Brain serotonin and serotonin transporter expression in male and female postnatal rat offspring in response to perturbed early life dietary exposures
IntroductionSerotonin (5-HT) is critical for neurodevelopment and the serotonin transporter (SERT) modulates serotonin levels. Perturbed prenatal and postnatal dietary exposures affect the developing offspring predisposing to neurobehavioral disorders in the adult. We hypothesized that the postnatal...
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2024.1363094/full |
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| author | Xin Ye Shubhamoy Ghosh Bo-Chul Shin Amit Ganguly Liesbeth Maggiotto Jonathan P. Jacobs Jonathan P. Jacobs Sherin U. Devaskar |
| author_facet | Xin Ye Shubhamoy Ghosh Bo-Chul Shin Amit Ganguly Liesbeth Maggiotto Jonathan P. Jacobs Jonathan P. Jacobs Sherin U. Devaskar |
| author_sort | Xin Ye |
| collection | DOAJ |
| description | IntroductionSerotonin (5-HT) is critical for neurodevelopment and the serotonin transporter (SERT) modulates serotonin levels. Perturbed prenatal and postnatal dietary exposures affect the developing offspring predisposing to neurobehavioral disorders in the adult. We hypothesized that the postnatal brain 5-HT-SERT imbalance associated with gut dysbiosis forms the contributing gut-brain axis dependent mechanism responsible for such ultimate phenotypes.MethodsEmploying maternal diet restricted (IUGR, n=8) and high fat+high fructose (HFhf, n=6) dietary modifications, rodent brain serotonin was assessed temporally by ELISA and SERT by quantitative Western blot analysis. Simultaneously, colonic microbiome studies were performed.ResultsAt early postnatal (P) day 2 no changes in the IUGR, but a ~24% reduction in serotonin (p = 0.00005) in the HFhf group occurred, particularly in the males (p = 0.000007) revealing a male versus female difference (p = 0.006). No such changes in SERT concentrations emerged. At late P21 the IUGR group reared on HFhf (IUGR/HFhf, (n = 4) diet revealed increased serotonin by ~53% in males (p = 0.0001) and 36% in females (p = 0.023). While only females demonstrated a ~40% decrease in serotonin (p = 0.010), the males only trended lower without a significant change within the HFhf group (p = 0.146). SERT on the other hand was no different in HFhf or IUGR/RC, with only the female IUGR/HFhf revealing a 28% decrease (p = 0.036). In colonic microbiome studies, serotonin-producing Bacteriodes increased with decreased Lactobacillus at P2, while the serotonin-producing Streptococcus species increased in IUGR/HFhf at P21. Sex-specific changes emerged in association with brain serotonin or SERT in the case of Alistipase, Anaeroplasma, Blautia, Doria, Lactococcus, Proteus, and Roseburia genera.Discussion We conclude that an imbalanced 5-HT-SERT axis during postnatal brain development is sex-specific and induced by maternal dietary modifications related to postnatal gut dysbiosis. We speculate that these early changes albeit transient may permanently alter critical neural maturational processes affecting circuitry formation, thereby perturbing the neuropsychiatric equipoise. |
| first_indexed | 2024-04-24T21:43:40Z |
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| institution | Directory Open Access Journal |
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| last_indexed | 2024-04-24T21:43:40Z |
| publishDate | 2024-03-01 |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-719f5033147341eca5139c60f310502c2024-03-21T04:32:08ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2024-03-011810.3389/fnins.2024.13630941363094Brain serotonin and serotonin transporter expression in male and female postnatal rat offspring in response to perturbed early life dietary exposuresXin Ye0Shubhamoy Ghosh1Bo-Chul Shin2Amit Ganguly3Liesbeth Maggiotto4Jonathan P. Jacobs5Jonathan P. Jacobs6Sherin U. Devaskar7Department of Pediatrics, Division of Neonatology & Developmental Biology and The Neonatal Research Center of the Children's Discovery & Innovation Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesDepartment of Pediatrics, Division of Neonatology & Developmental Biology and The Neonatal Research Center of the Children's Discovery & Innovation Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesDepartment of Pediatrics, Division of Neonatology & Developmental Biology and The Neonatal Research Center of the Children's Discovery & Innovation Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesDepartment of Pediatrics, Division of Neonatology & Developmental Biology and The Neonatal Research Center of the Children's Discovery & Innovation Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesDepartment of Pediatrics, Division of Neonatology & Developmental Biology and The Neonatal Research Center of the Children's Discovery & Innovation Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesThe Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesDivision of Gastroenterology, Hepatology and Parenteral Nutrition, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, United StatesDepartment of Pediatrics, Division of Neonatology & Developmental Biology and The Neonatal Research Center of the Children's Discovery & Innovation Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesIntroductionSerotonin (5-HT) is critical for neurodevelopment and the serotonin transporter (SERT) modulates serotonin levels. Perturbed prenatal and postnatal dietary exposures affect the developing offspring predisposing to neurobehavioral disorders in the adult. We hypothesized that the postnatal brain 5-HT-SERT imbalance associated with gut dysbiosis forms the contributing gut-brain axis dependent mechanism responsible for such ultimate phenotypes.MethodsEmploying maternal diet restricted (IUGR, n=8) and high fat+high fructose (HFhf, n=6) dietary modifications, rodent brain serotonin was assessed temporally by ELISA and SERT by quantitative Western blot analysis. Simultaneously, colonic microbiome studies were performed.ResultsAt early postnatal (P) day 2 no changes in the IUGR, but a ~24% reduction in serotonin (p = 0.00005) in the HFhf group occurred, particularly in the males (p = 0.000007) revealing a male versus female difference (p = 0.006). No such changes in SERT concentrations emerged. At late P21 the IUGR group reared on HFhf (IUGR/HFhf, (n = 4) diet revealed increased serotonin by ~53% in males (p = 0.0001) and 36% in females (p = 0.023). While only females demonstrated a ~40% decrease in serotonin (p = 0.010), the males only trended lower without a significant change within the HFhf group (p = 0.146). SERT on the other hand was no different in HFhf or IUGR/RC, with only the female IUGR/HFhf revealing a 28% decrease (p = 0.036). In colonic microbiome studies, serotonin-producing Bacteriodes increased with decreased Lactobacillus at P2, while the serotonin-producing Streptococcus species increased in IUGR/HFhf at P21. Sex-specific changes emerged in association with brain serotonin or SERT in the case of Alistipase, Anaeroplasma, Blautia, Doria, Lactococcus, Proteus, and Roseburia genera.Discussion We conclude that an imbalanced 5-HT-SERT axis during postnatal brain development is sex-specific and induced by maternal dietary modifications related to postnatal gut dysbiosis. We speculate that these early changes albeit transient may permanently alter critical neural maturational processes affecting circuitry formation, thereby perturbing the neuropsychiatric equipoise.https://www.frontiersin.org/articles/10.3389/fnins.2024.1363094/fullserotoninserotonin transportercaloric restrictionintrauterine growth restrictionhigh fat dietmicrobiome |
| spellingShingle | Xin Ye Shubhamoy Ghosh Bo-Chul Shin Amit Ganguly Liesbeth Maggiotto Jonathan P. Jacobs Jonathan P. Jacobs Sherin U. Devaskar Brain serotonin and serotonin transporter expression in male and female postnatal rat offspring in response to perturbed early life dietary exposures Frontiers in Neuroscience serotonin serotonin transporter caloric restriction intrauterine growth restriction high fat diet microbiome |
| title | Brain serotonin and serotonin transporter expression in male and female postnatal rat offspring in response to perturbed early life dietary exposures |
| title_full | Brain serotonin and serotonin transporter expression in male and female postnatal rat offspring in response to perturbed early life dietary exposures |
| title_fullStr | Brain serotonin and serotonin transporter expression in male and female postnatal rat offspring in response to perturbed early life dietary exposures |
| title_full_unstemmed | Brain serotonin and serotonin transporter expression in male and female postnatal rat offspring in response to perturbed early life dietary exposures |
| title_short | Brain serotonin and serotonin transporter expression in male and female postnatal rat offspring in response to perturbed early life dietary exposures |
| title_sort | brain serotonin and serotonin transporter expression in male and female postnatal rat offspring in response to perturbed early life dietary exposures |
| topic | serotonin serotonin transporter caloric restriction intrauterine growth restriction high fat diet microbiome |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2024.1363094/full |
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