![Cezar Tigaret](https://profiles-cardiff.imgix.net/attachments/3667?w=200&h=200&auto=format&crop=faces&fit=crop&q=90")
Dr Cezar Tigaret
(Translated he/him)
Hodge Lecturer in Neuroscience, Neuroscience and Mental Health Innovation Institute
- Ar gael fel goruchwyliwr ôl-raddedig
Trosolwyg
Fy nod yw deall y achosoldeb rhwng ffactorau risg seiciatrig ac ymddangosiad symptomau a diffygion gwybyddol mewn salwch seiciatrig, wedi'u hategu gan newidiadau mewn swyddogaethau synaptig a chylchedau niwral.
Mae astudiaethau diweddar wedi canfod risg genetig gymhleth mewn salwch seiciatrig fel sgitsoffrenia ac anhwylder deubegynol. Mae'r darganfyddiadau hyn yn awgrymu newidiadau yn swyddogaeth celloedd yr ymennydd a sut maent yn cyfathrebu â'i gilydd, yn y symptomau cyffredin a geir mewn seicosis. Erbyn hyn mae angen brys i drosi'r darganfyddiadau hyn yn therapïau mwy effeithiol yn seiliedig ar achosiad.
Mae gen i ddiddordeb arbennig mewn plastigrwydd synaptig fel prif fecanwaith cellog o ddysgu cysylltiol sy'n sail i'n rhesymu a'n gallu i gynrychioli ac addasu i'r amgylchedd ac sy'n cael ei amharu mewn seicosis.
Rwy'n cyfuno delweddu dwy ffoton o'r radd flaenaf ac electroffisioleg sleisio sleisio ex vivo mewn modelau anifeiliaid ac mewn technegau modelu seilos .
Cyhoeddiad
2023
- Indrigo, M. et al. 2023. Nuclear ERK1/2 signaling potentiation enhances neuroprotection and cognition via Importinα1/KPNA2. EMBO Molecular Medicine 15(11), article number: e15984. (10.15252/emmm.202215984)
- Rodrigues, Y. E., Tigaret, C. M., Marie, H., O'Donnell, C. and Veltz, R. 2023. A stochastic model of hippocampal synaptic plasticity with geometrical readout of enzyme dynamics. eLife 12, article number: e80152. (10.7554/eLife.80152)
2021
- Tigaret, C. M. et al. 2021. Neurotrophin receptor activation rescues cognitive and synaptic abnormalities caused by hemizygosity of the psychiatric risk gene Cacna1c. Molecular Psychiatry 26, pp. 1748-1760. (10.1038/s41380-020-01001-0)
2018
- Tigaret, C. M., Chamberlain, S. E. L., Sadowski, J. H. L. P., Hall, J., Ashby, M. C. and Mellor, J. R. 2018. Convergent metabotropic signalling pathways inhibit SK channels to promote synaptic plasticity in the hippocampus. Journal of Neuroscience 38(43), pp. 9252-9262. (10.1523/JNEUROSCI.1160-18.2018)
2016
- Prince, L. Y., Bacon, T. J., Tigaret, C. M. and Mellor, J. R. 2016. Neuromodulation of the feedforward dentate gyrus-CA3 microcircuit. Frontiers in Synaptic Neuroscience 8, article number: 32. (10.3389/fnsyn.2016.00032)
- Tigaret, C. M., Olivo, V., Sadowski, J. H. L. P., Ashby, M. C. and Mellor, J. R. 2016. Coordinated activation of distinct Ca2+ sources and metabotropic glutamate receptors encodes Hebbian synaptic plasticity. Nature Communications 7(1), article number: 10289. (10.1038/ncomms10289)
2015
- Glebov, O. O., Tigaret, C. M., Mellor, J. R. and Henley, J. M. 2015. Clathrin-independent trafficking of AMPA receptors. Journal of Neuroscience 35(12), pp. 4830-4836. (10.1523/JNEUROSCI.3571-14.2015)
2013
- Tigaret, C. M., Tsaneva-Atanasova, K., Collingridge, G. L. and Mellor, J. R. 2013. Wavelet Transform-Based De-Noising for Two-Photon Imaging of Synaptic Ca 2+ Transients. Biophysical Journal 104(5), pp. 1006-1017. (10.1016/j.bpj.2013.01.015)
2011
- Sainlos, M. et al. 2011. Biomimetic divalent ligands for the acute disruption of synaptic AMPAR stabilization. Nature Chemical Biology 7(2), pp. 81-91. (10.1038/nchembio.498)
2010
- Opazo, P., Labrecque, S., Tigaret, C. M., Frouin, A., Wiseman, P. W., De Koninck, P. and Choquet, D. 2010. CaMKII Triggers the Diffusional Trapping of Surface AMPARs through Phosphorylation of Stargazin. Neuron 67(2), pp. 239-252. (10.1016/j.neuron.2010.06.007)
2009
- Chen, P. E. et al. 2009. Behavioral deficits and subregion-specific suppression of LTP in mice expressing a population of mutant NMDA receptors throughout the hippocampus. Learning and Memory 16(10), pp. 635-644. (10.1101/lm.1316909)
- Tigaret, C. and Choquet, D. 2009. More AMPAR Garnish. Science 323(5919), pp. 1295-1296. (10.1126/science.1171519)
2008
- Medvedev, N. I., Rodríguez-Arellano, J. J., Popov, V. I., Davies, H. A., Tigaret, C. M., Schoepfer, R. and Stewart, M. G. 2008. The glutamate receptor?2 subunit controls post-synaptic density complexity and spine shape in the dentate gyrus. European Journal of Neuroscience 27(2), pp. 315-325. (10.1111/j.1460-9568.2007.06005.x)
2006
- Thalhammer, A., Rudhard, Y., Tigaret, C. M., Volynski, K. E., Rusakov, D. A. and Schoepfer, R. 2006. CaMKII translocation requires local NMDA receptor-mediated Ca2+ signaling. EMBO Journal 25(24), pp. 5873-5883. (10.1038/sj.emboj.7601420)
- Tigaret, C. M., Thalhammer, A., Rast, G. F., Specht, C. G., Auberson, Y. P., Stewart, M. G. and Schoepfer, R. 2006. Subunit Dependencies of N-Methyl-d-aspartate (NMDA) Receptor-Induced ?-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Internalization. Molecular Pharmacology 69(4), pp. 1251-1259. (10.1124/mol.105.018580)
2005
- Specht, C. G., Tigaret, C. M., Rast, G. F., Thalhammer, A., Rudhard, Y. and Schoepfer, R. 2005. Subcellular localisation of recombinant α- and γ-synuclein. Molecular and Cellular Neuroscience 28(2), pp. 326-334. (10.1016/j.mcn.2004.09.017)
2003
- Rudhard, Y. et al. 2003. Absence of Whisker-Related Pattern Formation in Mice with NMDA Receptors Lacking Coincidence Detection Properties and Calcium Signaling. Journal of Neuroscience 23(6), pp. 2323-2332. (10.1523/JNEUROSCI.23-06-02323.2003)
1994
- Popescu, L. M. et al. 1994. K(+)-channel openers protect the myocardium against ischemia-reperfusion injury. Annals of the New York Academy of Sciences 723(1), pp. 398-400. (10.1111/j.1749-6632.1994.tb36757.x)
1992
- Prasad, M. R., Tigaret, C. M., Smith, D., Soares, H. and McIntosh, T. K. 1992. Decreased α1-adrenergic receptors after experimental brain injury. Journal of Neurotrauma 9(3), pp. 269-279. (10.1089/neu.1992.9.269)
1988
- Popescu, L. M., Hinescu, M. E., Constantinescu, S., Tigaret, C. M., Cinteză, M. and Gherasim, L. 1988. Molecular mechanism of tolerance for vasodilator nitrates. Revista de medicină internă, neurologe, psihiatrie, neurochirurgie, dermato-venerologie. Medicină internă 40, pp. 145-154.
Articles
- Indrigo, M. et al. 2023. Nuclear ERK1/2 signaling potentiation enhances neuroprotection and cognition via Importinα1/KPNA2. EMBO Molecular Medicine 15(11), article number: e15984. (10.15252/emmm.202215984)
- Rodrigues, Y. E., Tigaret, C. M., Marie, H., O'Donnell, C. and Veltz, R. 2023. A stochastic model of hippocampal synaptic plasticity with geometrical readout of enzyme dynamics. eLife 12, article number: e80152. (10.7554/eLife.80152)
- Tigaret, C. M. et al. 2021. Neurotrophin receptor activation rescues cognitive and synaptic abnormalities caused by hemizygosity of the psychiatric risk gene Cacna1c. Molecular Psychiatry 26, pp. 1748-1760. (10.1038/s41380-020-01001-0)
- Tigaret, C. M., Chamberlain, S. E. L., Sadowski, J. H. L. P., Hall, J., Ashby, M. C. and Mellor, J. R. 2018. Convergent metabotropic signalling pathways inhibit SK channels to promote synaptic plasticity in the hippocampus. Journal of Neuroscience 38(43), pp. 9252-9262. (10.1523/JNEUROSCI.1160-18.2018)
- Prince, L. Y., Bacon, T. J., Tigaret, C. M. and Mellor, J. R. 2016. Neuromodulation of the feedforward dentate gyrus-CA3 microcircuit. Frontiers in Synaptic Neuroscience 8, article number: 32. (10.3389/fnsyn.2016.00032)
- Tigaret, C. M., Olivo, V., Sadowski, J. H. L. P., Ashby, M. C. and Mellor, J. R. 2016. Coordinated activation of distinct Ca2+ sources and metabotropic glutamate receptors encodes Hebbian synaptic plasticity. Nature Communications 7(1), article number: 10289. (10.1038/ncomms10289)
- Glebov, O. O., Tigaret, C. M., Mellor, J. R. and Henley, J. M. 2015. Clathrin-independent trafficking of AMPA receptors. Journal of Neuroscience 35(12), pp. 4830-4836. (10.1523/JNEUROSCI.3571-14.2015)
- Tigaret, C. M., Tsaneva-Atanasova, K., Collingridge, G. L. and Mellor, J. R. 2013. Wavelet Transform-Based De-Noising for Two-Photon Imaging of Synaptic Ca 2+ Transients. Biophysical Journal 104(5), pp. 1006-1017. (10.1016/j.bpj.2013.01.015)
- Sainlos, M. et al. 2011. Biomimetic divalent ligands for the acute disruption of synaptic AMPAR stabilization. Nature Chemical Biology 7(2), pp. 81-91. (10.1038/nchembio.498)
- Opazo, P., Labrecque, S., Tigaret, C. M., Frouin, A., Wiseman, P. W., De Koninck, P. and Choquet, D. 2010. CaMKII Triggers the Diffusional Trapping of Surface AMPARs through Phosphorylation of Stargazin. Neuron 67(2), pp. 239-252. (10.1016/j.neuron.2010.06.007)
- Chen, P. E. et al. 2009. Behavioral deficits and subregion-specific suppression of LTP in mice expressing a population of mutant NMDA receptors throughout the hippocampus. Learning and Memory 16(10), pp. 635-644. (10.1101/lm.1316909)
- Tigaret, C. and Choquet, D. 2009. More AMPAR Garnish. Science 323(5919), pp. 1295-1296. (10.1126/science.1171519)
- Medvedev, N. I., Rodríguez-Arellano, J. J., Popov, V. I., Davies, H. A., Tigaret, C. M., Schoepfer, R. and Stewart, M. G. 2008. The glutamate receptor?2 subunit controls post-synaptic density complexity and spine shape in the dentate gyrus. European Journal of Neuroscience 27(2), pp. 315-325. (10.1111/j.1460-9568.2007.06005.x)
- Thalhammer, A., Rudhard, Y., Tigaret, C. M., Volynski, K. E., Rusakov, D. A. and Schoepfer, R. 2006. CaMKII translocation requires local NMDA receptor-mediated Ca2+ signaling. EMBO Journal 25(24), pp. 5873-5883. (10.1038/sj.emboj.7601420)
- Tigaret, C. M., Thalhammer, A., Rast, G. F., Specht, C. G., Auberson, Y. P., Stewart, M. G. and Schoepfer, R. 2006. Subunit Dependencies of N-Methyl-d-aspartate (NMDA) Receptor-Induced ?-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Internalization. Molecular Pharmacology 69(4), pp. 1251-1259. (10.1124/mol.105.018580)
- Specht, C. G., Tigaret, C. M., Rast, G. F., Thalhammer, A., Rudhard, Y. and Schoepfer, R. 2005. Subcellular localisation of recombinant α- and γ-synuclein. Molecular and Cellular Neuroscience 28(2), pp. 326-334. (10.1016/j.mcn.2004.09.017)
- Rudhard, Y. et al. 2003. Absence of Whisker-Related Pattern Formation in Mice with NMDA Receptors Lacking Coincidence Detection Properties and Calcium Signaling. Journal of Neuroscience 23(6), pp. 2323-2332. (10.1523/JNEUROSCI.23-06-02323.2003)
- Popescu, L. M. et al. 1994. K(+)-channel openers protect the myocardium against ischemia-reperfusion injury. Annals of the New York Academy of Sciences 723(1), pp. 398-400. (10.1111/j.1749-6632.1994.tb36757.x)
- Prasad, M. R., Tigaret, C. M., Smith, D., Soares, H. and McIntosh, T. K. 1992. Decreased α1-adrenergic receptors after experimental brain injury. Journal of Neurotrauma 9(3), pp. 269-279. (10.1089/neu.1992.9.269)
- Popescu, L. M., Hinescu, M. E., Constantinescu, S., Tigaret, C. M., Cinteză, M. and Gherasim, L. 1988. Molecular mechanism of tolerance for vasodilator nitrates. Revista de medicină internă, neurologe, psihiatrie, neurochirurgie, dermato-venerologie. Medicină internă 40, pp. 145-154.
Ymchwil
Canlyniadau synaptig a chylchedol amrywiad genetig mewn sianeli calsiwm wedi'i gratio foltedd.
Beth?
Mae sianeli calsiwm â gatiau foltage (VGCCs) yn broteinau sy'n trosi gweithgaredd trydanol niwronau yn signalau calsiwm cyflym sy'n goruchwylio dysgu a chof a rheoleiddio mynegiant genynnau yn yr ymennydd.
Pam?
Mae amrywiad genetig mewn is-unedau sianel calsiwm â gatiau foltedd, ac yn benodol, yn y genyn CACNA1C sy'n amgodio'r sianeli calsiwm wedi'i gratio foltedd CaV1.2 L-1.2 L-VGCCs yn cael ei gysylltu'n gryf â risg ar gyfer seicosis. Mae astudiaethau diweddar yn dangos bod y rhan fwyaf o amrywiadau sy'n gysylltiedig â risg o CACNA1C yn gweithredu i leihau lefelau CaV1.2 L-VGCCs yn yr ymennydd, ond mae'r cysylltiadau achosol â symptomau seiciatrig yn cael eu deall yn wael.
Sut?
Rwyf wedi datblygu fframwaith methodolegol i archwilio effaith synaptig, cylched, ac ymddygiad treigladau CACNA1C , mewn cydweithrediad â'r grwpiau dan arweiniad yr Athro Jeremy Hall a Dr. Kerrie Thomas yn NMHRI, a'r Athro Matt W. Jones (Prifysgol Bryste). Mae'r ymchwil yn cyd-fynd â'r thema ymchwil "Meddwl, yr ymennydd a niwrowyddoniaeth" yng Ngholeg y Gwyddorau Biofeddygol a Bywyd, ac mae'n integreiddio delweddu ac electroffisioleg dau lun o'r radd flaenaf gyda dadansoddiadau ymddygiadol.
Canlyniadau.
Yr astudiaeth, a gyhoeddwyd yn Seiciatreg Moleciwlaidd yn 2021, yw'r cyntaf i ddangos diffygion detholus llwybr mewn plastigrwydd synaptig Hebbeg a chydamseru cylched yn yr hippocampus, a dysgu cysylltiol sy'n dibynnu ar hippocampal wedi'i newid yn Cacna1c +/- anifeiliaid.
Mae'r astudiaeth hon hefyd yn dangos am y tro cyntaf achub ffenoteipiau niwrobiolegol ac ymddygiadol sy'n gysylltiedig â haploannigonolrwydd Cacna1c gan ddefnyddio cyffur â gweithgaredd mimetig BDNF niwrotroffig yn vivo.
Beth nesaf?
Yn 2021 dyfarnwyd Grant Ymchwil MRC 3 blynedd i mi fel unig PI, i holi potensial cyffuriau sianel Ca 2+ colenergic a Ca2+-sensitif K+ i achub canlyniadau dos CaV 1.2llai ar blastigrwydd synaptig ac integreiddio mewnbwn synaptig mewn niwronau.
Rwy'n cydweithio â'r Athro Frank Sengpiel (Ysgol y Biowyddorau) i ymchwilio i ganlyniadau synaptig mwtaniadau ennill swyddogaeth Cacna1c mewn modelau anifeiliaid syndrom Timothy.
Contact Details
Themâu ymchwil
Arbenigeddau
- Niwroseicoleg
- Niwrowyddoniaeth
- niwron
- Niwropharmacology
- swyddogaeth synaptig