Cortical tau burden and behavioural dysfunctions in mice exposed to monosodium glutamate in early life.
Although monosodium glutamate (MSG)-induced neurotoxicity has been recognized for decades, the potential similarities of the MSG model to Alzheimer's disease (AD)-type neuropathology have only recently been investigated. MSG-treated mice were examined behaviourally and histologically in relatio...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0220720 |
| _version_ | 1818725609451290624 |
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| author | Passainte S Hassaan Abeer E Dief Teshreen M Zeitoun Azza M Baraka Robert M J Deacon Amany Elshorbagy |
| author_facet | Passainte S Hassaan Abeer E Dief Teshreen M Zeitoun Azza M Baraka Robert M J Deacon Amany Elshorbagy |
| author_sort | Passainte S Hassaan |
| collection | DOAJ |
| description | Although monosodium glutamate (MSG)-induced neurotoxicity has been recognized for decades, the potential similarities of the MSG model to Alzheimer's disease (AD)-type neuropathology have only recently been investigated. MSG-treated mice were examined behaviourally and histologically in relation to some features of AD. Four-week old mice received 5 subcutaneous MSG (2 g/kg) injections on alternate days, or saline. At age 10-12 weeks, they were given a battery of behavioural tests for species-typical behaviours and working memory. The mice were killed at 12 weeks and the brains excised. Accumulation of hyperphosphorylated tau protein was assessed in cortical and hippocampal neurons by immunohistochemistry, and in cerebral cortical homogenates. A 78% increase in cortical concentrations of phosphorylated tau protein was observed in the MSG mice. Intracellular hyperphosphorylated tau immunostaining was observed diffusely in the cortex and hippocampus, together with cortical atrophic neurons, extensive vacuolation and dysmorphic neuropil suggestive of spongiform neurodegeneration. Nest-building was significantly impaired, and spontaneous T-maze alternation was reduced, suggesting defective short-term working memory. Subcutaneous MSG treatment also induced a 56% reduction in exploratory head dips in a holeboard (P = 0.009), and a non-significant tendency for decreased burrowing behaviour (P = 0.085). These effects occurred in the absence of MSG-induced obesity or gross locomotor deficits. The findings point to subcutaneous MSG administration in early life as a cause of tau pathology and compromised species-typical behaviour in rodents. Determining whether MSG can be useful in modelling AD requires further studies of longer duration and full behavioural characterization. |
| first_indexed | 2024-12-17T21:45:02Z |
| format | Article |
| id | doaj.art-857b4664e8214120868a307669096703 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T21:45:02Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-857b4664e8214120868a3076690967032022-12-21T21:31:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01148e022072010.1371/journal.pone.0220720Cortical tau burden and behavioural dysfunctions in mice exposed to monosodium glutamate in early life.Passainte S HassaanAbeer E DiefTeshreen M ZeitounAzza M BarakaRobert M J DeaconAmany ElshorbagyAlthough monosodium glutamate (MSG)-induced neurotoxicity has been recognized for decades, the potential similarities of the MSG model to Alzheimer's disease (AD)-type neuropathology have only recently been investigated. MSG-treated mice were examined behaviourally and histologically in relation to some features of AD. Four-week old mice received 5 subcutaneous MSG (2 g/kg) injections on alternate days, or saline. At age 10-12 weeks, they were given a battery of behavioural tests for species-typical behaviours and working memory. The mice were killed at 12 weeks and the brains excised. Accumulation of hyperphosphorylated tau protein was assessed in cortical and hippocampal neurons by immunohistochemistry, and in cerebral cortical homogenates. A 78% increase in cortical concentrations of phosphorylated tau protein was observed in the MSG mice. Intracellular hyperphosphorylated tau immunostaining was observed diffusely in the cortex and hippocampus, together with cortical atrophic neurons, extensive vacuolation and dysmorphic neuropil suggestive of spongiform neurodegeneration. Nest-building was significantly impaired, and spontaneous T-maze alternation was reduced, suggesting defective short-term working memory. Subcutaneous MSG treatment also induced a 56% reduction in exploratory head dips in a holeboard (P = 0.009), and a non-significant tendency for decreased burrowing behaviour (P = 0.085). These effects occurred in the absence of MSG-induced obesity or gross locomotor deficits. The findings point to subcutaneous MSG administration in early life as a cause of tau pathology and compromised species-typical behaviour in rodents. Determining whether MSG can be useful in modelling AD requires further studies of longer duration and full behavioural characterization.https://doi.org/10.1371/journal.pone.0220720 |
| spellingShingle | Passainte S Hassaan Abeer E Dief Teshreen M Zeitoun Azza M Baraka Robert M J Deacon Amany Elshorbagy Cortical tau burden and behavioural dysfunctions in mice exposed to monosodium glutamate in early life. PLoS ONE |
| title | Cortical tau burden and behavioural dysfunctions in mice exposed to monosodium glutamate in early life. |
| title_full | Cortical tau burden and behavioural dysfunctions in mice exposed to monosodium glutamate in early life. |
| title_fullStr | Cortical tau burden and behavioural dysfunctions in mice exposed to monosodium glutamate in early life. |
| title_full_unstemmed | Cortical tau burden and behavioural dysfunctions in mice exposed to monosodium glutamate in early life. |
| title_short | Cortical tau burden and behavioural dysfunctions in mice exposed to monosodium glutamate in early life. |
| title_sort | cortical tau burden and behavioural dysfunctions in mice exposed to monosodium glutamate in early life |
| url | https://doi.org/10.1371/journal.pone.0220720 |
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