Topic: bumetanide

Infantile neuronal ceroid lipofuscinosis (INCL) is a rare lysosomal storage disorder caused by mutations in the Cln1 gene, which encodes the Palmitoyl-Protein Thioesterase 1 (PPT1) enzyme. Like human patients, mutant mice exhibit defective autophagy, leading to widespread neuronal death accompanied by symptoms such as epilepsy, retinal and cortical degeneration, and premature death (Gupta, 2001). However, the precise mechanism linking Cln1 mutation to hyperexcitability and altered brain processing remains poorly understood. First, video-recordings in an open field arena demonstrated that CLN1

Exaggerated responses to sensory stimuli is a hallmark of Fragile X syndrome (FXS), contributes to, inattention, anxiety, and learning challenges. Such sensory hypersensitivity are recapitulated in the Fmr1 knockout (KO). Recent studies in Fmr1 KO mice have demonstrated differences in GABAergic inhibition, including activity of cortical interneurons as well as a delayed switch in the polarity of GABA signaling during development. Previously, we found that administration of bumetanide to block the chloride (Cl-) transporter NKCC1, could rescue synaptic circuit phenotypes in primary somatosensor

Cajal-Retzius neurons (CRNs) are among the first-born neurons in the neocortex and are critically involved in cortical layering during their transient lifetime. The molecular mechanisms behind early death of CRNs are still unclear but apoptosis is regulated by neuronal activity. During early development, CRNs are embedded into immature circuits where they mostly receive GABAergic inputs. Through immunohistochemistry and high-resolution confocal imaging, we quantified GABAergic synapse localizations across cortical layers during development in early postnatal mice and compared the GABAergic pro