Cord serum brain-derived neurotrophic factor levels at birth associate with temperament outcomes at one year

Dingsdale, Hayley; Garay, Samantha M.; Tyson, Hannah R.; Savory, Katrina A.; Sumption, Lorna A.; Kelleher, Jemima; Langley, Kate; Goozen, Stephanie van; Roshan, John

doi:10.1016/j.jpsychires.2022.03.009

Cited by 4 publications

(1 citation statement)

References 69 publications

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“…In this regard, our results showed that BTBR animals had decreased NGF and BDNF expression levels in HIPP, a brain region in which such neurotrophins are mainly present [ 88 ]. Accordingly, hippocampal BDNF and NGF deficiency has been associated with ASD development [ 89 , 90 ], however results are contrasting, since BDNF brain levels fluctuations have been reported in response to several known, such as brain areas and age, and unknown factors [ 91 ]. In addition, NGF levels were reduced also in AMY, a brain region in which NGF signalling has been linked to stress, reward and neuroprotection [ 92 ].…”

Section: Discussionmentioning

confidence: 99%

Amygdalar neurotransmission alterations in the BTBR mice model of idiopathic autism

Bove,

Palmieri,

Santoro

et al. 2024

Transl Psychiatry

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Autism Spectrum Disorders (ASD) are principally diagnosed by three core behavioural symptoms, such as stereotyped repertoire, communication impairments and social dysfunctions. This complex pathology has been linked to abnormalities of corticostriatal and limbic circuits. Despite experimental efforts in elucidating the molecular mechanisms behind these abnormalities, a clear etiopathogenic hypothesis is still lacking. To this aim, preclinical studies can be really helpful to longitudinally study behavioural alterations resembling human symptoms and to investigate the underlying neurobiological correlates. In this regard, the BTBR T+ Itpr3tf/J (BTBR) mice are an inbred mouse strain that exhibits a pattern of behaviours well resembling human ASD-like behavioural features. In this study, the BTBR mice model was used to investigate neurochemical and biomolecular alterations, regarding Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF), together with GABAergic, glutamatergic, cholinergic, dopaminergic and noradrenergic neurotransmissions and their metabolites in four different brain areas, i.e. prefrontal cortex, hippocampus, amygdala and hypothalamus. In our results, BTBR strain reported decreased noradrenaline, acetylcholine and GABA levels in prefrontal cortex, while hippocampal measurements showed reduced NGF and BDNF expression levels, together with GABA levels. Concerning hypothalamus, no differences were retrieved. As regarding amygdala, we found reduced dopamine levels, accompanied by increased dopamine metabolites in BTBR mice, together with decreased acetylcholine, NGF and GABA levels and enhanced glutamate content. Taken together, our data showed that the BTBR ASD model, beyond its face validity, is a useful tool to untangle neurotransmission alterations that could be underpinned to the heterogeneous ASD-like behaviours, highlighting the crucial role played by amygdala.

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Section: Discussionmentioning

confidence: 99%

Amygdalar neurotransmission alterations in the BTBR mice model of idiopathic autism

Bove,

Palmieri,

Santoro

et al. 2024

Transl Psychiatry

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BDNF and KISS-1 Levels in Maternal Serum, Umbilical Cord, and Placenta: The Potential Role of Maternal Levels as Effect Biomarker

Granitzer,

Widhalm,

Atteneder

et al. 2023

Expo Health

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Brain-derived neurotrophic factor (BDNF) and kisspeptin-1 (KISS-1) regulate placental development and fetal growth. The predictive value of maternal serum BDNF and KISS-1 concentrations for placental and umbilical cord levels has not yet been explored. The influence of prenatal lead (Pb) and cadmium (Cd) exposure and maternal iron status on BDNF and KISS-1 levels is also unclarified and of concern. In a pilot cross-sectional study with 65 mother–newborn pairs, we analyzed maternal and cord serum levels of pro-BDNF, mature BDNF, and KISS-1, BDNF, and KISS-1 gene expression in placenta, Pb and Cd in maternal and umbilical cord blood (erythrocytes), and placenta. We conducted a series of in vitro experiments using human primary trophoblast cells (hTCs) and BeWo cells to verify main findings of the epidemiological analysis. Strong and consistent correlations were observed between maternal serum levels of pro-BDNF, mature BDNF, and KISS-1 and corresponding levels in umbilical serum and placental tissue. Maternal red blood cell Pb levels were inversely correlated with serum and placental KISS-1 levels. Lower expression and release of KISS-1 was also observed in Pb-exposed BeWo cells. In vitro Pb exposure also reduced cellular BDNF levels. Cd-treated BeWo cells showed increased pro-BDNF levels. Low maternal iron status was positively associated with low BDNF levels. Iron-deficient hTCs and BeWo cells showed a consistent decrease in the release of mature BDNF. The correlations between maternal BDNF and KISS-1 levels, placental gene expression, and umbilical cord serum levels, respectively, indicate the strong potential of maternal serum as predictive matrix for BDNF and KISS-1 levels in placentas and fetal sera. Pb exposure and iron status modulate BDNF and KISS-1 levels, but a clear direction of modulations was not evident. The associations need to be confirmed in a larger sample and validated in terms of placental and neurodevelopmental function.

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Prenatal Gut Microbiota Predicts Temperament in Offspring at 1–2 Years

Cao,

Zhang,

Zhang

et al. 2024

Biological Research For Nursing

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The purpose of this study was to explore whether prenatal gut microbiota (GM) and its functions predict the development of offspring temperament. A total of 53 mothers with a 1-year-old child and 41 mothers with a 2-year-old child were included in this study using a mother-infant cohort from central China. Maternal fecal samples collected during the third trimester were analyzed using 16S rRNA V3-V4 gene sequences. Temperament of the child was measured by self-reported data according to the primary caregiver. The effects of GM in mothers on offspring’s temperament were evaluated using multiple linear regression models. The results demonstrated that the alpha diversity index Simpson of prenatal GM was positively associated with the activity level of offspring at 1 year (adj. P = .036). Bifidobacterium was positively associated with high-intensity pleasure characteristics of offspring at 1 year (adj. P = .031). Comparatively, the presence of Bifidobacterium found in the prenatal microbiome was associated with low-intensity pleasure characteristics in offspring at 2 years (adj. P = .031). There were many significant associations noted among the functional pathways of prenatal GM and temperament of offspring at 2 years. Our findings support the maternal-fetal GM axis in the setting of fetal-placental development with subsequent postnatal neurocognitive developmental outcomes, and suggest that early childhood temperament is in part associated with specific GM in the prenatal setting.

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Cord serum brain-derived neurotrophic factor levels at birth associate with temperament outcomes at one year

Cited by 4 publications

References 69 publications

Amygdalar neurotransmission alterations in the BTBR mice model of idiopathic autism

Amygdalar neurotransmission alterations in the BTBR mice model of idiopathic autism

BDNF and KISS-1 Levels in Maternal Serum, Umbilical Cord, and Placenta: The Potential Role of Maternal Levels as Effect Biomarker

Prenatal Gut Microbiota Predicts Temperament in Offspring at 1–2 Years

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