Absence of parvalbumin increases mitochondria volume and branching of dendrites in inhibitory Pvalb neurons in vivo: a point of convergence of autism spectrum disorder (ASD) risk gene phenotypes / Lucia JANICKOVA in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) . - 47 p. Titre : Absence of parvalbumin increases mitochondria volume and branching of dendrites in inhibitory Pvalb neurons in vivo: a point of convergence of autism spectrum disorder (ASD) risk gene phenotypes Type de document : Texte imprimé et/ou numérique Auteurs : Lucia JANICKOVA, Auteur ; Karin Farah RECHBERGER, Auteur ; Lucas WEY, Auteur ; Beat SCHWALLER, Auteur Article en page(s) : 47 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Calcium homeostasis  Calcium-binding protein  Mitochondria  Parvalbumin  Pvalb neurons Index. décimale : PER Périodiques Résumé : BACKGROUND: In fast firing, parvalbumin (PV)-expressing (Pvalb) interneurons, PV acts as an intracellular Ca(2+) signal modulator with slow-onset kinetics. In Purkinje cells of PV(-/-) mice, adaptive/homeostatic mechanisms lead to an increase in mitochondria, organelles equally capable of delayed Ca(2+) sequestering/buffering. An inverse regulation of PV and mitochondria likewise operates in cell model systems in vitro including myotubes, epithelial cells, and oligodendrocyte-like cells overexpressing PV. Whether such opposite regulation pertains to all Pvalb neurons is currently unknown. In oligodendrocyte-like cells, PV additionally decreases growth and branching of processes in a cell-autonomous manner. METHODS: The in vivo effects of absence of PV were investigated in inhibitory Pvalb neurons expressing EGFP, present in the somatosensory and medial prefrontal cortex, striatum, thalamic reticular nucleus, hippocampal regions DG, CA3, and CA1 and cerebellum of mice either wild-type or knockout (PV(-/-)) for the Pvalb gene. Changes in Pvalb neuron morphology and PV concentrations were determined using immunofluorescence, followed by 3D-reconstruction and quantitative image analyses. RESULTS: PV deficiency led to an increase in mitochondria volume and density in the soma; the magnitude of the effect was positively correlated with the estimated PV concentrations in the various Pvalb neuron subpopulations in wild-type neurons. The increase in dendrite length and branching, as well as thickness of proximal dendrites of selected PV(-/-) Pvalb neurons is likely the result of the observed increased density and length of mitochondria in these PV(-/-) Pvalb neuron dendrites. The increased branching and soma size directly linked to the absence of PV is assumed to contribute to the increased volume of the neocortex present in juvenile PV(-/-) mice. The extended dendritic branching is in line with the hypothesis of local hyperconnectivity in autism spectrum disorder (ASD) and ASD mouse models including PV(-/-) mice, which display all ASD core symptoms and several comorbidities including cortical macrocephaly at juvenile age. CONCLUSION: PV is involved in most proposed mechanisms implicated in ASD etiology: alterations in Ca(2+) signaling affecting E/I balance, changes in mitochondria structure/function, and increased dendritic length and branching, possibly resulting in local hyperconnectivity, all in a likely cell autonomous way. En ligne : http://dx.doi.org/10.1186/s13229-020-00323-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427 [article] Absence of parvalbumin increases mitochondria volume and branching of dendrites in inhibitory Pvalb neurons in vivo: a point of convergence of autism spectrum disorder (ASD) risk gene phenotypes [Texte imprimé et/ou numérique] / Lucia JANICKOVA, Auteur ; Karin Farah RECHBERGER, Auteur ; Lucas WEY, Auteur ; Beat SCHWALLER, Auteur . - 47 p. Langues : Anglais (eng) in Molecular Autism > 11 (2020) . - 47 p. Mots-clés : Autism spectrum disorder  Calcium homeostasis  Calcium-binding protein  Mitochondria  Parvalbumin  Pvalb neurons Index. décimale : PER Périodiques Résumé : BACKGROUND: In fast firing, parvalbumin (PV)-expressing (Pvalb) interneurons, PV acts as an intracellular Ca(2+) signal modulator with slow-onset kinetics. In Purkinje cells of PV(-/-) mice, adaptive/homeostatic mechanisms lead to an increase in mitochondria, organelles equally capable of delayed Ca(2+) sequestering/buffering. An inverse regulation of PV and mitochondria likewise operates in cell model systems in vitro including myotubes, epithelial cells, and oligodendrocyte-like cells overexpressing PV. Whether such opposite regulation pertains to all Pvalb neurons is currently unknown. In oligodendrocyte-like cells, PV additionally decreases growth and branching of processes in a cell-autonomous manner. METHODS: The in vivo effects of absence of PV were investigated in inhibitory Pvalb neurons expressing EGFP, present in the somatosensory and medial prefrontal cortex, striatum, thalamic reticular nucleus, hippocampal regions DG, CA3, and CA1 and cerebellum of mice either wild-type or knockout (PV(-/-)) for the Pvalb gene. Changes in Pvalb neuron morphology and PV concentrations were determined using immunofluorescence, followed by 3D-reconstruction and quantitative image analyses. RESULTS: PV deficiency led to an increase in mitochondria volume and density in the soma; the magnitude of the effect was positively correlated with the estimated PV concentrations in the various Pvalb neuron subpopulations in wild-type neurons. The increase in dendrite length and branching, as well as thickness of proximal dendrites of selected PV(-/-) Pvalb neurons is likely the result of the observed increased density and length of mitochondria in these PV(-/-) Pvalb neuron dendrites. The increased branching and soma size directly linked to the absence of PV is assumed to contribute to the increased volume of the neocortex present in juvenile PV(-/-) mice. The extended dendritic branching is in line with the hypothesis of local hyperconnectivity in autism spectrum disorder (ASD) and ASD mouse models including PV(-/-) mice, which display all ASD core symptoms and several comorbidities including cortical macrocephaly at juvenile age. CONCLUSION: PV is involved in most proposed mechanisms implicated in ASD etiology: alterations in Ca(2+) signaling affecting E/I balance, changes in mitochondria structure/function, and increased dendritic length and branching, possibly resulting in local hyperconnectivity, all in a likely cell autonomous way. En ligne : http://dx.doi.org/10.1186/s13229-020-00323-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427

Correction to: Absence of parvalbumin increases mitochondria volume and branching of dendrites in inhibitory Pvalb neurons in vivo: a point of convergence of autism spectrum disorder (ASD) risk gene phenotypes / Lucia JANICKOVA in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 7p. Titre : Correction to: Absence of parvalbumin increases mitochondria volume and branching of dendrites in inhibitory Pvalb neurons in vivo: a point of convergence of autism spectrum disorder (ASD) risk gene phenotypes Type de document : Texte imprimé et/ou numérique Auteurs : Lucia JANICKOVA, Auteur ; Karin Farah RECHBERGER, Auteur ; Lucas WEY, Auteur ; Beat SCHWALLER, Auteur Article en page(s) : 7p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-020-00404-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442 [article] Correction to: Absence of parvalbumin increases mitochondria volume and branching of dendrites in inhibitory Pvalb neurons in vivo: a point of convergence of autism spectrum disorder (ASD) risk gene phenotypes [Texte imprimé et/ou numérique] / Lucia JANICKOVA, Auteur ; Karin Farah RECHBERGER, Auteur ; Lucas WEY, Auteur ; Beat SCHWALLER, Auteur . - 7p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 7p. Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-020-00404-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=442

Profiling parvalbumin interneurons using iPSC: challenges and perspectives for Autism Spectrum Disorder (ASD) / Federica FILICE in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) . - 10 p. Titre : Profiling parvalbumin interneurons using iPSC: challenges and perspectives for Autism Spectrum Disorder (ASD) Type de document : Texte imprimé et/ou numérique Auteurs : Federica FILICE, Auteur ; Beat SCHWALLER, Auteur ; Tanja M. MICHEL, Auteur ; Edna GRÜNBLATT, Auteur Article en page(s) : 10 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  CRISPR-Cas9 technology  GABAergic  Induced pluripotent stem cells  Interneuron  Parvalbumin  Schizophrenia Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) are persistent conditions resulting from disrupted/altered neurodevelopment. ASD multifactorial etiology-and its numerous comorbid conditions-heightens the difficulty in identifying its underlying causes, thus obstructing the development of effective therapies. Increasing evidence from both animal and human studies suggests an altered functioning of the parvalbumin (PV)-expressing inhibitory interneurons as a common and possibly unifying pathway for some forms of ASD. PV-expressing interneurons (short: PVALB neurons) are critically implicated in the regulation of cortical networks' activity. Their particular connectivity patterns, i.e., their preferential targeting of perisomatic regions and axon initial segments of pyramidal cells, as well as their reciprocal connections, enable PVALB neurons to exert a fine-tuned control of, e.g., spike timing, resulting in the generation and modulation of rhythms in the gamma range, which are important for sensory perception and attention.New methodologies such as induced pluripotent stem cells (iPSC) and genome-editing techniques (CRISPR/Cas9) have proven to be valuable tools to get mechanistic insight in neurodevelopmental and/or neurodegenerative and neuropsychiatric diseases. Such technological advances have enabled the generation of PVALB neurons from iPSC. Tagging of these neurons would allow following their fate during the development, from precursor cells to differentiated (and functional) PVALB neurons. Also, it would enable a better understanding of PVALB neuron function, using either iPSC from healthy donors or ASD patients with known mutations in ASD risk genes. In this concept paper, the strategies hopefully leading to a better understanding of PVALB neuron function(s) are briefly discussed. We envision that such an iPSC-based approach combined with emerging (genetic) technologies may offer the opportunity to investigate in detail the role of PVALB neurons and PV during "neurodevelopment ex vivo." En ligne : http://dx.doi.org/10.1186/s13229-020-0314-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427 [article] Profiling parvalbumin interneurons using iPSC: challenges and perspectives for Autism Spectrum Disorder (ASD) [Texte imprimé et/ou numérique] / Federica FILICE, Auteur ; Beat SCHWALLER, Auteur ; Tanja M. MICHEL, Auteur ; Edna GRÜNBLATT, Auteur . - 10 p. Langues : Anglais (eng) in Molecular Autism > 11 (2020) . - 10 p. Mots-clés : Autism spectrum disorder  CRISPR-Cas9 technology  GABAergic  Induced pluripotent stem cells  Interneuron  Parvalbumin  Schizophrenia Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) are persistent conditions resulting from disrupted/altered neurodevelopment. ASD multifactorial etiology-and its numerous comorbid conditions-heightens the difficulty in identifying its underlying causes, thus obstructing the development of effective therapies. Increasing evidence from both animal and human studies suggests an altered functioning of the parvalbumin (PV)-expressing inhibitory interneurons as a common and possibly unifying pathway for some forms of ASD. PV-expressing interneurons (short: PVALB neurons) are critically implicated in the regulation of cortical networks' activity. Their particular connectivity patterns, i.e., their preferential targeting of perisomatic regions and axon initial segments of pyramidal cells, as well as their reciprocal connections, enable PVALB neurons to exert a fine-tuned control of, e.g., spike timing, resulting in the generation and modulation of rhythms in the gamma range, which are important for sensory perception and attention.New methodologies such as induced pluripotent stem cells (iPSC) and genome-editing techniques (CRISPR/Cas9) have proven to be valuable tools to get mechanistic insight in neurodevelopmental and/or neurodegenerative and neuropsychiatric diseases. Such technological advances have enabled the generation of PVALB neurons from iPSC. Tagging of these neurons would allow following their fate during the development, from precursor cells to differentiated (and functional) PVALB neurons. Also, it would enable a better understanding of PVALB neuron function, using either iPSC from healthy donors or ASD patients with known mutations in ASD risk genes. In this concept paper, the strategies hopefully leading to a better understanding of PVALB neuron function(s) are briefly discussed. We envision that such an iPSC-based approach combined with emerging (genetic) technologies may offer the opportunity to investigate in detail the role of PVALB neurons and PV during "neurodevelopment ex vivo." En ligne : http://dx.doi.org/10.1186/s13229-020-0314-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427

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