Prenatal High-Fat Diet Rescues Communication Deficits in Fmr1 Mutant Mice in a Sex-Specific Manner
Open accessAbstract
Using high-throughput analysis methods, the present study sought to determine the impact of prenatal high-fat dietary manipulations on isolation-induced ultrasonic vocalization production in both male and female Fmr1mutants on postnatal day 9. Prior to breeding, male FVB/129 Fmr1 wildtype and female Fmr1 heterozygous breeding pairs were assigned to 1 of 3 diet conditions: standard lab chow, omega-3 fatty acid-enriched chow, and a diet controlling for the fat increase. Prenatal exposure to omega-3 fatty acids improved reductions in the number of calls produced by Fmr1heterozygotes females. Moreover, diminished spectral purity in the female Fmr1homozygous mouse was rescued by exposure to both high-fat diets, although these effects were not seen in the male Fmr1knockout. Prenatal dietary fat manipulation also influenced several other aspects of vocalization production, such as the number of calls produced and their fundamental frequency, aside from effects due to loss of Fmr1.Specifically, in males, regardless of genotype, prenatal exposure to high omega-3s increased the average fundamental frequency of calls. These data support the need for future preclinical and clinical work elucidating the full potential of prenatal high-fat diets as a novel therapeutic alternative forFragile X syndrome.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
n-3 polyunsaturated fatty acid supplementation has beneficial effects on the behavioral phenotype of Fmr1 KO mice.
“n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has beneficial effects on the behavioral phenotype of the Fmr1 KO mice24,25.”
From An iPSC-derived astrocyte model of fragile X syndrome exhibits dysregulated cholesterol homeostasis (2023) · cites this paper as [25]
The Results (page unavailable) report that prenatal omega-3-enriched diet ameliorated reduced vocalization spectral purity in female Fmr1 knockout pups. The claim is broader than this finding: the same section says a control high-fat diet also ameliorated spectral purity, while omega-3 exposure decreased the number of calls in female knockouts. The male Results section reports no genotype-by-diet interaction for the vocalization measures tested. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Bilousova, T. V., Dansie, L., Ngo, M., Aye, J., Charles, J. R., Ethell, D. W., & Ethell, I. M. (2009) · Journal of Medical Genetics · doi:10.1136/jmg.2008.061796 · Cited by 465 · see citing works
Maternal dietary docosahexanoic acid content affects the rat pup auditory system
Haubner, L. Y., Stockard, J. E., Saste, M. D., Benford, V. J., Phelps, C. P., Chen, L. T., Barness, L., Wiener, D., & Carver, J. D. (2002) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00764-x · Cited by 62 · see citing works
Flagged first, then by citations
Research works printed but not linked: 51
- [2]Venuti P, Caria A, Esposito G, De Pisapia N, Bornstein MH, de Falco S. Differential brain responses to cries of infants with autistic disorder and typical development: an fMRI study. Res Dev Disabil. 2012 2012; 33(6): 2255– 64. 22835685 PMC3496246
- [3]Esposito G, Hiroi N, Scattoni ML. Cry, Baby, Cry: Expression of Distress As a Biomarker and Modulator in Autism Spectrum Disorder. Int J Neuropsychopharmacol. 2017 2017; 20(6): 498– 503. PMC5458334 28204487
- [4]Branchi I, Santucci D, Alleva E. Ultrasonic vocalisation emitted by infant rodents: a tool for assessment of neurobehavioural development. Behavioural brain research. 2001 11 1; 125(1–2): 49– 56. 11682093
- [5]Smith JC. Responses of adult mice to models of infant calls. J Comp Physiol Psych. 1976; 90(12): 1105.
- [6]Branchi I, Santucci D, Alleva E. Analysis of ultrasonic vocalizations emitted by infant rodents. Current Protocols in Toxicology. 2006; 30(1): 13.12.1– 13.12.14. 23045127
- [7]Keller A, Saucier D, Sheerin A, Yager J. Febrile convulsions affect ultrasonic vocalizations in the rat pup. Epilepsy Behav. 2004 2004/10; 5(5): 649– 54. 15380115
- [8]Cox ET, Hodge CW, Sheikh MJ, Abramowitz AC, Jones GF, Jamieson-Drake AW, Delayed developmental changes in neonatal vocalizations correlates with variations in ventral medial hypothalamus and central amygdala development in the rodent infant: Effects of prenatal cocaine. Behav Brain Res. 2012 2012; 235(2): 166– 75. 22867871 PMC3461834
- [9]Malkova NV, Yu CZ, Hsiao EY, Moore MJ, Patterson PH. Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism. Brain Behav Immun. 2012 2012/5; 26(4): 607– 16. 22310922 PMC3322300
- [10]Rotschafer SE, Trujillo MS, Dansie LE, Ethell IM, Razak KA. Minocycline treatment reverses ultrasonic vocalization production deficit in a mouse model of Fragile X Syndrome. Brain Res. 2012 2012; 1439: 7– 14. 22265702
- [11]Reynolds CD, Nolan SO, Jefferson T, Lugo JN. Sex-specific and genotype-specific differences in vocalization development in FMR1 knockout mice. Neuroreport. 2016 12 14; 27(18): 1331– 35. 27824730 PMC5290539
- [12]Binder MS, Lugo JN. NS-Pten knockout mice show sex- and age-specific differences in ultrasonic vocalizations. Brain Behav. 2017 2017; 7(11): e00857– e57. 29201556 PMC5698873
- [13]Nolan SO, Hodges SL, Condon SM, Muhammed IDA, Tomac LA, Binder MS, High seizure load during sensitive periods of development leads to broad shifts in ultrasonic vocalization behavior in neonatal male and female C57BL/6J mice. Epilepsy Behav. 2019 2019/6/1; 95: 26– 33. 31022661 PMC6546518
- [14]Turner G, Webb T, Wake S, Robinson H. Prevalence of fragile X syndrome. Am J Med Genet. 1996 1996; 64(1): 196– 97. 8826475
- [15]Kaufmann WE, Cortell R, Kau ASM, Bukelis I, Tierney E, Gray RM, Autism spectrum disorder in fragile X syndrome: communication, social interaction, and specific behaviors. Am J Med Genet A. 2004 2004; 129A(3): 225– 34. 15326621
- [16]Bakker. Fmr1 knockout mice: a model to study fragile X mental retardation. The Dutch-Belgian Fragile X Consortium. Cell. 1994 1994; 78(1): 23– 33. 8033209
- [17]D’Hooge R, Nagels G, Franck F, Bakker CE, Reyniers E, Storm K, Mildly impaired water maze performance in male Fmr1 knockout mice. Neuroscience. 1997 1997; 76(2): 367– 76. 9015322
- [18]de Vrij FMS, Levenga J, van der Linde HC, Koekkoek SK, De Zeeuw CI, Nelson DL, Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice. Neurobiol Dis. 2008 2008; 31(1): 127– 32. 18571098 PMC2481236
- [20]Baker KB, Wray SP, Ritter R, Mason S, Lanthorn TH, Savelieva KV. Male and female Fmr1 knockout mice on C57 albino background exhibit spatial learning and memory impairments. Genes Brain Behav. 2010 2010/8; 9(6): 562– 74. 20398059
- [21]Ding Q, Sethna F, Wang H. Behavioral analysis of male and female Fmr1 knockout mice on C57BL/6 background. Behavioural brain research. 2014 9 1; 271: 72– 8. 24886775 PMC4104211
- [22]Nolan SO, Reynolds CD, Smith GD, Holley AJ, Escobar B, Chandler MA, Deletion of Fmr1 results in sex-specific changes in behavior. Brain Behav. 2017 2017/10; 7(10): e00800. 29075560 PMC5651384
- [24]Abbeduto L, Hagerman RJ. Language and communication in fragile X syndrome. Mental Retardation and Developmental Disabilities Research Reviews. 1997; 3(4): 313– 22.
- [25]Belagodu AP, Johnson AM, Galvez R. Characterization of ultrasonic vocalizations of fragile X mice. Behav Brain Res. 2016 2016. 27142239
- [26]Hodges SL, Nolan SO, Reynolds CD, Lugo JN. Spectral and temporal properties of calls reveal deficits in ultrasonic vocalizations of adult Fmr1 knockout mice. Behav Brain Res. 2017 2017; 332: 50– 58. 28552599 PMC6503674
- [27]Roy S, Watkins N, Heck D. Comprehensive analysis of ultrasonic vocalizations in a mouse model of fragile X syndrome reveals limited, call type specific deficits. PLoS One. 2012 2012; 7(9): e44816. 22984567 PMC3439444
- [28]Lai JK, Sobala-Drozdowski M, Zhou L, Doering LC, Faure PA, Foster JA. Temporal and spectral differences in the ultrasonic vocalizations of fragile X knock out mice during postnatal development. Behav Brain Res. 2014 2014; 259: 119– 30. 24211451
- [29]Nolan SO, Hodges SL, Lugo JN. High-throughput analysis of vocalizations reveals sex-specific changes in Fmr1 mutant pups. Genes, Brain and Behavior. 2019. PMC12939262 31587487
- [30]Pietropaolo S, Goubran MG, Joffre C, Aubert A, Lemaire-Mayo V, Crusio WE, Dietary supplementation of omega-3 fatty acids rescues fragile X phenotypes in Fmr1-Ko mice. Psychoneuroendocrinology. 2014 11; 49: 119– 29. 25080404
- [31]Chabout J, Jones-Macopson J, Jarvis ED. Eliciting and analyzing male mouse ultrasonic vocalization (USV) songs. Journal of visualized experiments: JoVE. 2017 5 09(123). PMC5607930 28518074
- [32]Nolan SO, Hodges SL, Condon SM, Muhammed IDA, Tomac LA, Binder MS, High seizure load during sensitive periods of development leads to broad shifts in ultrasonic vocalization behavior in neonatal male and female C57BL/6J mice. Epilepsy & Behavior. 2019 2019/06/01/; 95: 26– 33. 31022661 PMC6546518
- [33]Chabout J, Sarkar A, Dunson DB, Jarvis ED. Male mice song syntax depends on social contexts and influences female preferences. Frontiers in behavioral neuroscience. 2015; 9: 76– 76. 25883559 PMC4383150
- [34]Arriaga G, Zhou EP, Jarvis ED. Of mice, birds, and men: The mouse ultrasonic song system has some features similar to humans and song-learning birds. PLoS One. 2012; 7(10): e46610. 23071596 PMC3468587
- [35]Arriaga G, Jarvis ED. Mouse vocal communication system: Are ultrasounds learned or innate? Brain and Language. 2013 2013/01/01/; 124(1): 96– 116. 23295209 PMC3886250
- [36]Janik VM, Slater PJ. The different roles of social learning in vocal communication. Animal behaviour. 2000 7; 60(1): 1– 11. 10924198
- [37]Jarvis ED. Learned birdsong and the neurobiology of human language. Ann N Y Acad Sci. 2004 2004/6; 1016: 749– 77. 15313804 PMC2485240
- [38]Hammerschmidt K, Whelan G, Eichele G, Fischer J. Mice lacking the cerebral cortex develop normal song: insights into the foundations of vocal learning. Scientific reports. 2015 3 06; 5: 8808. 25744204 PMC4351519
- [39]Hammerschmidt K, Whelan G, Eichele G, Fischer J. Mice lacking the cerebral cortex develop normal song: insights into the foundations of vocal learning. Scientific Reports. 2015 3 06; 5: 8808. 25744204 PMC4351519
- [40]Ruby K, Falvey K, Kulesza RJ. Abnormal neuronal morphology and neurochemistry in the auditory brainstem of Fmr1 knockout rats. Neuroscience. 2015; 303: 285– 98. 26166728
- [41]Stockard JE, Saste MD, Benford VJ, Barness L, Auestad N, Carver JD. Effect of docosahexaenoic acid content of maternal diet on auditory brainstem conduction times in rat pups. Developmental Neuroscience. 2000; 22(5–6): 494– 99. 11111168
- [43]Decsi T, Kennedy K. Sex-specific differences in essential fatty acid metabolism. The American Journal Of Clinical Nutrition. 2011 12; 94(6 Suppl): 1914s– 19s. 22089435
- [44]Colquhoun I, Bunday S. A lack of essential fatty acids as a possible cause of hyperactivity in children. Medical Hypotheses. 1981 1981/05/01/; 7(5): 673– 79. 7196985
- [45]Qin M, Kang J, Smith CB. A null mutation for Fmr1 in female mice: effects on regional cerebral metabolic rate for glucose and relationship to behavior. Neuroscience. 2005; 135(3): 999– 1009. 16154294
- [46]Baker KB, Wray SP, Ritter R, Mason S, Lanthorn TH, Savelieva KV. Male and female Fmr1 knockout mice on C57 albino background exhibit spatial learning and memory impairments. Genes, Brain and Behavior. 2010; 9(6): 562– 74. 20398059
- [47]Nolan SO, Reynolds CD, Smith GD, Holley AJ, Escobar B, Chandler MA, Deletion of Fmr1 results in sex-specific changes in behavior. Brain and behavior. 2017 10; 7(10): e00800. 29075560 PMC5651384
- [48]Abuaish S, Tse EK, McGowan PO. Perinatal high-fat diet impairs pup retrieval and induces sex-specific changes in ultrasonic vocalization characteristics of rat pups. Developmental psychobiology. 2020; 62(4): 436– 45. 31564067
- [49]Grimsley JM, Monaghan JJ, Wenstrup JJ. Development of social vocalizations in mice. PloS one. 2011; 6(3). PMC3052362 21408007
- [50]Van Meer P, Raber J. Mouse behavioural analysis in systems biology. The Biochemical Journal. 2005; 389(Pt 3): 593– 610. 16035954 PMC1180709
- [51]Crabbe JC, Wahlsten D, Dudek BC. Genetics of mouse behavior: interactions with laboratory environment. Science. 1999 6 4; 284(5420): 1670– 2. 10356397
- [52]Wise A, Gilburt DJ. The variability of dietary fibre in laboratory animal diets and its relevance to the control of experimental conditions. Food and Cosmetics Toxicology. 1980 1980/01/01/; 18(6): 643– 48. 6259033
- [53]Warden CH, Fisler JS. Comparisons of diets used in animal models of high-fat feeding. Cell Metab. 2008; 7(4): 277– 77. 18396128 PMC2394560
- [54]Giles K, Guan C, Jagoe TR, Mazurak V. Diet composition as a source of variation in experimental animal models of cancer cachexia. J Cachexia Sarcopenia Muscle. 2016; 7(2): 110– 25. 27493865 PMC4863732
- [55]Abuaish S, Spinieli RL, McGowan PO. Perinatal high fat diet induces early activation of endocrine stress responsivity and anxiety-like behavior in neonates. Psychoneuroendocrinology. 2018; 98: 11– 21. 30086533
Cited by
Sorted by citations
An iPSC-derived astrocyte model of fragile X syndrome exhibits dysregulated cholesterol homeostasis
Talvio, K., Wagner, V. A., Minkeviciene, R., Kirkwood, J. S., Kulinich, A. O., Umemori, J., Bhatia, A., Hur, M., Käkelä, R., Ethell, I. M., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-05147-9 · Cited by 8 · see citing works
- Authors
- Nolan, S. O., Hodges, S. L., Okoh, J. T., Binder, M. S., & Lugo, J. N.
- Affiliations
- Baylor University (US)
- Venue
- Developmental Neuroscience
- Publisher
- S. Karger AG
- Published
- 2020
- Volume
- 42
- Issue
- 2-4
- Pages
- 94-104
- ISSN
- 0378-5866 (ISSN-L)
- 1421-9859
- PMC
- PMC7864857
- OpenAlex
- W3120373616
- Cited by
- 10
- References
- 2
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 1
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Developmental Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R15NS088776)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
- Keywords
- omega-3 fatty acids, Fmr1 knockout mice, fragile X syndrome, ultrasonic vocalizations, social communication deficits, sex differences, fundamental frequency, spectral purity, autism spectrum disorder
- MeSH terms
- Autism Spectrum Disorder, Animals, Disease Models, Animal, Female, Male, Mutation, Pregnancy, Sex Characteristics, Vocalization, Animal, Fatty Acids, Omega-3, Mice, Knockout, Prenatal Nutritional Physiological Phenomena, Mice, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1, Diet, High-Fat
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review