Central Alteration in Peripheral Neuropathy of Trembler-J Mice: Hippocampal pmp22 Expression and Behavioral Profile in Anxiety Tests
Charcot–Marie–Tooth (CMT) type 1 disease is the most common human hereditary demyelinating neuropathy. Mutations in pmp22 cause about 70% of all CMT1. Trembler-J (TrJ/+) mice are an animal model of CMT1E, having the same spontaneous pmp22 mutation that is found in humans. We compared the behavior pr...
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MDPI AG
2021-04-01
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| author | Juan Pablo Damián Lucia Vázquez Alberdi Lucía Canclini Gonzalo Rosso Silvia Olivera Bravo Mariana Martínez Natalia Uriarte Paul Ruiz Miguel Calero María Vittoria Di Tomaso Alejandra Kun |
| author_facet | Juan Pablo Damián Lucia Vázquez Alberdi Lucía Canclini Gonzalo Rosso Silvia Olivera Bravo Mariana Martínez Natalia Uriarte Paul Ruiz Miguel Calero María Vittoria Di Tomaso Alejandra Kun |
| author_sort | Juan Pablo Damián |
| collection | DOAJ |
| description | Charcot–Marie–Tooth (CMT) type 1 disease is the most common human hereditary demyelinating neuropathy. Mutations in pmp22 cause about 70% of all CMT1. Trembler-J (TrJ/+) mice are an animal model of CMT1E, having the same spontaneous pmp22 mutation that is found in humans. We compared the behavior profile of TrJ/+ and +/+ (wild-type) in open-field and elevated-plus-maze anxiety tests. In these tests, TrJ/+ showed an exclusive head shake movement, a lower frequency of rearing, but a greater frequency of grooming. In elevated-plus-maze, TrJ/+ defecate more frequently, performed fewer total entries, and have fewer entries to closed arms. These hippocampus-associated behaviors in TrJ/+ are consistent with increased anxiety levels. The expression of pmp22 and soluble PMP22 were evaluated in E17-hippocampal neurons and adult hippocampus by in situ hybridization and successive immunohistochemistry. Likewise, the expression of pmp22 was confirmed by RT-qPCR in the entire isolated hippocampi of both genotypes. Moreover, the presence of aggregated PMP22 was evidenced in unmasked granular hippocampal adult neurons and shows genotypic differences. We showed for the first time a behavior profile trait associated with anxiety and a differential expression of pmp22/PMP22 in hippocampal neurons of TrJ/+ and +/+ mice, demonstrating the involvement at the central level in an animal model of peripheral neuropathy (CMT1E). |
| first_indexed | 2024-03-10T12:11:22Z |
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| language | English |
| last_indexed | 2024-03-10T12:11:22Z |
| publishDate | 2021-04-01 |
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| series | Biomolecules |
| spelling | doaj.art-461983feae5e491e80584f460915064d2023-11-21T16:09:19ZengMDPI AGBiomolecules2218-273X2021-04-0111460110.3390/biom11040601Central Alteration in Peripheral Neuropathy of Trembler-J Mice: Hippocampal pmp22 Expression and Behavioral Profile in Anxiety TestsJuan Pablo Damián0Lucia Vázquez Alberdi1Lucía Canclini2Gonzalo Rosso3Silvia Olivera Bravo4Mariana Martínez5Natalia Uriarte6Paul Ruiz7Miguel Calero8María Vittoria Di Tomaso9Alejandra Kun10Unidad de Bioquímica, Departamento de Biociencias Veterinarias, Facultad de Veterinaria, Universidad de la República, 11600 Montevideo, UruguayDepartamento de Proteínas y Ácidos Nucleicos, Instituto de Investigaciones Biológicas Clemente Estable, 11600 Montevideo, UruguayDepartamento de Genética, Instituto de Investigaciones Biológicas Clemente Estable, 11600 Montevideo, UruguayMax Planck Institute for the Science of Light, Max-Planck-Zentrum für Physik und Medizin, 91058 Erlangen, GermanyNeurobiología Celular y Molecular, Instituto de Investigaciones Biológicas Clemente Estable, 11600 Montevideo, UruguayDepartamento de Proteínas y Ácidos Nucleicos, Instituto de Investigaciones Biológicas Clemente Estable, 11600 Montevideo, UruguayLaboratorio de Neurociencias, Facultad de Ciencias, Universidad de la República, 11400 Montevideo, UruguayUnidad de Biofísica, Departamento de Biociencias Veterinarias, Facultad de Veterinaria, Universidad de la República, 11600 Montevideo, UruguayUnidad de Encefalopatías Espongiformes, UFIEC, CIBERNED, CIEN Foundation, Queen Sofia Foundation Alzheimer Center, Instituto de Salud Carlos III, 28031 Madrid, SpainDepartamento de Genética, Instituto de Investigaciones Biológicas Clemente Estable, 11600 Montevideo, UruguayDepartamento de Proteínas y Ácidos Nucleicos, Instituto de Investigaciones Biológicas Clemente Estable, 11600 Montevideo, UruguayCharcot–Marie–Tooth (CMT) type 1 disease is the most common human hereditary demyelinating neuropathy. Mutations in pmp22 cause about 70% of all CMT1. Trembler-J (TrJ/+) mice are an animal model of CMT1E, having the same spontaneous pmp22 mutation that is found in humans. We compared the behavior profile of TrJ/+ and +/+ (wild-type) in open-field and elevated-plus-maze anxiety tests. In these tests, TrJ/+ showed an exclusive head shake movement, a lower frequency of rearing, but a greater frequency of grooming. In elevated-plus-maze, TrJ/+ defecate more frequently, performed fewer total entries, and have fewer entries to closed arms. These hippocampus-associated behaviors in TrJ/+ are consistent with increased anxiety levels. The expression of pmp22 and soluble PMP22 were evaluated in E17-hippocampal neurons and adult hippocampus by in situ hybridization and successive immunohistochemistry. Likewise, the expression of pmp22 was confirmed by RT-qPCR in the entire isolated hippocampi of both genotypes. Moreover, the presence of aggregated PMP22 was evidenced in unmasked granular hippocampal adult neurons and shows genotypic differences. We showed for the first time a behavior profile trait associated with anxiety and a differential expression of pmp22/PMP22 in hippocampal neurons of TrJ/+ and +/+ mice, demonstrating the involvement at the central level in an animal model of peripheral neuropathy (CMT1E).https://www.mdpi.com/2218-273X/11/4/601Charcot–Marie–Toothhippocampusperipheral-myelin-protein-22anxietyTrembler-JCA3 neurons |
| spellingShingle | Juan Pablo Damián Lucia Vázquez Alberdi Lucía Canclini Gonzalo Rosso Silvia Olivera Bravo Mariana Martínez Natalia Uriarte Paul Ruiz Miguel Calero María Vittoria Di Tomaso Alejandra Kun Central Alteration in Peripheral Neuropathy of Trembler-J Mice: Hippocampal pmp22 Expression and Behavioral Profile in Anxiety Tests Biomolecules Charcot–Marie–Tooth hippocampus peripheral-myelin-protein-22 anxiety Trembler-J CA3 neurons |
| title | Central Alteration in Peripheral Neuropathy of Trembler-J Mice: Hippocampal pmp22 Expression and Behavioral Profile in Anxiety Tests |
| title_full | Central Alteration in Peripheral Neuropathy of Trembler-J Mice: Hippocampal pmp22 Expression and Behavioral Profile in Anxiety Tests |
| title_fullStr | Central Alteration in Peripheral Neuropathy of Trembler-J Mice: Hippocampal pmp22 Expression and Behavioral Profile in Anxiety Tests |
| title_full_unstemmed | Central Alteration in Peripheral Neuropathy of Trembler-J Mice: Hippocampal pmp22 Expression and Behavioral Profile in Anxiety Tests |
| title_short | Central Alteration in Peripheral Neuropathy of Trembler-J Mice: Hippocampal pmp22 Expression and Behavioral Profile in Anxiety Tests |
| title_sort | central alteration in peripheral neuropathy of trembler j mice hippocampal pmp22 expression and behavioral profile in anxiety tests |
| topic | Charcot–Marie–Tooth hippocampus peripheral-myelin-protein-22 anxiety Trembler-J CA3 neurons |
| url | https://www.mdpi.com/2218-273X/11/4/601 |
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