In Vivo Ultrafast Doppler Imaging Combined with Confocal Microscopy and Behavioral Approaches to Gain Insight into the Central Expression of Peripheral Neuropathy in Trembler-J Mice
The main human hereditary peripheral neuropathy (Charcot-Marie-Tooth, CMT), manifests in progressive sensory and motor deficits. Mutations in the compact myelin protein gene pmp22 cause more than 50% of all CMTs. CMT1E is a subtype of CMT1 myelinopathy carrying micro-mutations in pmp22. The Trembler...
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2023-10-01
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| author | Mariana Martínez Barreiro Lucia Vázquez Alberdi Lucila De León Guadalupe Avellanal Andrea Duarte Maximiliano Anzibar Fialho Jérôme Baranger Miguel Calero Nicolás Rubido Mickael Tanter Carlos Negreira Javier Brum Juan Pablo Damián Alejandra Kun |
| author_facet | Mariana Martínez Barreiro Lucia Vázquez Alberdi Lucila De León Guadalupe Avellanal Andrea Duarte Maximiliano Anzibar Fialho Jérôme Baranger Miguel Calero Nicolás Rubido Mickael Tanter Carlos Negreira Javier Brum Juan Pablo Damián Alejandra Kun |
| author_sort | Mariana Martínez Barreiro |
| collection | DOAJ |
| description | The main human hereditary peripheral neuropathy (Charcot-Marie-Tooth, CMT), manifests in progressive sensory and motor deficits. Mutations in the compact myelin protein gene pmp22 cause more than 50% of all CMTs. CMT1E is a subtype of CMT1 myelinopathy carrying micro-mutations in pmp22. The Trembler-J mice have a spontaneous mutation in pmp22 identical to that present in CMT1E human patients. PMP22 is mainly (but not exclusively) expressed in Schwann cells. Some studies have found the presence of pmp22 together with some anomalies in the CNS of CMT patients. Recently, we identified the presence of higher hippocampal pmp22 expression and elevated levels of anxious behavior in TrJ/+ compared to those observed in wt. In the present paper, we delve deeper into the central expression of the neuropathy modeled in Trembler-J analyzing in vivo the cerebrovascular component by Ultrafast Doppler, exploring the vascular structure by scanning laser confocal microscopy, and analyzing the behavioral profile by anxiety and motor difficulty tests. We have found that TrJ/+ hippocampi have increased blood flow and a higher vessel volume compared with the wild type. Together with this, we found an anxiety-like profile in TrJ/+ and the motor difficulties described earlier. We demonstrate that there are specific cerebrovascular hemodynamics associated with a vascular structure and anxious behavior associated with the TrJ/+ clinical phenotype, a model of the human CMT1E disease. |
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| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T21:25:25Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-646ddf5f16ca456891999fd89466cc072023-11-19T15:43:42ZengMDPI AGBiology2079-77372023-10-011210132410.3390/biology12101324In Vivo Ultrafast Doppler Imaging Combined with Confocal Microscopy and Behavioral Approaches to Gain Insight into the Central Expression of Peripheral Neuropathy in Trembler-J MiceMariana Martínez Barreiro0Lucia Vázquez Alberdi1Lucila De León2Guadalupe Avellanal3Andrea Duarte4Maximiliano Anzibar Fialho5Jérôme Baranger6Miguel Calero7Nicolás Rubido8Mickael Tanter9Carlos Negreira10Javier Brum11Juan Pablo Damián12Alejandra Kun13Laboratorio de Biología Celular del Sistema Nervioso Periférico, Departamento de Proteínas y Ácidos Nucleicos, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, UruguayLaboratorio de Biología Celular del Sistema Nervioso Periférico, Departamento de Proteínas y Ácidos Nucleicos, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, UruguayDepartamento de Biociencias Veterinarias, Facultad de Veterinaria, Universidad de la República, Montevideo 13000, UruguayDepartamento de Biociencias Veterinarias, Facultad de Veterinaria, Universidad de la República, Montevideo 13000, UruguayLaboratorio de Biología Celular del Sistema Nervioso Periférico, Departamento de Proteínas y Ácidos Nucleicos, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, UruguayLaboratorio de Acústica Ultrasonora, Instituto de Física, Facultad de Ciencias, Universidad de la República, Montevideo 11400, UruguayPhysics for Medicine Paris, Inserm U1273, ESPCI Paris, PSL University, CNRS UMR 8063, 75012 Paris, FranceUnidad de Encefalopatías Espongiformes, UFIEC, CIBERNED, Instituto de Salud Carlos III, 28029 Madrid, SpainFísica No Lineal, Instituto de Física de Facultad de Ciencias, Universidad de la República, Montevideo 11400, UruguayPhysics for Medicine Paris, Inserm U1273, ESPCI Paris, PSL University, CNRS UMR 8063, 75012 Paris, FranceLaboratorio de Acústica Ultrasonora, Instituto de Física, Facultad de Ciencias, Universidad de la República, Montevideo 11400, UruguayLaboratorio de Acústica Ultrasonora, Instituto de Física, Facultad de Ciencias, Universidad de la República, Montevideo 11400, UruguayDepartamento de Biociencias Veterinarias, Facultad de Veterinaria, Universidad de la República, Montevideo 13000, UruguayLaboratorio de Biología Celular del Sistema Nervioso Periférico, Departamento de Proteínas y Ácidos Nucleicos, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, UruguayThe main human hereditary peripheral neuropathy (Charcot-Marie-Tooth, CMT), manifests in progressive sensory and motor deficits. Mutations in the compact myelin protein gene pmp22 cause more than 50% of all CMTs. CMT1E is a subtype of CMT1 myelinopathy carrying micro-mutations in pmp22. The Trembler-J mice have a spontaneous mutation in pmp22 identical to that present in CMT1E human patients. PMP22 is mainly (but not exclusively) expressed in Schwann cells. Some studies have found the presence of pmp22 together with some anomalies in the CNS of CMT patients. Recently, we identified the presence of higher hippocampal pmp22 expression and elevated levels of anxious behavior in TrJ/+ compared to those observed in wt. In the present paper, we delve deeper into the central expression of the neuropathy modeled in Trembler-J analyzing in vivo the cerebrovascular component by Ultrafast Doppler, exploring the vascular structure by scanning laser confocal microscopy, and analyzing the behavioral profile by anxiety and motor difficulty tests. We have found that TrJ/+ hippocampi have increased blood flow and a higher vessel volume compared with the wild type. Together with this, we found an anxiety-like profile in TrJ/+ and the motor difficulties described earlier. We demonstrate that there are specific cerebrovascular hemodynamics associated with a vascular structure and anxious behavior associated with the TrJ/+ clinical phenotype, a model of the human CMT1E disease.https://www.mdpi.com/2079-7737/12/10/1324Ultrafast Power DopplerScanning Laser Confocal Microscopybehavioral testsTrembler-JCMT1Eanxiety |
| spellingShingle | Mariana Martínez Barreiro Lucia Vázquez Alberdi Lucila De León Guadalupe Avellanal Andrea Duarte Maximiliano Anzibar Fialho Jérôme Baranger Miguel Calero Nicolás Rubido Mickael Tanter Carlos Negreira Javier Brum Juan Pablo Damián Alejandra Kun In Vivo Ultrafast Doppler Imaging Combined with Confocal Microscopy and Behavioral Approaches to Gain Insight into the Central Expression of Peripheral Neuropathy in Trembler-J Mice Biology Ultrafast Power Doppler Scanning Laser Confocal Microscopy behavioral tests Trembler-J CMT1E anxiety |
| title | In Vivo Ultrafast Doppler Imaging Combined with Confocal Microscopy and Behavioral Approaches to Gain Insight into the Central Expression of Peripheral Neuropathy in Trembler-J Mice |
| title_full | In Vivo Ultrafast Doppler Imaging Combined with Confocal Microscopy and Behavioral Approaches to Gain Insight into the Central Expression of Peripheral Neuropathy in Trembler-J Mice |
| title_fullStr | In Vivo Ultrafast Doppler Imaging Combined with Confocal Microscopy and Behavioral Approaches to Gain Insight into the Central Expression of Peripheral Neuropathy in Trembler-J Mice |
| title_full_unstemmed | In Vivo Ultrafast Doppler Imaging Combined with Confocal Microscopy and Behavioral Approaches to Gain Insight into the Central Expression of Peripheral Neuropathy in Trembler-J Mice |
| title_short | In Vivo Ultrafast Doppler Imaging Combined with Confocal Microscopy and Behavioral Approaches to Gain Insight into the Central Expression of Peripheral Neuropathy in Trembler-J Mice |
| title_sort | in vivo ultrafast doppler imaging combined with confocal microscopy and behavioral approaches to gain insight into the central expression of peripheral neuropathy in trembler j mice |
| topic | Ultrafast Power Doppler Scanning Laser Confocal Microscopy behavioral tests Trembler-J CMT1E anxiety |
| url | https://www.mdpi.com/2079-7737/12/10/1324 |
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