mTOR pathway

…Alterations in the mTOR pathway result in a spectrum of defects ranging from focal cortical dysplasia to hemimegalencephaly (HME). HME is a rare disorder, characterized by the enlargement of one hemisphere. To date, a detailed cellular and molecular understanding of the neuropathological und

Major Depressive Disorder (MDD) is a high-prevalence neuropsychiatric condition characterized by depressed mood and anxiety. The risk of suffering MDD is higher in people with obesity and metabolic dysregulation. We will evaluate the effect of a high-fat diet (HFD) and the impact of gender on behavioural, neurochemical and molecular markers associated with depression/anxiety.Male and female C57BL/6 mice, 6-weeks old, were given a 7-week HFD (60% fat). The behavioural tests performed were: open field test (OFT), novelty-suppressed feeding (NSF) test, sucrose preference test (SPT), and tail susp

…The mTOR pathway is a crucial pathway linking cellular metabolism to protein synthesis. The mTORC1 and 2 signaling complexes are composed of mTOR and distinct proteins, and while mTORC1 is regulated by AKT, mTORC2 is upstream of this enzyme and regulates phosphorylation of its serine 473 residue. Ribosomal protein S6 (RpS6)

…has revealed somatic mutations in mTOR pathway genes in up to 60% of FCDII-cases. Since available human FCDII samples reflect an advanced disease stage, the developmental origins and mechanisms, including the cell types affected by pathogenic mutations and their impact on cell-type-specific transcriptional programs, remain unknown. We aim t

…mutations in TSC1/2 genes, leading to mTOR pathway dysregulation and diverse cellular impacts. Individuals with TSC face severely heightened risk of autism spectrum disorder (ASD), highlighting a genetic link between the two conditions. To model ASD etiology in the context of TSC, we developed a new mouse model with Tsc2 knockout induced mid-gestation in all postmitotic, GABAergic neurons. As ASD and TSC both involve somatosensory processing challenges, we utilized our mouse model to assess how the mutation affects the cortical a

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

Epilepsy is one of the most common neurological diseases according to the World Health Organization (WHO) affecting around 70 million people worldwide [WHO]. Patients who suffer from epilepsy also suffer from a variety of neuro-psychiatric co-morbidities, which they can experience as crippling as the seizure condition itself. Adequate organization of cerebral white matter is utterly important for cognitive development. The failure of integration of neurologic function with cognition is reflected in neuro-psychiatric disease, such as autism spectrum disorder (ASD). However, in epilepsy we know

Epilepsy is one of the most common neurological diseases according to the World Health Organization (WHO) affecting around 70 million people worldwide [WHO]. Patients who suffer from epilepsy also suffer from a variety of neuro-psychiatric co-morbidities, which they can experience as crippling as the seizure condition itself. Adequate organization of cerebral white matter is utterly important for cognitive development. The failure of integration of neurologic function with cognition is reflected in neuro-psychiatric disease, such as autism spectrum disorder (ASD). However, in epilepsy we know

…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