Perturbing maternal gut microbiota during pregnancy leads to changes in the behavior of offspring

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Enriched Expression of Serotonin 1B and 2A Receptor Genes in Macaque Visual Cortex and their Bidirectional Modulatory Effects on Neuronal Responses

To study the molecular mechanism how cortical areas are specialized in adult primates, we searched for area-specific genes in macaque monkeys and found striking enrichment of serotonin (5-hydroxytryptamine, 5-HT) 1B receptor mRNA, and to a lesser extent, of 5-HT2A receptor mRNA, in the primary visual area (V1). In situ hybridization analyses revealed that both mRNA species were highly concentrated in the geniculorecipient layers IVA and IVC, where they were coexpressed in the same neurons. Monocular inactivation by tetrodotoxin injection resulted in a strong and rapid (<3 h) downregulation of these mRNAs, suggesting the retinal activity dependency of their expression. Consistent with the high expression level in V1, clear modulatory effects of 5-HT1B and 5-HT2A receptor agonists on the responses of V1 neurons were observed in in vivo electrophysiological experiments. The modulatory effect of the 5-HT1B agonist was dependent on the firing rate of the recorded neurons: The effect tended to be facilitative for neurons with a high firing rate, and suppressive for those with a low firing rate. The 5-HT2A agonist showed opposite effects. These results suggest that this serotonergic system controls the visual response in V1 for optimization of information processing toward the incoming visual inputs

Taurine: A Maternally Derived Nutrient Linking Mother and Offspring

Mammals can obtain taurine from food and synthesize it from sulfur-containing amino acids. Mammalian fetuses and infants have little ability to synthesize taurine. Therefore, they are dependent on taurine given from mothers either via the placenta or via breast milk. Many lines of evidence demonstrate that maternally derived taurine is essential for offspring development, shaping various traits in adults. Various environmental factors, including maternal obesity, preeclampsia, and undernutrition, can affect the efficacy of taurine transfer via either the placenta or breast milk. Thus, maternally derived taurine during the perinatal period can influence the offspring&rsquo;s development and even determine health and disease later in life. In this review, I will discuss the biological function of taurine during development and the regulatory mechanisms of taurine transport from mother to offspring. I also refer to the possible environmental factors affecting taurine functions in mother-offspring bonding during perinatal periods. The possible functions of taurine as a determinant of gut microbiota and in the context of the Developmental Origins of Health and Disease (DOHaD) hypothesis will also be discussed

Perturbed maternal microbiota shapes offspring microbiota during early colonization period in mice

Recent studies have highlighted the impact of disrupted maternal gut microbiota on the colonization of offspring gut microbiota, with implications for offspring developmental trajectories. The extent to which offspring inherit the characteristics of altered maternal gut microbiota remains elusive. In this study, we employed a mouse model where maternal gut microbiota disruption was induced using non-absorbable antibiotics. Systematic chronological analyses of dam fecal samples, offspring luminal content, and offspring gut tissue samples revealed a notable congruence between offspring gut microbiota profiles and those of the perturbed maternal gut microbiota, highlighting the profound influence of maternal microbiota on early-life colonization of offspring gut microbiota. Nonetheless, certain dominant bacterial genera in maternal microbiota did not transfer to the offspring, indicating a bacterial taxonomy-dependent mechanism in the inheritance of maternal gut microbiota. Our results embody the vertical transmission dynamics of disrupted maternal gut microbiota in an animal model, where the gut microbiota of an offspring closely mirrors the gut microbiota of its mother

GAD65/67-positive cells in the meninges cover the entire developing neocortex by E14.5.

<p>(Upper panels) E12.5 developing neocortex was stained for GAD65/67 and developed with DAB. By E12.5, in the rostral region of the developing neocortex, GAD65/67-positive cells were present in the dorsal meninges, although the GAD65/67-positive cells did not cover the entire neocortex. In the middle region of the E12.5 neocortex, GAD65/67-expressing cells were present in the lateral region but not the dorsal region of the neocortex. In the mid-caudal region, the GAD65/67-expressing cells did not reach even the lateral end of the neocortex. Arrows in the upper panels indicate the dorsal ends of the distribution of GAD65/67-expressing cells in the meninges at each rostro-caudal position. (lower panels) In E14.5 sections stained for GAD65/67, the GAD65/67-expressing cells cover the entire neocortex at any position along rostro-caudal axis. Because boiling the sections in sodium citrate buffer is needed before staining with anti-GAD65/67 antibody, the sections were injured during the staining process. Bar, 5 mm.</p

GAD 65 expression is apparent from the start of the development of the choroid plexus.

<p>(A–C) The distribution of GAD65 and GAD67 in the choroid plexus on E12.5 (A), E13.5 (B) and E14.5 (C). The signals for GAD65 were observed in the epithelial cells of the choroid plexus throughout the stages examined, whilst few signals for GAD67 were detected in the developing choroid plexus. The signals for GAD65 were stable on E12.5, and the level of expression of GAD65 appeared to become higher as the development proceeds. (D) GABA distribution in the E14.5 choroid plexus. The numbers and the intensity of signals for GABA vary among the epithelial cells of choroid plexus. Some cells in the choroid plexus showed bright signals in its cytoplasm (arrows), while many cells in the epithelium of choroid plexus exhibited faint signals for GABA. CPe, choroid plexus epithelium: CPm, choroid plexus mesenchyme: Bars, 50 µm.</p

GAD65/67 expression in the meninges and the presence of GABA beneath the meninges.

<p>(A) Double immunolabeling for GAD65/67 (Green) and Laminin (Red) in the E14.5 neocortical primordium. The signals for GAD65/67 were present along the basal lamina which is laminin-positive (arrow). (B) Double immunostaining for GAD65/67 (green) and pan-Zic proteins (Red) in the E14.5 neocortex. Most of the cells expressing GAD65/67 also express Zic proteins, which are the transcriptional factors working as the markers of the meningeal fibroblasts (arrowheads), although, to be noted, a few GAD65/67-positve cells do not express Zic proteins (arrow). A few Cajal-Retzius cells in the marginal zone (MZ) express Zic proteins (asterisks). (C) Immunostaining for GABA in the upper layers of developing neocortex. GABA signals could be observed at the upper edge of the E14.5 developing neocortex just beneath the meninge (arrows). GABA-containing neurons in the marginal zone and in the subplate are also visualized (several representatives are indicated by arrowheads). The counterstaining by 7-amino-actinomycin D (7-AAD) helps to visualize the contours and the density of the cells in the developing cortical layers. (D) The E14.5 sections stained for GAD65/67 and Rdh10, an RA-synthesizing enzyme. RA is known to be released from the meningeal fibroblasts <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056901#pone.0056901-Siegenthaler1" target="_blank">[11]</a>. The signals for both proteins were present in the meninges (arrows). Me, meninge; MZ, marginal zone; CP, cortical plate; SP, subplate. Bars, 50 µm.</p

GAD65 and GAD 67 expression in the E14.5 neocortical meninges.

<p>(A) The images for the section stained with DAPI (blue), anti-GAD65 antibody (red) and anti-GAD67 antibody (green). The stable signals for both isoforms of GAD were found in the meningeal region just above the upper edge of the neocortical primordium (arrows). The developing neurons in the neocortex, in the marginal zone (MZ) and the subplate (SP) also exhibited the faint signals for GAD67 (arrowheads). (B) The images for the negative control section stained without anti-GAD65 (NC for GAD65) and anti-GAD67 (NC for GAD67). Me, meninge, MZ, marginal zone; CP, cortical plate; SP, subplate. Bar, 50 µm.</p

Bestropin-1 (Best1), a GABA-permeable channel, is expressed in the meninges and the choroid plexus.

<p>(A) The faint signals for Best1 were ubiquitously detected in the cells in the E14.5 neocortical structures including GAD65/67-positive meninges. (B) The cells in the choroid plexus epithelium exhibited rather strong signals for Best1 on E14.5. Me, meninge; MZ, marginal zone; CP, cortical plate; SP, subplate, CPe, choroid plexus epithelium: CPm, choroid plexus mesenchyme: Bars, 50 µm.</p