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Omega-3 alleviates behavioral and molecular changes in a mouse model of stress-induced juvenile depression.
INTRODUCTION: Depression is increasingly diagnosed in adolescence, necessitating specific prevention and treatment methods. However, there is a lack of animal models mimicking juvenile depression. This study explores a novel model using ultrasound (US) stress in juvenile mice. METHODS: We employed the…
Nafamostat reduces systemic inflammation in TLR7-mediated virus-like illness.
BACKGROUND: The serine protease inhibitor nafamostat has been proposed as a treatment for COVID-19, by inhibiting TMPRSS2-mediated viral cell entry. Nafamostat has been shown to have other, immunomodulatory effects, which may be beneficial for treatment, however animal models of ssRNA virus infe…
Dysregulation of the NLRP3 Inflammasome and Promotion of Disease by IL-1β in a Murine Model of Sandhoff Disease.
Sandhoff disease (SD) is a progressive neurodegenerative lysosomal storage disorder characterized by GM2 ganglioside accumulation as a result of mutations in the HEXB gene, which encodes the β-subunit of the enzyme β-hexosaminidase. Lysosomal storage of GM2 triggers inflammation in the CNS an…
Pharmacological profiling of small molecule modulators of the TMEM16A channel and their implications for the control of artery and capillary function.
BACKGROUND AND PURPOSE: TMEM16A chloride channels constitute a depolarising mechanism in arterial smooth muscle cells (SMCs) and contractile cerebral pericytes. TMEM16A pharmacology is incompletely defined. We elucidated the mode of action and selectivity of a recently identified positive allost…
Impact of masticatory activity and rehabilitation on astrocyte morphology across the molecular layer of the dentate gyrus: Insights from the outer, medial, and inner sublayers and their relationship with spatial learning and memory.
The dentate gyrus plays a crucial role in learning and spatial memory, particularly in its middle third molecular layer, which receives the primary afferent input via the medial perforant path. Interestingly, changes in masticatory activity are described to affect this region with visible astrogliosis, release of pro-i…
Inhibiting IP6K1 confers atheroprotection by elevating circulating apolipoprotein A-I.
BACKGROUND AND AIMS: Atherosclerotic cardiovascular diseases are the leading cause of death. Apolipoprotein A-I (apoA-I) mediates cholesterol efflux to lower the risks of atherosclerosis. Elevating circulating apoA-I is an effective strategy for atheroprotection. However, the regulatory mechanisms of apoA-I…
Pramipexole for the Treatment of Depression: Efficacy and Mechanisms.
Dopaminergic mechanisms are a plausible treatment target for patients with clinical depression but are relatively underexplored in conventional antidepressant medications. There is continuing interest in the potential antidepressant effects of the dopamine receptor agonist, pramipexole, with data fr…
Diaphragm relaxation causes seizure-related apnoeas in chronic and acute seizure models in rats.
Ictal central apnoea is a feature of focal temporal seizures. It is implicated as a risk factor for sudden unexpected death in epilepsy (SUDEP). Here we study seizure-related apnoeas in two different models of experimental seizures, one chronic and one acute, in adult genetically-unmodified rats, to determine me…
Cholecystokinin-expressing neurons of the ventromedial hypothalamic nucleus control energy homeostasis.
The hypothalamus is the primary center of the brain that regulates energy homeostasis. The ventromedial hypothalamus (VMH) plays a central role in maintaining energy balance by regulating food intake, energy expenditure, and glucose levels. However, the cellular and molecular mechanisms underlying…
Offline hippocampal reactivation during dentate spikes supports flexible memory.
Stabilizing new memories requires coordinated neuronal spiking activity during sleep. Hippocampal sharp-wave ripples (SWRs) in the cornu ammonis (CA) region and dentate spikes (DSs) in the dentate gyrus (DG) are prime candidate network events for supporting this offline process. SWRs have been studied…
The annotation of GBA1 has been concealed by its protein-coding pseudogene GBAP1.
Mutations in GBA1 cause Gaucher disease and are the most important genetic risk factor for Parkinson's disease. However, analysis of transcription at this locus is complicated by its highly homologous pseudogene, GBAP1. We show that >50% of short RNA-sequencing reads mapping to GBA1 also map to GBAP…
Deletion of GBA in neurons, but not microglia, causes neurodegeneration in a Gaucher mouse model.
Gaucher disease, the most prevalent lysosomal storage disease, is caused by homozygous mutations at the GBA gene, responsible for encoding the enzyme glucocerebrosidase. Neuronopathic Gaucher disease is associated with microgliosis, astrogliosis, and neurodegeneration. However, the role that microglia,…
Compartmentalization proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation.
Endolysosomes (EL) are known for their role in regulating both intracellular trafficking and proteostasis. EL facilitate the elimination of damaged membranes, protein aggregates, membranous organelles and play an important role in calcium signaling. The specific role of EL in cardiac atrial fibrillation (AF) is not w…
Bayliss Starling Prize Lecture 2023: Neuropeptide-Y being 'unsympathetic' to the broken hearted.
William Bayliss and Ernest Starling are not only famous as pioneers in cardiovascular physiology, but also responsible for the discovery of the first hormone (from the Greek 'excite or arouse'), the intestinal signalling molecule and neuropeptide secretin in 1902. Our research group focuses on neuropeptides and…