Gut microbiota: A potential regulator of neurodevelopment

During childhood, our brain is exposed to a variety of environmental inputs that can sculpt synaptic connections and neuronal circuits, with subsequent influence on behavior and learning processes. Critical periods of neurodevelopment are windows of opportunity in which the neuronal circuits are extremely plastic and can be easily subjected to remodeling in response to experience. However, the brain is also more susceptible to aberrant stimuli that might lead to altered developmental trajectories. Intriguingly, postnatal brain development is paralleled by the maturation of the gut microbiota: the ecosystem of symbionts populating our gastro-intestinal tract. Recent discoveries have started to unveil an unexpected link between the gut microbiome and neurophysiological processes. Indeed, the commensal bacteria seem to be able to influence host behavioral outcome and neurochemistry through mechanisms which remain poorly understood. Remarkably, the efficacy of the gut flora action appears to be dependent on the timing during postnatal life at which the host gut microbes' signals reaches the brain, suggesting the fascinating possibility of critical periods for this microbiota-driven shaping of host neuronal functions and behavior. Therefore, to understand the importance of the intestinal ecosystem's impact on neuronal circuits functions and plasticity during development and the discovery of the involved molecular mechanisms, will pave the way to identify new and, hopefully, powerful microbiota-based therapeutic interventions for the treatment of neurodevelopmental and psychiatric diseases

The gut-brain connection: Exploring the influence of the gut microbiota on neuroplasticity and neurodevelopmental disorders

Neuroplasticity refers to the ability of brain circuits to reorganize and change the properties of the network, resulting in alterations in brain function and behavior. It is traditionally believed that neuroplasticity is influenced by external stimuli, learning, and experience. Intriguingly, there is new evidence suggesting that endogenous signals from the body's periphery may play a role. The gut microbiota, a diverse community of microorganisms living in harmony with their host, may be able to influence plasticity through its modulation of the gut-brain axis. Interestingly, the maturation of the gut microbiota coincides with critical periods of neurodevelopment, during which neural circuits are highly plastic and potentially vulnerable. As such, dysbiosis (an imbalance in the gut microbiota composition) during early life may contribute to the disruption of normal developmental trajectories, leading to neurodevelopmental disorders. This review aims to examine the ways in which the gut microbiota can affect neuroplasticity. It will also discuss recent research linking gastrointestinal issues and bacterial dysbiosis to various neurodevelopmental disorders and their potential impact on neurological outcomes

Mir-132/212 is required for maturation of binocular matching of orientation preference and depth perception

MicroRNAs (miRNAs) are known to mediate post-transcriptional gene regulation, but their role in postnatal brain development is still poorly explored. We show that the expression of many miRNAs is dramatically regulated during functional maturation of the mouse visual cortex with miR-132/212 family being one of the top upregulated miRNAs. Age-downregulated transcripts are significantly enriched in miR-132/miR-212 putative targets and in genes upregulated in miR-132/212 null mice. At a functional level, miR-132/212 deletion affects development of receptive fields of cortical neurons determining a specific impairment of binocular matching of orientation preference, but leaving orientation and direction selectivity unaltered. This deficit is associated with reduced depth perception in the visual cliff test. Deletion of miR-132/212 from forebrain excitatory neurons replicates the binocular matching deficits. Thus, miR-132/212 family shapes the age-dependent transcriptome of the visual cortex during a specific developmental window resulting in maturation of binocular cortical cells and depth perception

Electronic states and optical properties of GaAs/AlAs and GaAs/vacuum superlattices by the linear combination of bulk bands method

The linear combination of bulk bands method recently introduced by Wang, Franceschetti and Zunger [Phys. Rev. Lett.78, 2819 (1997)] is applied to a calculation of energy bands and optical constants of (GaAs)$_n$/(AlAs)$_n$ and (GaAs)$_n$/(vacuum)$_n$ (001) superlattices with n ranging from 4 to 20. Empirical pseudopotentials are used for the calculation of the bulk energy bands. Quantum-confined induced shifts of critical point energies are calculated and are found to be larger for the GaAs/vacuum system. The $E_1$ peak in the absorption spectra has a blue shift and splits into two peaks for decreasing superlattice period; the $E_2$ transition instead is found to be split for large-period GaAs/AlAs superlattices. The band contribution to linear birefringence of GaAs/AlAs superlattices is calculated and compared with recent experimental results of Sirenko et al. [Phys. Rev. B 60, 8253 (1999)]. The frequency-dependent part reproduces the observed increase with decreasing superlattice period, while the calculated zero-frequency birefringence does not account for the experimental results and points to the importance of local-field effects.Comment: 10 pages, 11 .eps figures, 1 tabl

Theoretical study of the insulating oxides and nitrides: SiO2, GeO2, Al2O3, Si3N4, and Ge3N4

An extensive theoretical study is performed for wide bandgap crystalline oxides and nitrides, namely, SiO_{2}, GeO_{2}, Al_{2}O_{3}, Si_{3}N_{4}, and Ge_{3}N_{4}. Their important polymorphs are considered which are for SiO_{2}: $\alpha$-quartz, $\alpha$- and $\beta$-cristobalite and stishovite, for GeO_{2}: $\alpha$-quartz, and rutile, for Al_{2}O_{3}: $\alpha$-phase, for Si_{3}N_{4} and Ge_{3}N_{4}: $\alpha$- and $\beta$-phases. This work constitutes a comprehensive account of both electronic structure and the elastic properties of these important insulating oxides and nitrides obtained with high accuracy based on density functional theory within the local density approximation. Two different norm-conserving \textit{ab initio} pseudopotentials have been tested which agree in all respects with the only exception arising for the elastic properties of rutile GeO_{2}. The agreement with experimental values, when available, are seen to be highly satisfactory. The uniformity and the well convergence of this approach enables an unbiased assessment of important physical parameters within each material and among different insulating oxide and nitrides. The computed static electric susceptibilities are observed to display a strong correlation with their mass densities. There is a marked discrepancy between the considered oxides and nitrides with the latter having sudden increase of density of states away from the respective band edges. This is expected to give rise to excessive carrier scattering which can practically preclude bulk impact ionization process in Si_{3}N_{4} and Ge_{3}N_{4}.Comment: Published version, 10 pages, 8 figure

miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity

miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP) induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity

Cocaine-mediated circadian reprogramming in the striatum through dopamine D2R and PPARγ activation

Substance abuse disorders are linked to alteration of circadian rhythms, although the molecular and neuronal pathways implicated have not been fully elucidated. Addictive drugs, such as cocaine, induce a rapid increase of dopamine levels in the brain. Here, we show that acute administration of cocaine triggers reprogramming in circadian gene expression in the striatum, an area involved in psychomotor and rewarding effects of drugs. This process involves the activation of peroxisome protein activator receptor gamma (PPARγ), a nuclear receptor involved in inflammatory responses. PPARγ reprogramming is altered in mice with cell-specific ablation of the dopamine D2 receptor (D2R) in the striatal medium spiny neurons (MSNs) (iMSN-D2RKO). Administration of a specific PPARγ agonist in iMSN-D2RKO mice elicits substantial rescue of cocaine-dependent control of circadian genes. These findings have potential implications for development of strategies to treat substance abuse disorders

Gut microbiota profile in CDKL5 deficiency disorder patients

: CDKL5 deficiency disorder (CDD) is a neurodevelopmental condition characterized by global developmental delay, early-onset seizures, intellectual disability, visual and motor impairments. Unlike Rett Syndrome (RTT), CDD lacks a clear regression period. Patients with CDD frequently encounter gastrointestinal (GI) disturbances and exhibit signs of subclinical immune dysregulation. However, the underlying causes of these conditions remain elusive. Emerging studies indicate a potential connection between neurological disorders and gut microbiota, an area completely unexplored in CDD. We conducted a pioneering study, analyzing fecal microbiota composition in individuals with CDD (n = 17) and their healthy relatives (n = 17). Notably, differences in intestinal bacterial diversity and composition were identified in CDD patients. In particular, at genus level, CDD microbial communities were characterized by an increase in the relative abundance of Clostridium_AQ, Eggerthella, Streptococcus, and Erysipelatoclostridium, and by a decrease in Eubacterium, Dorea, Odoribacter, Intestinomonas, and Gemmiger, pointing toward a dysbiotic profile. We further investigated microbiota changes based on the severity of GI issues, seizure frequency, sleep disorders, food intake type, impairment in neuro-behavioral features and ambulation capacity. Enrichment in Lachnoclostridium and Enterobacteriaceae was observed in the microbiota of patients with more severe GI symptoms, while Clostridiaceae, Peptostreptococcaceae, Coriobacteriaceae, Erysipelotrichaceae, Christensenellaceae, and Ruminococcaceae were enriched in patients experiencing daily epileptic seizures. Our findings suggest a potential connection between CDD, microbiota and symptom severity. This study marks the first exploration of the gut-microbiota-brain axis in subjects with CDD. It adds to the growing body of research emphasizing the role of the gut microbiota in neurodevelopmental disorders and opens doors to potential interventions that target intestinal microbes with the aim of improving the lives of patients with CDD

Measurement of the multiple-muon charge ratio in the MINOS Far Detector

The charge ratio, Rμ=Nμ+/Nμ−, for cosmogenic multiple-muon events observed at an underground depth of 2070 mwe has been measured using the magnetized MINOS Far Detector. The multiple-muon events, recorded nearly continuously from August 2003 until April 2012, comprise two independent data sets imaged with opposite magnetic field polarities, the comparison of which allows the systematic uncertainties of the measurement to be minimized. The multiple-muon charge ratio is determined to be Rμ=1.104±0.006(stat)+0.009−0.010(syst). This measurement complements previous determinations of single-muon and multiple-muon charge ratios at underground sites and serves to constrain models of cosmic-ray interactions at TeV energies

Search for Sterile Neutrinos Mixing with Muon Neutrinos in MINOS

We report results of a search for oscillations involving a light sterile neutrino over distances of 1.04 and 735 km in a νμ-dominated beam with a peak energy of 3 GeV. The data, from an exposure of 10.56 × 10^20 protons on target, are analyzed using a phenomenological model with one sterile neutrino. We constrain the mixing parameters θ24 and Δm41^2 and set limits on parameters of the four-dimensional Pontecorvo-Maki- Nakagawa-Sakata matrix, |Uμ4|2 and |Uτ4|2, under the assumption that mixing between νe and νs is negligible (|Ue4|^2 = 0). No evidence for νμ → νs transitions is found and we set a world-leading limit on θ24 for values of Δm41^2 ≲ 1 eV^2