MECHANISMS INVOLVED IN AXONAL DEGENERATION

 

Our lab studies the molecular mechanisms underlying axonal degeneration. Axonal degeneration is a normal process during development of the nervous system, as is also observed as a primary event in the curse of neurodegenerative diseases. Hence, understanding how axons initiate and execute this process is of mayor interest and is an active area of intense research.

In previous studies we have shown a clear role for the proteases Caspasas and its regulators, the IAPs, in developmental axonal degeneration of sensory neurons (Unsain et al., 2013). One of our current interests is now evaluate if the mechanisms described for development are also taking place in neurodegenerative diseases.  To do so, we use primary neuronal cultures exposed to components that induce axonal degeneration and has been link with the etiology of Alzheirmer’s and Parkinson’s disease. To evaluate the role of the proteins of interest, we use modern genetic and molecular manipulations.

Another research interest of our lab is to understand the modification suffered by the cytoskeleton of actin and tubulin in the induction and execution of the degenerative process that yield to axonal fragmentation. For that porpoise, we use the most advanced microscopy techniques in combination with molecular and pharmacological manipulations to investigate the processes of interest.

As well, we are developing Expansion Microscopy techniques to reach resolution bellow the diffraction limit of light using conventional fluorescent microscopes.

For most of our approaches, we have modified a neuronal culture technique to be able to obtain isolated axons that are undergoing degeneration in order to perform detailed biochemical determinations (Unsain et al., 2014).

 

STUDENTS

Nahir Guadalupe Gazal

Becaria doctoral CONICET

nggazal@immf.uncor.edu

 

Agustina Bruno Vignolo

Estudiante de Grado (Universidad Nacional de Misiones)

agustinabrunovignolo@gmail.com

 

Julieta Marìa Sosa

Estudiante de Grado (Universidad Nacional de Córdoba)

juli95sosa@gmail.com

 

ACTIVE GRANTS

Research:

-International Brain Research Organization – Early Career Award (2019-2020)

-Agencia Nacional de Promoción Científica y Tecnológica: PICT-2016-0838 y PICT-2018-00684.

Outreach:

– International Brain Research Organization/DANA Foundation – Brain Awareness Week 2020.

– Sociedad Argentina de Investigación en Neurociencias – Semana del Cerebro 2020.

 

PUBLICATIONS (LAST 5 YEARS

  • 2020 Martínez GF, Gazal NG, Quassollo G, Szalai AM, Cid-Pellitero ED, Durcan TM, Fon EA, Bisbal M, Stefani FD, Unsain N. Quantitative expansion microscopy for the characterization of the spectrin periodic skeleton of axons using fluorescence microscopy. Sci Rep. 2020 Feb 19;10(1):2917. doi: 10.1038/s41598-020-59856-w.

  • 2020 Girouard MP, Simas T, Hua L, Morquette B, Khazaei MR, Unsain N, Johnstone AD, Rambaldi I, Sanz RL, Di Raddo ME, Gamage KK, Yong Y, Willis DE, Verge VMK, Barker PA, Deppmann C, Fournier AE. Collapsin Response Mediator Protein 4 (CRMP4) Facilitates Wallerian Degeneration and Axon Regeneration following Sciatic Nerve Injury. eNeuro. 2020 Mar 2;7(2). pii: ENEURO.0479-19.2020. doi: 10.1523/ENEURO.0479-19.2020.
  • 2019 Johnstone AD, de Léon A, Unsain N, Gibon J, Barker PA. Developmental Axon Degeneration Requires TRPV1-Dependent Ca2+ Influx. eNeuro. 2019 Feb 27;6(1). pii: ENEURO.0019-19.2019. doi: 10.1523/ENEURO.0019-19.2019. eCollection 2019 Jan-Feb.

  • 2018 Unsain N, Stefani FD, Cáceres A.The Actin/Spectrin Membrane-Associated Periodic Skeleton in Neurons. Front Synaptic Neurosci. 2018 May 23; 10:10. doi: 10.3389/fnsyn.2018.00010. Review.

  • 2018 Unsain N, Bordenave MD, Martinez GF, Jalil S, von Bilderling C, Barabas FM, Masullo LA, Johnstone AD, Barker PA, Bisbal M, Stefani FD, Cáceres AO. Remodeling of the Actin/Spectrin Membrane-associated Periodic Skeleton, Growth Cone Collapse and F-Actin Decrease during Axonal Degeneration. Sci Rep. 2018 Apr 12;8(1):6002. doi: 10.1038/s41598-018-23781-w.

  • 2017 Barabas FM, Masullo LA, Bordenave MD, A Giusti S, Unsain N, Refojo D, Cáceres A, Stefani FD. Automated quantification of protein periodic nanostructures in fluorescence nanoscopy images: abundance and regularity of neuronal spectrin membrane-associated skeleton. Sci Rep. 2017 Nov 22;7(1):16029. doi: 10.1038/s41598-017-16280-x.

  • 2017 Zanin JP, Unsain N, Anastasia A. Growth factors and hormones pro-peptides: the unexpected adventures of the BDNF prodomain. J Neurochem. 2017 Feb 20. doi: 10.1111/jnc.13993.

  • 2016 Unsain N, Dorval G, Sheen JH, Barker PA. Generation and characterization of mice bearing null alleles of nradd/Nrh2. Genesis. 2016 Oct 24. doi: 10.1002/dvg.22989.

  • 2016 Danelon V, Montroull LE, Unsain N, Barker PA, Mascó DH. Calpain-dependent truncated form of TrkB-FL increases in neurodegenerative processes. Mol Cell Neurosci. 2016 Sep;75:81-92.

  • 2016 Gibon J, Unsain N, Gamache K, Thomas RA, De Leon A, Johnstone A, Nader K, Séguéla P, Barker PA. The X-linked inhibitor of apoptosis regulates long-term depression and learning rate. FASEB J. 2016 Sep;30(9):3083-90.

  • 2015 Unsain N, Barker PA. New Views on the Misconstrued: Executioner Caspases and Their Diverse Non-apoptotic Roles. Neuron. 2015 Nov 4;88(3):461-74. doi: 10.1016/j.neuron.2015.08.029. Review.

  • 2015 Cueva Vargas JL, Osswald IK, Unsain N, Aurousseau MR, Barker PA, Bowie D, Di Polo A. Soluble Tumor Necrosis Factor Alpha Promotes Retinal Ganglion Cell Death in Glaucoma via Calcium-Permeable AMPA Receptor Activation. J Neurosci. 2015 Sep 2;35(35):12088-102. doi: 10.1523/JNEUROSCI.1273-15.2015.

  • 2015 Gibon J, Buckley SM*, Unsain N*, Kaartinen V, Séguéla P, Barker PA. proBDNF and p75NTR Control Excitability and Persistent Firing of Cortical Pyramidal Neurons. J Neurosci. 2015 Jul 1;35(26):9741-53. doi: 10.1523/JNEUROSCI.4655-14.2015. *“Equal contribution”.

 

SELECTED PUBLICATIONS

  • 2020 Martínez GF, Gazal NG, Quassollo G, Szalai AM, Cid-Pellitero ED, Durcan TM, Fon EA, Bisbal M, Stefani FD, Unsain N. Quantitative expansion microscopy for the characterization of the spectrin periodic skeleton of axons using fluorescence microscopy. Sci Rep. 2020 Feb 19;10(1):2917.

  • 2018 Unsain N, Stefani FD, Cáceres A.The Actin/Spectrin Membrane-Associated Periodic Skeleton in Neurons. Front Synaptic Neurosci. 2018 May 23; 10:10.  Review.

  • 2018 Unsain N, Bordenave MD, Martinez GF, Jalil S, von Bilderling C, Barabas FM, Masullo LA, Johnstone AD, Barker PA, Bisbal M, Stefani FD, Cáceres AO. Remodeling of the Actin/Spectrin Membrane-associated Periodic Skeleton, Growth Cone Collapse and F-Actin Decrease during Axonal Degeneration. Sci Rep. 2018 Apr 12;8(1):6002.

  • 2015 Unsain N, Barker PA. New Views on the Misconstrued: Executioner Caspases and Their Diverse Non-apoptotic Roles. Neuron. 2015 Nov 4;88(3):461-74. Review.

  • 2013 Unsain N, Higgins JM, Parker KN, Johnstone AD and Barker PA. XIAP regulates caspase activity in degenerating axons. Cell Reports. 2013 Aug 29;4(4):751-63

 

CONTACT

Dr. Nicolás Unsain

Phone: 54-351-468-1465, Int. 137

e-mail: nunsain@immf.uncor.edu

Google Scholar profile: http://scholar.google.ca/citations?user=YJ7VS1YAAAAJ&hl=en