process, changes molecular synaptic level allow not only coordinated but also pruning connections as well excitatory inhibitory synapses. At postsynaptic site, shift from an towards response is required enable synchronization within networks. Concomitantly, progressive specification different interneuron subtypes endows with distinct local region-specific modulation firing. Finally, apoptotic process further refines populations by constantly maintaining a controlled ratio neurons. Interestingly, many these fundamental complex processes are influenced-if directly controlled-by electrical Interneurons on subcellular, cellular, affected high frequency patterns, such spindle burst gamma oscillations rodents delta brushes humans. Conversely, maturation structure function each scales feeds back contributes generation essential for proper peri- postnatal development. Overall, more precise description conducting role terms how contribute specific patterns-as impinge orchestra members-will lead better understanding physiological pathophysiological development nervous system.

Language: Английский

Citations

37
Extracellular matrix abnormalities in the hippocampus of subjects with substance use disorder DOI Creative Commons

Jake Valeri,

Charlotte Stiplosek,

Sinead M. O’Donovan

et al.

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: Feb. 24, 2024

Contextual triggers are significant factors contributing to relapse in substance use disorders (SUD). Emerging evidence points a critical role of extracellular matrix (ECM) molecules as mediators reward memories. Chondroitin sulfate proteoglycans (CSPGs) subset ECM that form perineuronal nets (PNN) around inhibitory neurons. PNNs restrict synaptic connections and help maintain synapses. Rodent models suggest modulation may strengthen contextual memories SUD. However, there is currently lack information regarding the hippocampus people with SUD well how comorbidity major depressive disorder (MDD) affect PNNs. We used postmortem hippocampal tissues from cohorts human nonhuman primates or without chronic alcohol test hypothesis increased subjects histochemical labeling quantitative microscopy examine PNNs, qRT-PCR gene expression for molecules, markers related markers. identified densities CSPG-labeled glial cells SUD, coinciding decreased protease metalloproteinase 9 (Mmp9), excitatory marker vesicle associated membrane protein 2 (Vamp2). Similar increases were observed monkeys self-administration. Subjects MDD displayed changes opposite comorbid had minimal any outcome measures examined. Our findings demonstrate possibly stabilizing suggested by preclinical studies. results also point previously unsuspected CSPG Evidence suggests targeting weaken promising therapeutic approach however consideration.

Language: Английский

Citations

7
How Stress Influences the Dynamic Plasticity of the Brain’s Extracellular Matrix DOI Creative Commons
Blake J. Laham, Elizabeth Gould

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 15

Published: Jan. 25, 2022

Diffuse and structured extracellular matrix (ECM) comprise ∼20% of the brain’s volume play important roles in development adult plasticity. Perineuronal nets (PNNs), specialized ECM structures that surround certain types neurons brain, emerge during postnatal period, making their maintenance potentially sensitive to experience. Recent studies have shown stress affects diffuse as well PNNs, such effects are dependent on life stage brain region. Given participates synaptic plasticity, generation neuronal oscillations, synchronous firing across regions, all which been linked cognition emotional regulation, components may be candidate therapeutic targets for stress-induced neuropsychiatric disease. This review considers influence over with a focus functional outcomes potential translational relevance.

Language: Английский

Citations

26
The mechanisms of perineuronal net abnormalities in contributing aging and neurological diseases DOI
Yixiao Dong,

Kunkun Zhao,

Xuemei Qin

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 92, P. 102092 - 102092

Published: Oct. 13, 2023

Language: Английский

Citations

16