Effects of the administration of Elovl5-dependent fatty acids on a spino-cerebellar ataxia 38 mouse model
Abstract Background Spinocerebellar ataxia 38 (SCA38) is a rare autosomal neurological disorder characterized by ataxia and cerebellar atrophy. SCA38 is caused by mutations of ELOVL5 gene. ELOVL5 gene encodes a protein, which elongates long chain polyunsaturated fatty acids (PUFAs). Knockout mice la...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Behavioral and Brain Functions |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12993-022-00194-4 |
| _version_ | 1811315293696294912 |
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| author | Ilaria Balbo Francesca Montarolo Federica Genovese Filippo Tempia Eriola Hoxha |
| author_facet | Ilaria Balbo Francesca Montarolo Federica Genovese Filippo Tempia Eriola Hoxha |
| author_sort | Ilaria Balbo |
| collection | DOAJ |
| description | Abstract Background Spinocerebellar ataxia 38 (SCA38) is a rare autosomal neurological disorder characterized by ataxia and cerebellar atrophy. SCA38 is caused by mutations of ELOVL5 gene. ELOVL5 gene encodes a protein, which elongates long chain polyunsaturated fatty acids (PUFAs). Knockout mice lacking Elovl5 recapitulate SCA38 symptoms, including motor coordination impairment and disruption of cerebellar architecture. We asked whether, in Elovl5 knockout mice (Elovl5 −/− ), a diet with both ω3 and ω6 PUFAs downstream Elovl5 can prevent the development of SCA38 symptoms, and at which age such treatment is more effective. Elovl5 −/− mice were fed either with a diet without or containing PUFAs downstream the Elovl5 enzyme, starting at different ages. Motor behavior was assessed by the balance beam test and cerebellar structure by morphometric analysis. Results The administration from birth of the diet containing PUFAs downstream Elovl5 led to a significant amelioration of the motor performance in the beam test of Elovl5 −/− mice, with a reduction of foot slip errors at 6 months from 2.2 ± 0.3 to 1.3 ± 0.2 and at 8 months from 3.1 ± 0.5 to 1.9 ± 0.3. On the contrary, administration at 1 month of age or later had no effect on the motor impairment. The cerebellar Purkinje cell layer and the white matter area of Elovl5 −/ − mice were not rescued even by the administration of diet from birth, suggesting that the improvement of motor performance in the beam test was due to a functional recovery of the cerebellar circuitry. Conclusions These results suggest that the dietary intervention in SCA38, whenever possible, should be started from birth or as early as possible. |
| first_indexed | 2024-04-13T11:28:56Z |
| format | Article |
| id | doaj.art-99278fc311464d4895dfbacab3f9fefa |
| institution | Directory Open Access Journal |
| issn | 1744-9081 |
| language | English |
| last_indexed | 2024-04-13T11:28:56Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Behavioral and Brain Functions |
| spelling | doaj.art-99278fc311464d4895dfbacab3f9fefa2022-12-22T02:48:38ZengBMCBehavioral and Brain Functions1744-90812022-08-0118111010.1186/s12993-022-00194-4Effects of the administration of Elovl5-dependent fatty acids on a spino-cerebellar ataxia 38 mouse modelIlaria Balbo0Francesca Montarolo1Federica Genovese2Filippo Tempia3Eriola Hoxha4Neuroscience Institute Cavalieri Ottolenghi (NICO)Neuroscience Institute Cavalieri Ottolenghi (NICO)Neuroscience Institute Cavalieri Ottolenghi (NICO)Neuroscience Institute Cavalieri Ottolenghi (NICO)Neuroscience Institute Cavalieri Ottolenghi (NICO)Abstract Background Spinocerebellar ataxia 38 (SCA38) is a rare autosomal neurological disorder characterized by ataxia and cerebellar atrophy. SCA38 is caused by mutations of ELOVL5 gene. ELOVL5 gene encodes a protein, which elongates long chain polyunsaturated fatty acids (PUFAs). Knockout mice lacking Elovl5 recapitulate SCA38 symptoms, including motor coordination impairment and disruption of cerebellar architecture. We asked whether, in Elovl5 knockout mice (Elovl5 −/− ), a diet with both ω3 and ω6 PUFAs downstream Elovl5 can prevent the development of SCA38 symptoms, and at which age such treatment is more effective. Elovl5 −/− mice were fed either with a diet without or containing PUFAs downstream the Elovl5 enzyme, starting at different ages. Motor behavior was assessed by the balance beam test and cerebellar structure by morphometric analysis. Results The administration from birth of the diet containing PUFAs downstream Elovl5 led to a significant amelioration of the motor performance in the beam test of Elovl5 −/− mice, with a reduction of foot slip errors at 6 months from 2.2 ± 0.3 to 1.3 ± 0.2 and at 8 months from 3.1 ± 0.5 to 1.9 ± 0.3. On the contrary, administration at 1 month of age or later had no effect on the motor impairment. The cerebellar Purkinje cell layer and the white matter area of Elovl5 −/ − mice were not rescued even by the administration of diet from birth, suggesting that the improvement of motor performance in the beam test was due to a functional recovery of the cerebellar circuitry. Conclusions These results suggest that the dietary intervention in SCA38, whenever possible, should be started from birth or as early as possible.https://doi.org/10.1186/s12993-022-00194-4Elovl5Spino-cerebellar ataxiaSCA38Motor deficitsPolyunsaturated fatty acids |
| spellingShingle | Ilaria Balbo Francesca Montarolo Federica Genovese Filippo Tempia Eriola Hoxha Effects of the administration of Elovl5-dependent fatty acids on a spino-cerebellar ataxia 38 mouse model Behavioral and Brain Functions Elovl5 Spino-cerebellar ataxia SCA38 Motor deficits Polyunsaturated fatty acids |
| title | Effects of the administration of Elovl5-dependent fatty acids on a spino-cerebellar ataxia 38 mouse model |
| title_full | Effects of the administration of Elovl5-dependent fatty acids on a spino-cerebellar ataxia 38 mouse model |
| title_fullStr | Effects of the administration of Elovl5-dependent fatty acids on a spino-cerebellar ataxia 38 mouse model |
| title_full_unstemmed | Effects of the administration of Elovl5-dependent fatty acids on a spino-cerebellar ataxia 38 mouse model |
| title_short | Effects of the administration of Elovl5-dependent fatty acids on a spino-cerebellar ataxia 38 mouse model |
| title_sort | effects of the administration of elovl5 dependent fatty acids on a spino cerebellar ataxia 38 mouse model |
| topic | Elovl5 Spino-cerebellar ataxia SCA38 Motor deficits Polyunsaturated fatty acids |
| url | https://doi.org/10.1186/s12993-022-00194-4 |
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