DIETARY RESCUE OF ADULT BEHAVIORAL DEFICITS IN THE<i>FMR1</i>KNOCKOUT MOUSE
ABSTRACT The current study aimed to further address important questions regarding the therapeutic efficacy of omega-3 fatty acids for various behavioral and neuroimmune aspects of theFmr1phenotype. To address these questions, our experimental design utilized two different omega-3 fatty acid administration timepoints, compared to both standard laboratory chow controls (“Standard”) and a diet controlling for the increase in fat content (“Control Fat”). In the first paradigm, post-weaning supplementation (after postnatal day 21) with the omega-3 fatty acid diet (“Omega-3”) reversed deficits in startle threshold, but not deficits in prepulse inhibition, and the effect on startle threshold was not specific to the Omega-3 diet. However, post-weaning supplementation with both experimental diets also impaired acquisition of a fear response, recall of the fear memory and contextual fear conditioning compared to the Standard diet. The post-weaning Omega-3 diet reduced hippocampal expression of IL-6 and this reduction of IL-6 was significantly associated with diminished performance in the fear conditioning task. In the prenatal experimental paradigm, the Omega-3 diet attenuated hyperactivity and acquisition of a fear response. Additionally, prenatal exposure to the Control Fat diet (similar to a “Western” diet) further diminished nonsocial anxiety in theFmr1knockout. This study provides significant evidence that dietary fatty acids throughout the lifespan can significantly impact the behavioral and neuroimmune phenotype of theFmr1knockout model..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 02. Nov. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nolan, Suzanne O. [VerfasserIn] |
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| doi: |
10.1101/2021.04.16.440191 |
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| PPN (Katalog-ID): |
XBI020376324 |
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| 520 | |a ABSTRACT The current study aimed to further address important questions regarding the therapeutic efficacy of omega-3 fatty acids for various behavioral and neuroimmune aspects of theFmr1phenotype. To address these questions, our experimental design utilized two different omega-3 fatty acid administration timepoints, compared to both standard laboratory chow controls (“Standard”) and a diet controlling for the increase in fat content (“Control Fat”). In the first paradigm, post-weaning supplementation (after postnatal day 21) with the omega-3 fatty acid diet (“Omega-3”) reversed deficits in startle threshold, but not deficits in prepulse inhibition, and the effect on startle threshold was not specific to the Omega-3 diet. However, post-weaning supplementation with both experimental diets also impaired acquisition of a fear response, recall of the fear memory and contextual fear conditioning compared to the Standard diet. The post-weaning Omega-3 diet reduced hippocampal expression of IL-6 and this reduction of IL-6 was significantly associated with diminished performance in the fear conditioning task. In the prenatal experimental paradigm, the Omega-3 diet attenuated hyperactivity and acquisition of a fear response. Additionally, prenatal exposure to the Control Fat diet (similar to a “Western” diet) further diminished nonsocial anxiety in theFmr1knockout. This study provides significant evidence that dietary fatty acids throughout the lifespan can significantly impact the behavioral and neuroimmune phenotype of theFmr1knockout model. | ||
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