Neurodevelopment

…aspects across the age spectrum of neurodevelopment. The overarching goal is to extend our understanding of brain development and aging, including studies of the neurodevelopmental origins of later health and disease, by improving repeated measures across longer epochs of the lifespan to better predict outcomes at later ages

This Stanford symposium examines how molecular, cellular, and circuit-level advances in neurodevelopment shape understanding of behavior and health, with scientific talks, awards, and a poster session.

…body mass index (MBMI) impacts the neurodevelopment of the offspring in a region-specific way, possibly contributing to future obesity risk of the offspring. Our study investigates the associations between MBMI and neonatal global white matter integrity in 157 infant-mother dyads from FinnBrain Birth Cohort Study (www.finnbrain.fi). Following TBSS (Tract-based Spatial Statistics) skeletonization, associations between MBMI and mean diffusivity values were assessed using a voxel-wise non-

Aims: Autophagy is an evolutionary conserved process, that is very important in neurons. Neurons are post-mitotic cells which require a strict quality control mechanism to prevent accumulation of cellular debris and ensure nutrient and energy balance. Also synapses are key elements for healthy brain functioning. The synapses of neurons are highly dynamic, especially during early period of lifetimeand. Their rate increased during embryogenesis but subsequently unnecessary synapses are eliminated through a process called pruning modulated by autophagy. Many studies have shown that autophagy is a

…into the role of CETN3 in neurodevelopment. To delve deeper, we established a CETN3-KO H9 cell line and cultivated cerebral organoids using it. Mirroring the patient's phenotype, our cerebral organoids exhibited smaller sizes compared to the control group. Through immunofluorescence analysis, we observed that CETN3 deficiency interfered with neurodifferentiation and diminished the proliferation of neural stem cells. Additionally, our findings i

Juvenility (early life) is the crucial stage of neurodevelopment, as the alterations made during this time have been linked to long-term effects on cognition. The brain undergoes significant remodelling involving dendritic arborization, synaptogenesis and neuron proliferation within and between areas, particularly in the hippocampus, which plays a vital role in spatial memory processing. Spatial memory processing ability continues to develop alongside hippocampal maturation particularly before puberty. The N-methyl-d-aspartate (NMDA) type of glutamate receptor channel is essential for activity

Exposure to early life stress (ELS) can alter neurodevelopment and is implicated in disease risk in later life, including psychiatric and behavioural disorders. The developing brain is plastic, thus ELS may affect the development trajectory of the brain by altering processes such as neurogenesis. ELS is known to impair adult hippocampal neurogenesis, however, the brain regions, cell types and underlying molecular mechanisms altered by ELS during development are unclear. Using an optogenetic zebrafish model to elevate stress hormone levels, we analysed the effects of ELS on neurogenesis during

…protein that is important for neurodevelopment and hematopoiesis. Inherited or de novo mutations in the PHF6 gene cause Börjeson–Forssman–Lehmann syndrome (BFLS), a rare X-linked neurodevelopmental and endocrine disorder. Patients with BFLS present with intellectual disability (ID), which affects cognitive functioning and adaptive behaviour. To progress our understanding of how PHF6 mutations affect the nervous system in BFLS, we studied the impact of deletion of the Phf6 gene on brain development in conditional

Our environment is polluted with plastic waste, wherein the degradation leads to the formation of micro and nanoplastics (NPs). These plastic particles contaminate water, soil, air, and food, exposing humans throughout their lives. Although NPs are detected in the human body, such as in blood, feces, and placenta, their potential impact on human health remains poorly understood. Moreover, the developing brains of fetuses and children may be sensitive to these molecules, potentially leading to functional impairments and altered behavior. Our study investigates the impact of chronic, low-dose ex

…of epigenetic regulator, critical for neurodevelopment. Polycomb Repressive Complex 1 alters chromatin through the deposition of H2A ubiquitination(H2AK119ub1), in contrast, Polycomb repressive deubiquitinase (PR-DUB) complex removes H2AK119ub1. The antagonistic relationship maintains the appropriate balance of H2AK119ub within the cell to control gene expression. MBD5 plays an important role in stabilizing the PR-DUB. Mutations in MBD5 gene

Autism spectrum disorders (ASD) are associated with a high genetic heterogeneity, yet for many of the cases, the underlying molecular causes remain elusive. While several studies have elucidated some distinct patterns, fundamental questions persist: How do mutations dispersed across numerous genes lead to the development of a phenotypically similar disorder? Essentially, it remains largely unclear whether mutations in distinct genes lead to similar molecular and cellular states within the brain. Thus, it is important to identify molecular mechanisms responsible aiming to decipher points of con

Maternal immune activation (MIA) has been implicated in offspring neurodevelopmental and psychiatric disorders, although it is unknown to what extent MIA affects neurodevelopment in the general population, and whether effects differ by sex. The current study was set within FinnBrain, a prospective birth cohort study based in Turku, Finland. We examined the association between maternal prenatal C-reactive protein (CRP), a commonly used systemic inflammatory marker, and white matter fractional anisotropy (FA) and mean diffusivity (MD) in infant and 5-year-old offspring, using voxel-wise statisti

Maternal exposure to viruses and related immunogens can have deleterious effects on neurodevelopment and lead to an increased risk of several psychopathologies, such as schizophrenia. Alcohol use disorder is more prevalent among individuals diagnosed with schizophrenia. However, the mechanisms underlying this association remain unknown. Here, we exposed pregnant rats to the viral analogue poly IC and studied several features of alcohol use disorder in the offspring, including increased motivation, compulsivity, and preference for ethanol over an alternative reward (saccharine). Prior to these

Antidepressant treatment during pregnancy may endanger neurodevelopment of the offspring. Cellular parameters (hippocampal homeostasis) and physiological parameters (behavioral aspects) in the offspring of Mirtazapine treated and depressed mothers are not yet fully described. We evaluated changes in cellular calcium homeostasis (Fura2AM) and CaV1.2 expression, presence of mitochondrial superoxide radicals (MitoSOXTM) together with behavior of developing pups.As an experimental model of perinatal depression we used pre-gestational exposure to chronic unpredictable stress followed by Mirtazapine

…Neurodevelopment, in particular, depends on the timely integration of numerous molecular signals across cell types, thus deeply relying on metabolite signaling functions. Although measuring changes in metabolites is useful to describe the association between molecules and disorders, the molecular mechanisms through which these metabolites affect neurodevelopment remain un

The maternal gestational gut-microbiota has emerged as a potent modulator of neurodevelopment and increasing evidence links its alteration in the etiology of neurodevelopmental and neuropsychiatric conditions. The alar hypothalamus and the medial extended amygdala (EAme) are two key nodes of the social brain closely associated to these disorders. Notably, perinatal microbiota changes have been linked with morphological alterations in both brain regions. Moreover, microbiota-based interventions can modulate endogenous oxytocin levels in the hypothalamus. Hence, we hypothesized that the maternal

Neurodevelopment is a finely orchestrated process marked by the sequential, but intimately connected events of synapse formation, maturation, and the critical GABA shift, where GABAergic neurotransmission transitions from excitatory to inhibitory. The precise timing and intricate balance of excitatory and inhibitory signaling is crucial for establishing functional neural circuits, and when disrupted contribute to neurodevelopmental disorders (NDDs) like autism spectrum disorder (ASD) and epilepsy. Exploring human aspects of neuronal development and functioning face challenges due to limitation

There is growing recognition that host-associated microbiotas modulate intrinsic neurodevelopmental programs including those underlying human social behavior. Despite this awareness, the fundamental processes are generally not understood. We discovered that the zebrafish microbiota is necessary for normal social behavior. By examining neuronal correlates of behavior, we found that the microbiota restrains neurite complexity and targeting of key forebrain neurons within the social behavior circuitry. The microbiota is also necessary for both localization and molecular functions of forebrain mic

Focal Cortical Dysplasia (FCD) is the most common focal cortical malformation leading to intractable childhood focal epilepsy. In recent years, we and others have shown that FCD type II is caused by mosaic mutations in genes within the PI3K-AKT-mTOR-signaling pathway. Hyperactivation of the mTOR pathway accounts for neuropathological abnormalities and seizure occurrence in FCD. We further showed from human surgical FCDII tissue that epileptiform activity correlates with the density of mutated dysmorphic neurons, supporting their pro-epileptogenic role. The level of mosaicism, as defined by var

…in pediatric age group, where neurodevelopment may be irreversibly affected. Furthermore, although seizures are the most obvious manifestation of epilepsy, the cognitive and psychiatric dysfunction that often coexists in patients with this disorder has the potential to be equally disabling. Given these challenges,

In our everyday lives, we form connections and build up social networks that allow us to function successfully as individuals and as a society. Our social networks tend to include well-connected individuals who link us to other groups of people that we might otherwise have limited access to. In addition, we are more likely to befriend individuals who a) live nearby and b) have mutual friends. Interestingly, neurons tend to do the same…until development is perturbed. Just like social networks, neuronal networks require highly connected hubs to elicit efficient communication at minimal cost (you

…organic pollutants, on child neurodevelopment is now established, however our understanding of how these contaminants alter the human brain is very limited. To address this issue, more effort must be made to integrate brain imaging tools with epidemiological studies. In this seminar, I will be presenting EEG and MRI data collected in birth-cohort studies where impairments of cognitive and sensory functions were observed in association with prenatal exposure to mercury, lead, PCB or organ

The gut microbiota is emerging as an important modulator of brain function and behavior, as several recent discoveries reveal substantial effects of the microbiome on neurophysiology, neuroimmunity and animal behavior. Despite these findings supporting a “microbiome-gut-brain axis”, the molecular and cellular mechanisms that underlie interactions between the gut microbiota and brain remain poorly understood. To uncover these, the Hsiao laboratory is mining the human microbiota for microbial modulators of host neuroactive molecules, investigating the impact of microbiota-immune system interacti