Topic: Notch signaling pathway

Neuronal development can be severely impacted under pathological conditions, altering the maturation of neuronal cells. Allan Herndon Dudley Syndrome (AHDS) is a rare X-linked syndrome caused by a mutation in the SLC16A2 gene, which encodes the specific transporter (monocarboxylate transported 8, MCT8) of thyroid T3 hormone, reducing its presence in the central nervous system and leading to severe neurological impairment. We investigated the neuronal maturation in an in vitro organoid model of AHDS, in which the pathological condition was resembled by removing the T3 hormone from the culture m

Parkinson’s disease (PD) often results in hippocampal dysfunction, which leads to cognitive and emotional challenges and synaptic irregularities. This study attempted to assess behavioral anomalies and identify differentially expressed genes (DEGs) within the hippocampus of a hemiparkinsonian rat model to potentially uncover novel genetic candidates linked to hippocampal dysfunction. Striatal 6-hydroxydopamine (6-OHDA) infusions were performed unilaterally in the brains of adult SD rats, while dopaminergic impairments were verified in rats with 6-OHDA-lesioned striata. RNA sequencing and gene

The mammalian neocortex is populated by different neuronal and glia cell types. During development, excitatory projection neurons and certain glia lineages emerge from radial glial progenitors (RGP). Impairments in RGP progenitor behavior and lineage progression can affect neuron production and maturation, leading to cortical malformations such as micro- or macrocephaly. The Notch signaling pathway instructs stem cell self-renewal and differentiation in a variety of tissues, including the brain. The Notch1 receptor is expressed in RGPs during embryonic development and maintains the progenitor

Thyroid hormone (T3) plays a critical role during early brain and overall central nervous system (CNS) development, and it acts as a major regulator of CNS metabolism and mitochondrial activity.Mutations in the T3 specific receptor monocarboxylate transporter 8 (MCT8) lead to hypothyroidism condition as tough in the Allan Herndon Dudley Syndrome (AHDS), which is characterized by neurodevelopmental defects.We set up a brain organoid model resembling AHDS pathological scenario to study the neurodevelopmental defects and to screen new metabolic target to restore neuronal maturation.AHDS organoids

Adult neurogenesis in the subventricular zone (SVZ)-olfactory bulb (OB) pathway in the mammalian brain persists throughout life. An adaptor protein, thyroid hormone receptor interacting protein 6 (TRIP6) is required for self-renewal and proliferation and inhibits neuronal differentiation in neural stem cells (NSCs) of the SVZ. Notch signaling pathway is also necessary for NSC self-renewal and inhibits their neuronal differentiation. Furthermore, we find that TRIP6 activates the Notch signaling pathway. However, the mechanism underlying this process remains to be elucidated. Here, we performed