mTOR

Binge drinking (BD) is characterized by consuming at least 70 g for men and 56 g for women of pure alcohol within two hours. Clinical studies examining the impact of BD on memory in young adults have revealed impairments across various types of memory (episodic, visuospatial, working memory...), although the frequency of BD often varies among studies. Preclinical research indicates that BD leads to the degradation of glutamate-dependent synaptic plasticity, the cellular mechanism of learning and memory in the hippocampus, including the metabotropic form of glutamatergic long-term synaptic depr

Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that regulates fundamental cellular processes including growth control, autophagy and metabolism. mTOR constitutes the catalytic subunit of two signalling complexes: mTOR complex 1 (mTORC1) and 2 (mTORC2). Manipulating mTORC1 signalling in animal models has shown that this pathway has key roles in neurogenesis, and mTORC1 hyperactivation during neurodevelopment causes a group of disorders known as mTORopathies. mTORopathies typically involve brain malformations and neurological manifestations like epilepsy. One example is tube

We aimed to determine facial and hind paw allodynia in diabetic neuropathy model induced by streptozotocin (STZ) treatment and to determine the anti-allodynic effect of metformin treatment. STZ was intraperitoneally injected (150 mg/kg) to induce painful diabetic neuropathy, and 200 mg/kg of metformin was injected intraperitoneally on the 21st day. Both of the mechanical and cold sensitivity in facial and paw withdrawal region were quantified using von-Frey filaments and acetone solution, respectively. To test heat hyperalgesia, mice were placed into a plastic chamber with a glass floor and ra

The kinase Mammalian Target of Rapamycin (mTOR) plays a pivotal role in cellular metabolism and growth across diverse cell types. In neurons, mTOR assumes critical importance for both neuronal development and plasticity. Dysregulation of mTOR has been implicated in mTORopathies, including Tuberous Sclerosis Complex (TSC) and associated brain disorders like epilepsy. Despite its predominant cytoplasmic localization, several studies have reported the presence of mTOR in the nucleus. Through mass spectrometry analysis, we identified Brg1, the catalytic subunit of the BAF chromatin remodelling com

Endocrine disruptors (EDs) are ubiquitous compounds with the ability to interfere with endogenous hormones. Molecules identified as EDs are highly heterogeneous, but most of them are man-made chemicals, such as ethinyl estradiol (EE), medication, perfluorooctanesulfonic-acid (PFOS), surfactant, and diethyl-phthalate (DP), plasticizer. The constant exposure of the global population to these molecules can lead to an induction of toxic effects, especially on the central nervous system. Among the different mechanisms by which EDs could influence human health, of interest is the modulation of micro

Epileptogenesis, arising from alterations in synaptic strength, shares mechanistic and phenotypic parallels with memory formation. However, direct evidence supporting the existence of seizure memory remains scarce. We developed a novel conditioned seizure memory (CSM) paradigm, in which seizures and specific cues were paired. The CSM could be reliably retrieved, demonstrating a robust association. We also found that activation of cue-responding engram cells in hippocampus DG could create artificial CSM. After seizure memory retrieval, a protein synthesis-dependent reconsolidation process invol

The mTOR pathway is a pivotal cellular signaling pathway that impacts neuronal differentiation and function. Genetic disruptions leading to hyperactivation of the mTOR pathway, termed mTORopathies, represent rare genetic and systemic disorders that are associated with altered brain development and epilepsy. However, the precise mechanisms by which disrupted mTOR signaling affects neuronal network development and signaling remain poorly understood. Human induced pluripotent stem cells (iPSCs) and CRISPR/Cas9 genome editing, allowed the generation of a panel of isogenic iPSC lines carrying mutat

Chronic exercise is a powerful intervention that lowers the incidence of most age-related diseases while promoting healthy metabolism in humans. However, illness, injury or age prevent many humans from consistently exercising. Thus, identification of molecular targets that can mimic the benefits of exercise would be a valuable tool to improve health outcomes of humans with neurodegenerative or mitochondrial diseases, or those with enforced sedentary lifestyles. Using a novel exercise platform for Drosophila, we have identified octopaminergic neurons as a key subset of neurons that are critical

Malformations of cortical development (MCDs) result from alterations of one or combined developmental steps, including progenitors proliferation, neuronal migration and differentiation. They are important cause of childhood epilepsy and frequently associate cognitive deficits and behavioral alterations. Though the genetic basis of MCDs have known prominent progress during the past decade, including the identification of somatic, mosaic mutations responsible for focal MCDs, the pathophysiological mechanisms linking malformations to epileptogenesis remain elusive. In this seminar I will present

…II (FCDII) are caused by mutations in mTOR pathway genes leading to mTOR hyperactivity, focal malformations of cortical development (fMCD), and seizures in 80-90% of the patients. The current definitive treatments for epilepsy are surgical resection or treatment with everolimus, which inhibits mTOR activity (only approved for TSC). Because both options have severe limitations, there is a major need to better understand the mechanisms leading to seizures to improve life-long epilepsy treatment in TSC and FCDII. To investigate su