Large neutral amino acid levels tune perinatal neuronal excitability and survival

Knaus, Lisa S.; Basilico, Bernadette; Malzl, Daniel; Bujalkova, Maria Gerykova; Smogavec, Mateja; Schwarz, Lena A.; Gorkiewicz, Sarah; Amberg, Nicole; Pauler, Florian M.; Knittl-Frank, Christian; Tassinari, Marianna; Maulide, Nuno; Rülicke, Thomas; Menche, Jörg; Hippenmeyer, Simon; Novarino, Gaia

doi:10.1016/j.cell.2023.02.037

Cited by 26 publications

(9 citation statements)

References 94 publications

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“…Many studies show that exposure to PM 2.5 is associated with reduced glutathione (GSH) levels, suggesting that PM 2.5 exposure may induce oxidative stress. , Oxidative stress can activate mTORC1 signaling through several mechanisms, such as promoting GSH synthesis and protein translation, eventually leading to the elevated expression of amino acids. − Our present study shows that threonine mediates a considerable proportion of the inverse association between specific PM 2.5 constituents and NBNA scores. In support of our findings, previous epidemiological studies demonstrated that PM 2.5 may disrupt plasma threonine and threonine metabolism pathways, which play a critical role in mTOR activity and certain stages of brain development. ,,, …”

Section: Discussionsupporting

confidence: 91%

“…For instance, glutamate, aspartate, and histamine are the major neurotransmitters to modulate synaptic plasticity, neuronal activity, learning, motor control, motivational behavior, emotion, and executive function . Some amino acids such as leucine and threonine play key roles in certain stages of brain development effect . Disorders in these amino acid productions may affect the development of the nervous system by inhibiting mTOR activity, reducing organoid size, and altering gene expression .…”

Section: Discussionmentioning

confidence: 99%

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Gestational Exposure to PM_2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study

Lu,

Liu,

Chen

et al. 2024

Environ. Sci. Technol.

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Exposure to fine particulate matter (PM2.5) during pregnancy has been inversely associated with neonatal neurological development. However, the associations of exposure to specific PM2.5 constituents with neonatal neurological development remain unclear. We investigated these associations and examined the mediating role of meconium metabolites in a Chinese birth cohort consisting of 294 mother–infant pairs. Our results revealed that exposure to PM2.5 and its specific constituents (i.e., organic matter, black carbon, sulfate, nitrate, and ammonium) in the second trimester, but not in the first or third trimester, was inversely associated with the total neonatal behavioral neurological assessment (NBNA) scores. The PM2.5 constituent mixture in the second trimester was also inversely associated with NBNA scores, and sulfate was identified as the largest contributor. Furthermore, meconium metabolome analysis identified four metabolites, namely, threonine, lysine, leucine, and saccharopine, that were associated with both PM2.5 constituents and NBNA scores. Threonine was identified as an important mediator, accounting for a considerable proportion (14.53–15.33%) of the observed inverse associations. Our findings suggest that maternal exposure to PM2.5 and specific constituents may adversely affect neonatal behavioral development, in which meconium metabolites may play a mediating role.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Gestational Exposure to PM_2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study

Lu,

Liu,

Chen

et al. 2024

Environ. Sci. Technol.

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“…[113] Similar to these diseases that are mostly diagnosed in adulthood, neurodevelopmental disorders, such as autism spectrum disorder and schizophrenia, are also reported to have vascular disfunction. [113] Since perinatal metabolic changes significantly affect the survival and wiring of cortical neurons, [114] the correct development of blood vessels in the brain is critical for proper CNS development. In addition, dysfunctions of glial cells in neurodevelopmental and degenerative disorders have also been reported.…”

Section: Discussionmentioning

confidence: 99%

Interactions between neural cells and blood vessels in central nervous system development

Morimoto,

Tabata,

Takahashi

et al. 2023

BioEssays

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The sophisticated function of the central nervous system (CNS) is largely supported by proper interactions between neural cells and blood vessels. Accumulating evidence has demonstrated that neurons and glial cells support the formation of blood vessels, which in turn, act as migratory scaffolds for these cell types. Neural progenitors are also involved in the regulation of blood vessel formation. This mutual interaction between neural cells and blood vessels is elegantly controlled by several chemokines, growth factors, extracellular matrix, and adhesion molecules such as integrins. Recent research has revealed that newly migrating cell types along blood vessels repel other preexisting migrating cell types, causing them to detach from the blood vessels. In this review, we discuss vascular formation and cell migration, particularly during development. Moreover, we discuss how the crosstalk between blood vessels and neurons and glial cells could be related to neurodevelopmental disorders.

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“…17,18 Lower levels of leucine can cause dysplasia in the brain. 19 Then, we undertook exogenous leucine supplementation experiments to corroborate these findings.…”

Section: Introductionmentioning

confidence: 89%

Revealing the role of leucine in improving the social avoidance behavior of depression through a combination of untargeted and targeted metabolomics

Wang¹,

Wu²,

Xiang³

et al. 2023

Food Funct.

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Large neutral amino acid levels tune perinatal neuronal excitability and survival

Cited by 26 publications

References 94 publications

Gestational Exposure to PM_2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study

Gestational Exposure to PM_2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study

Interactions between neural cells and blood vessels in central nervous system development

Revealing the role of leucine in improving the social avoidance behavior of depression through a combination of untargeted and targeted metabolomics

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Large neutral amino acid levels tune perinatal neuronal excitability and survival

Cited by 26 publications

References 94 publications

Gestational Exposure to PM2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study

Gestational Exposure to PM2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study

Interactions between neural cells and blood vessels in central nervous system development

Revealing the role of leucine in improving the social avoidance behavior of depression through a combination of untargeted and targeted metabolomics

Contact Info

Product

Resources

About

Gestational Exposure to PM_2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study

Gestational Exposure to PM_2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study