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Scientific summary
Sensory neurons, Dorsal spinal cord interneurons, Schwann cells, Diabetic neuropathy
Diabetes mellitus (DM) is one of most common chronic diseases affecting mankind, having reached epidemic levels. One of the earliest and main complications in diabetic patients is diabetic peripheral neuropathy (DPN). DPN is a disorder of sensory nerves, and early in the course of DM, patients generally experience abnormal sensory symptoms such as pain, tingling, burning, stinging sensations (paresthesias), pain evoked by innocuous mechanical stimuli (allodynia) and increase sensitivity to noxious stimuli (hyperalgesia), as well as sensory deficits such as numbness. The progressive loss of lower extremity sensation often leads to tissue damage including severe deeply penetrating ulcers that increase the risk of amputation of the toe, foot, or leg. DM is the leading cause of lower extremity amputations, with a risk that is increased by 15-fold over the non-diabetic population. Most importantly, the pathology of DPN leads to substantial reduction in quality of life for the afflicted patients and cost for society. The enormity of this problem has now reached epidemic proportions. Despite decades of research, there are currently no effective therapies for DPN. This is due in large part to our incomplete understanding of the disease mechanisms that operate at the different levels of the somatosensory circuits.
The Atip-AVENIR team aims to better understand: 1) How DM affects primary sensory neurons subtypes and dorsal spinal cord circuits that process somatosensory information and how these neurons are involve during the course of the disease; 2) the role of lipid deregulation during the course of DPN.
We will use a combination of mouse genetic, confocal imaging, electrophysiological and behavioral approaches to better understand the disease mechanisms that operate at the different levels of the somatosensory circuits.
Diabetes mellitus (DM) is one of most common chronic diseases affecting mankind, having reached epidemic levels. One of the earliest and main complications in diabetic patients is diabetic peripheral neuropathy (DPN). DPN is a disorder of sensory nerves, and early in the course of DM, patients generally experience abnormal sensory symptoms such as pain, tingling, burning, stinging sensations (paresthesias), pain evoked by innocuous mechanical stimuli (allodynia) and increase sensitivity to noxious stimuli (hyperalgesia), as well as sensory deficits such as numbness. The progressive loss of lower extremity sensation often leads to tissue damage including severe deeply penetrating ulcers that increase the risk of amputation of the toe, foot, or leg. DM is the leading cause of lower extremity amputations, with a risk that is increased by 15-fold over the non-diabetic population. Most importantly, the pathology of DPN leads to substantial reduction in quality of life for the afflicted patients and cost for society. The enormity of this problem has now reached epidemic proportions. Despite decades of research, there are currently no effective therapies for DPN. This is due in large part to our incomplete understanding of the disease mechanisms that operate at the different levels of the somatosensory circuits.
The Atip-AVENIR team aims to better understand: 1) How DM affects primary sensory neurons subtypes and dorsal spinal cord circuits that process somatosensory information and how these neurons are involve during the course of the disease; 2) the role of lipid deregulation during the course of DPN.
We will use a combination of mouse genetic, confocal imaging, electrophysiological and behavioral approaches to better understand the disease mechanisms that operate at the different levels of the somatosensory circuits.
ANIMAL AND CELLULAR MODELS |
TECHNICS AND METHODS |
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Selected PUBLICATIONS
PCSK9 deficiency promotes the development of peripheral neuropathy
Ali K. Jaafar, Aurelie Paulo-Ramos, Guillaume Rastoldo, Bryan Veeren, Cynthia Planesse, Mattieu Bringart, Philippe Rondeau, Olivier Meilhac, Gilles Lambert, Steeve Bourane
bioRxiv 2024.03.03.583154; doi: https://doi.org/10.1101/2024.03.03.583154
Alteration of nociceptive Schwann cells in a mouse model of high-fat diet induced diabetic peripheral neuropathy
Guillaume Rastoldo, Ali K. Jaafar, Aurélie-Paulo-Ramos, Katy Thouvenot, Cynthia Planesse, Matthieu Bringart, Marie-Paule Gonthier, Gilles Lambert, Steeve Bourane
bioRxiv 2024.03.12.584541; doi: https://doi.org/10.1101/2024.03.12.584541
PCSK9 and the nervous system: a no-brainer?
Jaafar AK, Techer R, Chemello K, Lambert G, Bourane S.J Lipid Res. 2023 Sep;64(9):100426. doi: 10.1016/j.jlr.2023.100426. Epub 2023 Aug 14.PMID: 37586604 Free PMC article. Review.
Mafa-dependent GABAergic activity promotes mouse neonatal apneas.
Lecoin L, Dempsey B, Garancher A, Bourane S, Ruffault PL, Morin-Surun MP, Rocques N, Goulding M, Eychène A, Pouponnot C, Fortin G, Champagnat J.Nat Commun. 2022 Jun 7;13(1):3284. doi: 10.1038/s41467-022-30825-3.PMID: 35672398 Free PMC article.
Antioxidant Polyphenols of Antirhea borbonica Medicinal Plant and Caffeic Acid Reduce Cerebrovascular, Inflammatory and Metabolic Disorders Aggravated by High-Fat Diet-Induced Obesity in a Mouse Model of Stroke.
Taïlé J, Bringart M, Planesse C, Patché J, Rondeau P, Veeren B, Clerc P, Gauvin-Bialecki A, Bourane S, Meilhac O, Couret D, Gonthier MP.Antioxidants (Basel). 2022 Apr 27;11(5):858. doi: 10.3390/antiox11050858.PMID: 35624723 Free PMC article.
A Systematic Approach to Assess the Activity and Classification of PCSK9 Variants.
Uribe KB, Chemello K, Larrea-Sebal A, Benito-Vicente A, Galicia-Garcia U, Bourane S, Jaafar AK, Lambert G, Martín C.Int J Mol Sci. 2021 Dec 18;22(24):13602. doi: 10.3390/ijms222413602.PMID: 34948399 Free PMC article.
Lack of Neuroprotective Effects of High-Density Lipoprotein Therapy in Stroke under Acute Hyperglycemic Conditions.
Couret D, Planesse C, Patche J, Diotel N, Nativel B, Bourane S, Meilhac O.Molecules. 2021 Oct 21;26(21):6365. doi: 10.3390/molecules26216365.PMID: 34770774 Free PMC article.
PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) Inhibition in Hyperglycemic Mice Increases the Risk of Hemorrhagic Transformation of Ischemic Stroke.
Nativel B, Ramin-Mangata S, Couret D, Planesse C, Roche M, Gallo A, Meilhac O, Lambert G, Bourane S.Stroke. 2021 Aug;52(9):e545-e547. doi: 10.1161/STROKEAHA.121.035677. Epub 2021 Jul 28.PMID: 34315254
A Functional Topographic Map for Spinal Sensorimotor Reflexes.
Gatto G, Bourane S, Ren X, Di Costanzo S, Fenton PK, Halder P, Seal RP, Goulding MD.Neuron. 2021 Jan 6;109(1):91-104.e5. doi: 10.1016/j.neuron.2020.10.003. Epub 2020 Nov 11.PMID: 33181065 Free PMC article.
Homozygous Familial Hypercholesterolemia Patients With Identical Mutations Variably Express the LDLR (Low-Density Lipoprotein Receptor): Implications for the Efficacy of Evolocumab.
Thedrez A, Blom DJ, Ramin-Mangata S, Blanchard V, Croyal M, Chemello K, Nativel B, Pichelin M, Cariou B, Bourane S, Tang L, Farnier M, Raal FJ, Lambert G.Arterioscler Thromb Vasc Biol. 2018 Mar;38(3):592-598. doi: 10.1161/ATVBAHA.117.310217. Epub 2017 Dec 28.PMID: 29284604 Free PMC article. Clinical Trial.
A hemorrhagic transformation model of mechanical stroke therapy with acute hyperglycemia in mice.
Couret D, Bourane S, Catan A, Nativel B, Planesse C, Dorsemans AC, Ait-Arsa I, Cournot M, Rondeau P, Patche J, Tran-Dinh A, Lambert G, Diotel N, Meilhac O.J Comp Neurol. 2018 Apr 15;526(6):1006-1016. doi: 10.1002/cne.24386. Epub 2018 Jan 7.PMID: 29277912
[A subpopulation of interneurons in the dorsal spinal cord involved in mechanical itch].
Bourane S.Med Sci (Paris). 2016 Jun-Jul;32(6-7):547-50. doi: 10.1051/medsci/20163206006. Epub 2016 Jul 12.PMID: 27406753 Free article. French. No abstract available.
Gate control of mechanical itch by a subpopulation of spinal cord interneurons.
Bourane S, Duan B, Koch SC, Dalet A, Britz O, Garcia-Campmany L, Kim E, Cheng L, Ghosh A, Ma Q, Goulding M.Science. 2015 Oct 30;350(6260):550-4. doi: 10.1126/science.aac8653.PMID: 26516282 Free PMC article.
Identification of a spinal circuit for light touch and fine motor control.
Bourane S, Grossmann KS, Britz O, Dalet A, Del Barrio MG, Stam FJ, Garcia-Campmany L, Koch S, Goulding M.Cell. 2015 Jan 29;160(3):503-15. doi: 10.1016/j.cell.2015.01.011.PMID: 25635458 Free PMC article.
Identification of spinal circuits transmitting and gating mechanical pain.
Duan B, Cheng L, Bourane S, Britz O, Padilla C, Garcia-Campmany L, Krashes M, Knowlton W, Velasquez T, Ren X, Ross S, Lowell BB, Wang Y, Goulding M, Ma Q.Cell. 2014 Dec 4;159(6):1417-1432. doi: 10.1016/j.cell.2014.11.003. Epub 2014 Nov 20.PMID: 25467445 Free PMC article.
CaMKK-CaMK1a, a new post-traumatic signalling pathway induced in mouse somatosensory neurons.
Elzière L, Sar C, Ventéo S, Bourane S, Puech S, Sonrier C, Boukhadaoui H, Fichard A, Pattyn A, Valmier J, Carroll P, Méchaly I.PLoS One. 2014 May 19;9(5):e97736. doi: 10.1371/journal.pone.0097736. eCollection 2014.PMID: 24840036 Free PMC article.
Inhibition downunder: an update from the spinal cord.
Goulding M, Bourane S, Garcia-Campmany L, Dalet A, Koch S.Curr Opin Neurobiol. 2014 Jun;26:161-6. doi: 10.1016/j.conb.2014.03.006. Epub 2014 Apr 17.PMID: 24743058 Free PMC article. Review.
A transcription factor code defines nine sensory interneuron subtypes in the mechanosensory area of the spinal cord.
Del Barrio MG, Bourane S, Grossmann K, Schüle R, Britsch S, O'Leary DD, Goulding M.PLoS One. 2013 Nov 4;8(11):e77928. doi: 10.1371/journal.pone.0077928. eCollection 2013.PMID: 24223744 Free PMC article.
The transcription factor c-Maf controls touch receptor development and function.
Wende H, Lechner SG, Cheret C, Bourane S, Kolanczyk ME, Pattyn A, Reuter K, Munier FL, Carroll P, Lewin GR, Birchmeier C.Science. 2012 Mar 16;335(6074):1373-6. doi: 10.1126/science.1214314. Epub 2012 Feb 16.PMID: 22345400
Regulation of the Na,K-ATPase gamma-subunit FXYD2 by Runx1 and Ret signaling in normal and injured non-peptidergic nociceptive sensory neurons.
Ventéo S, Bourane S, Méchaly I, Sar C, Abdel Samad O, Puech S, Blostein R, Valmier J, Pattyn A, Carroll P.PLoS One. 2012;7(1):e29852. doi: 10.1371/journal.pone.0029852. Epub 2012 Jan 13.PMID: 22253804 Free PMC article.
Low-threshold mechanoreceptor subtypes selectively express MafA and are specified by Ret signaling.
Bourane S, Garces A, Venteo S, Pattyn A, Hubert T, Fichard A, Puech S, Boukhaddaoui H, Baudet C, Takahashi S, Valmier J, Carroll P.Neuron. 2009 Dec 24;64(6):857-70. doi: 10.1016/j.neuron.2009.12.004.PMID: 20064392 Free article.
Ali K. Jaafar, Aurelie Paulo-Ramos, Guillaume Rastoldo, Bryan Veeren, Cynthia Planesse, Mattieu Bringart, Philippe Rondeau, Olivier Meilhac, Gilles Lambert, Steeve Bourane
bioRxiv 2024.03.03.583154; doi: https://doi.org/10.1101/2024.03.03.583154
Alteration of nociceptive Schwann cells in a mouse model of high-fat diet induced diabetic peripheral neuropathy
Guillaume Rastoldo, Ali K. Jaafar, Aurélie-Paulo-Ramos, Katy Thouvenot, Cynthia Planesse, Matthieu Bringart, Marie-Paule Gonthier, Gilles Lambert, Steeve Bourane
bioRxiv 2024.03.12.584541; doi: https://doi.org/10.1101/2024.03.12.584541
PCSK9 and the nervous system: a no-brainer?
Jaafar AK, Techer R, Chemello K, Lambert G, Bourane S.J Lipid Res. 2023 Sep;64(9):100426. doi: 10.1016/j.jlr.2023.100426. Epub 2023 Aug 14.PMID: 37586604 Free PMC article. Review.
Mafa-dependent GABAergic activity promotes mouse neonatal apneas.
Lecoin L, Dempsey B, Garancher A, Bourane S, Ruffault PL, Morin-Surun MP, Rocques N, Goulding M, Eychène A, Pouponnot C, Fortin G, Champagnat J.Nat Commun. 2022 Jun 7;13(1):3284. doi: 10.1038/s41467-022-30825-3.PMID: 35672398 Free PMC article.
Antioxidant Polyphenols of Antirhea borbonica Medicinal Plant and Caffeic Acid Reduce Cerebrovascular, Inflammatory and Metabolic Disorders Aggravated by High-Fat Diet-Induced Obesity in a Mouse Model of Stroke.
Taïlé J, Bringart M, Planesse C, Patché J, Rondeau P, Veeren B, Clerc P, Gauvin-Bialecki A, Bourane S, Meilhac O, Couret D, Gonthier MP.Antioxidants (Basel). 2022 Apr 27;11(5):858. doi: 10.3390/antiox11050858.PMID: 35624723 Free PMC article.
A Systematic Approach to Assess the Activity and Classification of PCSK9 Variants.
Uribe KB, Chemello K, Larrea-Sebal A, Benito-Vicente A, Galicia-Garcia U, Bourane S, Jaafar AK, Lambert G, Martín C.Int J Mol Sci. 2021 Dec 18;22(24):13602. doi: 10.3390/ijms222413602.PMID: 34948399 Free PMC article.
Lack of Neuroprotective Effects of High-Density Lipoprotein Therapy in Stroke under Acute Hyperglycemic Conditions.
Couret D, Planesse C, Patche J, Diotel N, Nativel B, Bourane S, Meilhac O.Molecules. 2021 Oct 21;26(21):6365. doi: 10.3390/molecules26216365.PMID: 34770774 Free PMC article.
PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) Inhibition in Hyperglycemic Mice Increases the Risk of Hemorrhagic Transformation of Ischemic Stroke.
Nativel B, Ramin-Mangata S, Couret D, Planesse C, Roche M, Gallo A, Meilhac O, Lambert G, Bourane S.Stroke. 2021 Aug;52(9):e545-e547. doi: 10.1161/STROKEAHA.121.035677. Epub 2021 Jul 28.PMID: 34315254
A Functional Topographic Map for Spinal Sensorimotor Reflexes.
Gatto G, Bourane S, Ren X, Di Costanzo S, Fenton PK, Halder P, Seal RP, Goulding MD.Neuron. 2021 Jan 6;109(1):91-104.e5. doi: 10.1016/j.neuron.2020.10.003. Epub 2020 Nov 11.PMID: 33181065 Free PMC article.
Homozygous Familial Hypercholesterolemia Patients With Identical Mutations Variably Express the LDLR (Low-Density Lipoprotein Receptor): Implications for the Efficacy of Evolocumab.
Thedrez A, Blom DJ, Ramin-Mangata S, Blanchard V, Croyal M, Chemello K, Nativel B, Pichelin M, Cariou B, Bourane S, Tang L, Farnier M, Raal FJ, Lambert G.Arterioscler Thromb Vasc Biol. 2018 Mar;38(3):592-598. doi: 10.1161/ATVBAHA.117.310217. Epub 2017 Dec 28.PMID: 29284604 Free PMC article. Clinical Trial.
A hemorrhagic transformation model of mechanical stroke therapy with acute hyperglycemia in mice.
Couret D, Bourane S, Catan A, Nativel B, Planesse C, Dorsemans AC, Ait-Arsa I, Cournot M, Rondeau P, Patche J, Tran-Dinh A, Lambert G, Diotel N, Meilhac O.J Comp Neurol. 2018 Apr 15;526(6):1006-1016. doi: 10.1002/cne.24386. Epub 2018 Jan 7.PMID: 29277912
[A subpopulation of interneurons in the dorsal spinal cord involved in mechanical itch].
Bourane S.Med Sci (Paris). 2016 Jun-Jul;32(6-7):547-50. doi: 10.1051/medsci/20163206006. Epub 2016 Jul 12.PMID: 27406753 Free article. French. No abstract available.
Gate control of mechanical itch by a subpopulation of spinal cord interneurons.
Bourane S, Duan B, Koch SC, Dalet A, Britz O, Garcia-Campmany L, Kim E, Cheng L, Ghosh A, Ma Q, Goulding M.Science. 2015 Oct 30;350(6260):550-4. doi: 10.1126/science.aac8653.PMID: 26516282 Free PMC article.
Identification of a spinal circuit for light touch and fine motor control.
Bourane S, Grossmann KS, Britz O, Dalet A, Del Barrio MG, Stam FJ, Garcia-Campmany L, Koch S, Goulding M.Cell. 2015 Jan 29;160(3):503-15. doi: 10.1016/j.cell.2015.01.011.PMID: 25635458 Free PMC article.
Identification of spinal circuits transmitting and gating mechanical pain.
Duan B, Cheng L, Bourane S, Britz O, Padilla C, Garcia-Campmany L, Krashes M, Knowlton W, Velasquez T, Ren X, Ross S, Lowell BB, Wang Y, Goulding M, Ma Q.Cell. 2014 Dec 4;159(6):1417-1432. doi: 10.1016/j.cell.2014.11.003. Epub 2014 Nov 20.PMID: 25467445 Free PMC article.
CaMKK-CaMK1a, a new post-traumatic signalling pathway induced in mouse somatosensory neurons.
Elzière L, Sar C, Ventéo S, Bourane S, Puech S, Sonrier C, Boukhadaoui H, Fichard A, Pattyn A, Valmier J, Carroll P, Méchaly I.PLoS One. 2014 May 19;9(5):e97736. doi: 10.1371/journal.pone.0097736. eCollection 2014.PMID: 24840036 Free PMC article.
Inhibition downunder: an update from the spinal cord.
Goulding M, Bourane S, Garcia-Campmany L, Dalet A, Koch S.Curr Opin Neurobiol. 2014 Jun;26:161-6. doi: 10.1016/j.conb.2014.03.006. Epub 2014 Apr 17.PMID: 24743058 Free PMC article. Review.
A transcription factor code defines nine sensory interneuron subtypes in the mechanosensory area of the spinal cord.
Del Barrio MG, Bourane S, Grossmann K, Schüle R, Britsch S, O'Leary DD, Goulding M.PLoS One. 2013 Nov 4;8(11):e77928. doi: 10.1371/journal.pone.0077928. eCollection 2013.PMID: 24223744 Free PMC article.
The transcription factor c-Maf controls touch receptor development and function.
Wende H, Lechner SG, Cheret C, Bourane S, Kolanczyk ME, Pattyn A, Reuter K, Munier FL, Carroll P, Lewin GR, Birchmeier C.Science. 2012 Mar 16;335(6074):1373-6. doi: 10.1126/science.1214314. Epub 2012 Feb 16.PMID: 22345400
Regulation of the Na,K-ATPase gamma-subunit FXYD2 by Runx1 and Ret signaling in normal and injured non-peptidergic nociceptive sensory neurons.
Ventéo S, Bourane S, Méchaly I, Sar C, Abdel Samad O, Puech S, Blostein R, Valmier J, Pattyn A, Carroll P.PLoS One. 2012;7(1):e29852. doi: 10.1371/journal.pone.0029852. Epub 2012 Jan 13.PMID: 22253804 Free PMC article.
Low-threshold mechanoreceptor subtypes selectively express MafA and are specified by Ret signaling.
Bourane S, Garces A, Venteo S, Pattyn A, Hubert T, Fichard A, Puech S, Boukhaddaoui H, Baudet C, Takahashi S, Valmier J, Carroll P.Neuron. 2009 Dec 24;64(6):857-70. doi: 10.1016/j.neuron.2009.12.004.PMID: 20064392 Free article.