Topic: RNAseq

Leucine rich repeat transmembrane proteins (LRRMTs) are synaptic adhesion proteins able to influence synapse development and function. LRRTM4, one of the 4 members of this protein group, is able to induce presynaptic differentiation and plays a significant role in excitatory synapse development. LRRTM4 polymorphisms have been linked to multiple neuropsychiatric diseases, but the underlying mechanisms are currently unclear. Therefore, we aimed to better understand the role of this gene for brain function by combining a battery of behavioural assays with transcriptomic and metabolomic analysis u

The ability to remember and recognize familiar conspecifics is essential for social interaction. Social memory disorders affect normal social interaction. Engram neurons relate to social memory formation with unclear mechanisms. G protein-coupled receptor 50 (GPR50) is an X chromosome-associated orphan receptor and is highly expressed in neurons. In this study, using social disorders mouse model establishing, chemical modulation, electrophysiology, and RNAseq, we herein report a novel role of GPR50 in social memory formation via activating engram neurons. Our results demonstrate that GPR50 upr

Dravet syndrome (DS) is a rare form of epilepsy caused by loss-of-function mutations of the voltage-gated sodium channel NaV1.1. The proposed disease mechanism suggests that these mutations compromise the ability of inhibitory interneurons to regulate network activity, leading to seizure events. However, standard treatments aimed at restoring inhibition have very limited efficacy, suggesting a potential role for excitatory neurons in DS pathogenesis. To explore this, we generated excitatory and inhibitory neurons from control and Dravet hiPSCs and combined them at physiological ratios into i

Over 400 mutations have been identified as contributors to inborn errors of immunity (IEI). Although IEI patients are primarily treated for immunodeficiency, an increasing number of reports have suggested that neurodevelopmental deficits (NDDs) may also be a co-morbidity of IEI. However, the mechanisms by which typically immune mutations could potentially increase NDD risk are currently unknown. To investigate this, we explored whether an overlap between IEI and NDD susceptibility genes existed, and evaluated which pathways were affected by these genes. Data mining of the HGMD and the IUIS gen

Cerebral function depends on the transmission of chemical signals between neuronal elements at synapses. Over the last two decades, accumulating data have shown that this fundamental process is regulated by astrocytes. Among other functions, astrocytes participate in the clearance of ions and neurotransmitters. In addition, these glial cells release gliotransmitters to regulate synaptic functions such as basal synaptic transmission and long-term synaptic plasticity. Clearance and gliotransmission are not the only ways through which astrocytes influence neuronal communication. One interesting b

Recent studies have shown that molecular programming by basic helix-loop-helix (bHLH) proteins can reactivate wiring in adult neurons. Meanwhile circuit analyses in these studies demonstrated functional circuit formation, the underlying molecular mechanisms remain elusive. Here, we used RNAseq, mass-spectrometry, and immunohistochemistry to investigate the transcriptomic and proteomic consequences of Id2 (a regulator of bHLH transcription factors) and Ascl4 (a bHLH transcription factor)-induced wiring in adult hippocampal granule cells, which lead to the formation of mainly feedback and feedfo

Axonal protein synthesis seems to play an important role in retinal ganglion cells (RGCs) axon guidance because axonal mRNAs could be locally translated “on demand” during axonal navigation. During embryonic development, RGC axons project to the brain and have to decide whether or not to cross the midline at the level of the optic chiasm. There are two types of RGCs, the contralateral ones (cRGCs) that respond to attractive cues; and the ipsilateral ones (iRGCs), that respond to repulsive cues. Although RGCs growth cones have a very fast dynamic behavior in response to environmental stimuli, k

Unhealthy nutrition, such as that characterized by a westernized style, can lead to metabolic syndrome (MetS), a cluster of cardio-metabolic risk factors associated with increased incidence of cognitive dysfunction, reducing the quality of life during aging. By contrast, regular consumption of nutraceuticals may promote brain and metabolic health, with limited side effects. We investigated whether oral administration of the polyphenol rosmarinic acid (RA, 500mg/kg) might protect aged male and female C57BL/6N mice from cognitive decline and metabolic derangement upon western diet (WD, 5.28 kcal