Histology and Neurobiology Unit (UHNeurob)

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The Research Group of the Histology and Neurobiology Unit, UHNeurob, has developed basic research in the field of Cellular Neurobiology for more than three decades. It aims to study the molecular mechanisms that regulate neurotransmission and synaptic connectivity. Of particular interest is the study of the intracellular signaling triggered by neurotrophic, muscarinic, purinergic and cannabinoid receptors and which converges in kinases to regulate neurotransmission. The synapse under study is the neuromuscular junction during development, maturity, aging and in pathologies such as amyotrophic lateral sclerosis (ALS) or spinal muscular atrophy (SMA). In addition, we study the impact of physical exercise and experimental pharmacological treatments as therapies to preserve and strengthen synapses and the neuromuscular system.

RESPONSIBLE
  • Dra. María Angel Lanuza

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The UHNeurob Group focuses its research on Cellular Neurobiology, in particular on the study of the basic mechanisms of activity-dependent synaptic regulation. Of particular interest is the study of the intracellular signaling that neurotrophic, muscarinic and purinergic and cannabinoid receptors trigger and that converges in kinases to regulate neurotransmission. The synapse under study is the neuromuscular junction.

With this idea, the group develops different lines of research with a common goal which is the knowledge of the mechanisms that regulate synaptic connectivity during development, maturity, aging and disease.

During development we study the mechanisms that direct the synaptic competition between neurons to innervate the same target cell. The consequence of this competition is the establishment of the adult pattern of stable but plastic synaptic connections, essential for learning and memory.

In the adult stage, the group is focused on the study of activity-dependent signaling pathways that regulate neurotransmission. The results in this area make it possible to understand the role of these pathways in the functioning of synapses and to determine which molecules could play a relevant role in pathologies that alter their normal functioning.

The UHNeurob group is also very interested in the study of the cellular and molecular mechanisms of neuromuscular diseases, particularly amyotrophic lateral sclerosis (ALS) and the impact of physical exercise as a therapy to preserve neuromuscular function. He also researches cellular and molecular changes in the neuromuscular system during aging. The final objective is, in both cases, the identification of therapeutic targets that prevent the disconnection and degeneration of the neuromuscular synapse to delay or prevent the neuronal degeneration that takes place in both cases. This research is of great interest to society since the preservation of the neuromuscular junction would improve the motor activities of the affected people.

At a technical level, methodological approaches are used in the field of microscopy, biochemistry and cellular and molecular biology, omics technologies and the evaluation of motor capacity. Rat and mouse animal models are used, some of them transgenic, and physical exercise and ex-vivo electrical stimulation techniques are applied to increase neuromuscular synaptic activity.

  • Cell neurobiology, synaptogenesis, mechanisms of regulation of synaptic activity and mechanisms of adaptation, remodeling and plasticity in the nervous system.
  • Intracellular signaling of neurotrophic, muscarinic, purinergic and cannabinoid receptors and associated kinases.
  • Retrograde regulation of neurotrophic signaling to maintain neuromuscular synapse homeostasis.
  • Molecular mechanisms that intervene and regulate synaptic transmission.
  • Regulatory mechanisms of synaptic connectivity during development, maturity, aging and disease. Configuration of neural circuits.
  • Cellular and molecular changes in the neuromuscular system during aging.
  • Cellular and molecular bases of neuromuscular diseases, in particular, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA).
  • Physical exercise as a regulatory therapy for the preservation and strengthening of the neuromuscular synapse in physiological and pathological conditions.
    Brain-derived neurotrophic factor (BDNF) signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

    Tomàs J, Cilleros-Mañé V, Just-Borràs L, Balanyà-Segura M, Polishchuk A, Nadal L, Tomàs M, Silvera-Simón C, Santafé MM, Lanuza MA
    Neural Regeneration Research, 19, 2024, in press.

    Synaptic retrograde regulation of the PKA-induced SNAP-25 and Synapsin-1 phosphorylation

    Polishchuk A, Cilleros-Mañé V, Just-Borràs L, Balanyà-Segura M, Vandellòs Pont G, Silvera Simón C, Tomàs M, Garcia N, Tomàs J, Lanuza MA.
    Cell Mol Biol Lett. 2023 Mar 3;28(1):17.
    Doi: 10.1186/s11658-023-00431-2.

    Muscarinic Receptors in Developmental Axonal Competition at the Neuromuscular Junction

    Tomàs J, Lanuza MA, Santafé MM, Cilleros-Mañé V, Just-Borràs L, Balanyà-Segura M, Polishchuk A, Nadal L, Tomàs M, Garcia N.
    Mol Neurobiol. 2023 Mar;60(3):1580-1593.
    Doi: 10.1007/s12035-022-03154-1.
    PMID: 36526930; PMCID: PMC9899176

    TrkB signaling is correlated with muscular fatigue resistance and less vulnerability to neurodegeneration

    Just-Borràs L, Cilleros-Mañé V, Polishchuk A, Balanyà-Segura M, Tomàs M, Garcia N, Tomàs J, Lanuza MA.
    Front Mol Neurosci. 2022. Dec 22;15:1069940.
    doi: 10.3389/fnmol.2022.1069940.

    Involvement of the Voltage-Gated Calcium Channels L- P/Q- and N-Types in Synapse Elimination During Neuromuscular Junction Development

    Garcia N, Hernández P, Lanuza MA, Tomàs M, Cilleros-Mañé V, Just-Borràs L, Duran-Vigara M, Polishchuk A, Balanyà-Segura M, Tomàs J.
    Mol Neurobiol. 2022 Jul;59(7):4044-4064.
    doi: 10.1007/s12035-022-02818-2.

    PKA and PKC Balance in Synapse Elimination during Neuromuscular Junction Development

    Garcia N, Lanuza MA, Tomàs M, Cilleros-Mañé V, Just-Borràs L, Duran M, Polishchuk A, Tomàs J.
    Cells. 2021 Jun 4;10(6):1384.
    doi: 10.3390/cells10061384.

    M1 and M2 mAChRs activate PDK1 and regulate PKC βI and ε and the exocytotic apparatus at the NMJ

    Cilleros-Mañé V, Just-Borràs L, Polishchuk A, Durán M, Tomàs M, Garcia N, Tomàs JM, Lanuza MA.
    FASEB J. 2021 Jul;35(7):e21724.
    doi: 10.1096/fj.202002213R.

    Running and Swimming Differently Adapt the BDNF/TrkB Pathway to a Slow Molecular Pattern at the NMJ

    Just-Borràs L, Cilleros-Mañé V, Hurtado E, Biondi O, Charbonnier F, Tomàs M, Garcia N, Tomàs J, Lanuza MA.
    Int J Mol Sci. 2021, Apr 27;22(9):4577.
    doi: 10.3390/ijms22094577.

    The M2 muscarinic receptor, in association to M1, regulates the neuromuscular PKA molecular dynamics

    Cilleros-Mañé V, Just-Borràs L, Tomàs M, Garcia N, Tomàs JM, Lanuza MA.
    FASEB J. 2020 Apr;34(4):4934-4955.
    doi: 10.1096/fj.201902113R.

    Running and swimming prevent the deregulation of the BDNF/TrkB neurotrophic signalling at the neuromuscular junction in mice with amyotrophic lateral sclerosis

    Just-Borràs L, Hurtado E, Cilleros-Mañé V, Biondi O, Charbonnier F, Tomàs M,
    Garcia N, Tomàs J, Lanuza MA.
    Cell Mol Life Sci. 2020 Aug;77(15):3027-3040.
    doi: 10.1007/s00018-019-03337-5.

    Overview of Impaired BDNF Signaling, Their Coupled Downstream Serine-Threonine Kinases and SNARE/SM Complex in the Neuromuscular Junction of the Amyotrophic Lateral Sclerosis Model SOD1-G93A Mice

    Just-Borràs L, Hurtado E, Cilleros-Mañé V, Biondi O, Charbonnier F, Tomàs M,
    Garcia N, Lanuza MA, Tomàs J.
    Mol Neurobiol. 2019 Oct;56(10):6856-6872.
    doi: 10.1007/s12035-019-1550-1.

    nPKCε Mediates SNAP-25 Phosphorylation of Ser-187 in Basal Conditions and After Synaptic Activity at the Neuromuscular Junction

    Simó A, Cilleros-Mañé V, Just-Borràs L, Hurtado E, Nadal L, Tomàs M, Garcia N, Lanuza MA, Tomàs J.
    Mol Neurobiol. 2019 Aug;56(8):5346-5364.
    doi: 10.1007/s12035-018-1462-5.

    The Impact of Kinases in Amyotrophic Lateral Sclerosis at the Neuromuscular Synapse: Insights into BDNF/TrkB and PKC Signaling

    Lanuza MA, Just-Borràs L, Hurtado E, Cilleros-Mañé V, Tomàs M, Garcia N, Tomàs J.
    Cells. 2019, Dec 5;8(12):1578.
    doi: 10.3390/cells8121578.

    Opposed Actions of PKA Isozymes (RI and RII) and PKC Isoforms (cPKCβI and nPKCε) in Neuromuscular Developmental Synapse Elimination

    Garcia N, Balañà C, Lanuza MA, Tomàs M, Cilleros-Mañé V, Just-Borràs L, Tomàs J.
    Cells. 2019 Oct 23;8(11):1304.
    doi: 10.3390/cells8111304.

    Adenosine Receptors in Developing and Adult Mouse Neuromuscular Junctions and Functional Links With Other Metabotropic Receptor Pathways

    Tomàs J, Garcia N, Lanuza MA, Santafé MM, Tomàs M, Nadal L, Hurtado E, Simó-Ollé A, Cilleros-Mañé V, Just-Borràs
    L.Front Pharmacol. 2018 Apr 24;9:397.
    doi: 10.3389/fphar.2018.00397.

    BDNF-TrkB Signaling Coupled to nPKCε and cPKCβI Modulate the Phosphorylation of the Exocytotic Protein Munc18-1 During Synaptic Activity at the Neuromuscular Junction

    Simó A, Just-Borràs L, Cilleros-Mañé V, Hurtado E, Nadal L, Tomàs M, Garcia N, Lanuza MA, Tomàs J.
    Front Mol Neurosci. 2018 Jun 12;11:207.
    doi: 10.3389/fnmol.2018.00207.

  • Tomàs JM, Garcia N, Lanuza MA, Nadal L, Tomàs M, Hurtado E, Simó A, Cilleros V. “Membrane receptor-induced changes of the protein kinases A and C activity may play a leading role in promoting developmental synapse elimination at the neuromuscular junction”. In: Synaptic Assembly and Neural Circuit Development. Ko, J., Zhang, C., eds (2018). Lausanne: Frontiers Media. ISSN 1664-8714, ISBN 978-2-88945-630-7, doi: 10.3389/978-2-88945-630-7. pp 124-132.

  • Tomàs JM, Garcia N, Lanuza MA, Santafé MM, Tomàs M, Nadal L, Hurtado E, Simó A, Cilleros V. “Presynaptic Membrane Receptors Modulate ACh Release, Axonal Competition and Synapse Elimination during Neuromuscular Junction Development” In: Synaptic Assembly and Neural Circuit Development. Ko, J., Zhang, C., eds (2018). Lausanne: Frontiers Media. ISSN 1664-8714, ISBN 978-2-88945-630-7, doi: 10.3389/978-2-88945-630-7. pp 157-168.

  • Activity-dependent retrograde regulation of the neurotrophic signaling pathways to maintain homeostasis of the neuromuscular synapse. Role in Amyotrophic Lateral Sclerosis

    PID2022-141252NB-I00
    Funding entity: Ministerio de Ciencia e Innovación.
    Duration: 31/08/2023 – 30/08/2026.
    Principal investigator: Lanuza Escolano, Maria Angel

  • 2021 SGR 01214 Suport a grups de recerca (SGR) URV – Grup de recerca consolidat

    Funding entity: Agència de Gestió d’Ajuts Universitaris i de Recerca.
    Duration: 2023 – 2025
    Principal investigator: Lanuza Escolano, Maria Angel

  • Effect of neuromuscular activity on muscarinic and neurotrophic synaptic signaling. Implication in Amyotrophic Lateral Sclerosis

    PID2019-106332GB-I00
    Funding entity: Ministerio de Ciencia, Innovación y Universidades.
    Duration: 31/05/2020 – 30/05/2024.
    Principal investigator: Lanuza Escolano, Maria Angel / Tomàs Ferré, Josep

  • Muscle activity and retrograde control of neurotransmission: effect of BDNF/TrkB/PKC signaling on synaptic vesicle proteins

    SAF2015-67143-P
    Funding entity: Ministerio de Economía y Competitividad.
    Duration: 01/01/2016 – 31/12/2018.
    Principal investigator: Tomàs Ferré, Josep / Lanuza Escolano, Maria Angel

  • Effect of neuromuscular activity on muscarinic and neurotrophic synaptic signaling. Implication in Amyotrophic Lateral Sclerosis

    PRE2020-092084
    Funding entity: Ministerio de Ciencia e Innovación.
    Duration: 31/08/2021 – 30/08/2025.
    Principal investigator: Lanuza Escolano, María Angel

  • Effect of neuromuscular activity on muscarinic and neurotrophic synaptic signaling in aging

    2023 FI_3 00176.
    Funding entity: Agència de Gestió d’Ajuts Universitaris i de Recerca.
    Duration: 30/04/2021 – 29/04/2025.
    Principal investigator: Lanuza Escolano, Maria Angel.

  • 2017 SGR 00704 Suport a grups de recerca (SGR) URV – Grup de recerca consolidat

    Funding entity: Agència de Gestió d’Ajuts Universitaris i de Recerca.
    Duration: 2017 – 2022
    Principal investigator: Tomàs Ferré, Josep

  • Formación e implicación en las actividades técnicas de laboratorio de la Unidad docente e investigadora de Histología y Neurobiología de la Facultad de Medicina y Ciencias de la Salud de la Universitat Rovira i Virgili

    PEJ2018-002805-A-MINECO.
    Funding entity: Ministerio de Ciencia, Innovación y Universidades / Universitat Rovira i Virgili.
    Duration: 31/08/2019 – 30/08/2022.
    Investigador Principal: Tomás Ferré, Josep

  • Neurotrophic factors and receptors assessment in P10 SMA mice under BIO101 treatment

    T22364S.
    Contract Company: Biophytis, SA (París, France)
    Duration: 17/10/2022 – 15/02/2024
    Principal investigator: Lanuza Escolano, Maria Angel.

  • Els antioxidants derivats de les llavors del raïm com molècules preventives en l’envelliment del sistema neuromuscular

    2022PRD-DIPTA-URV20
    Contract Company: Diputació de Tarragona
    Duration: 01/01/2022 – 31/12/2023.
    Investigador Principal: Garcia Sancho, Neus / Lanuza Escolano, Maria Angel

Team Members

  • Responsable de grup

    • Dra. María Angel Lanuza
  • Investigadors sèniors

    • Josep Maria Tomàs
    • Rosa Fenoll Brunet
    • Marta Tomàs
  • Investigadores post doctorals

    • Laia Just
    • Erica Hurtado
  • Tècnica

    • Carolina Silvera
  • Investigadors predoctorals en formació

    • Marta Balanyà
    • Aleksandra Polishchuck
    • Meryem Jami El Hirchi