Topic: α7 nicotinic acetylcholine receptors

Major depressive disorder (MDD) is a disabling psychiatric disorder and a major cause of global health burden, affecting approximately 280 million people. Traditional antidepressants primarily target the monoaminergic system, have significant side effects and leave approximately 40% of patients unresponsive to treatment. Ketamine (KET) is a fast-acting antidepressant that transiently inhibits N-methyl-d-aspartate receptors (NMDARs) to produce its antidepressant effects. KET is rapidly metabolised to hydroxynorketamine (HNK), which reduces depressive behaviour in rodents. HNK has been shown to

We investigated the impact of the human-specific protein CHRFAM7A (dupα7) on the function of α7 nicotinic acetylcholine receptors (nAChRs) in two different types of neurons: human induced pluripotent stem cell (hiPSC)-derived cortical neurons, and superior cervical ganglion (SCG) neurons, taken from transgenic mice expressing CHRFAM7A. The CHRFAM7A co-assembles with CHRNA7 but lacks a major part of the extracellular N-terminal ligand-binding domain. We assessed the function of homomeric and hybrid pentameric receptors with Fura-2 calcium imaging and three different α7-specific ligands: PNU2829

Cholinergic transmission is fundamental in memory mechanisms. Accordingly, the early degeneration of cholinergic fibers characterizing Alzheimer’s disease (AD) contributes to cognitive impairment, and mice lacking functional α7 nicotinic acetylcholine receptors (A7KO) develop an age-dependent AD-like phenotype, featuring increased levels of β-amyloid and phospho-tau, hippocampal plasticity deficits, neuronal loss and astrogliosis. Astrocytes, recognized partners of neurons in brain function, are characterized by a signaling system based on variations in intracellular Ca2+ concentration. Experi

Dysfunctional α7 nicotinic acetylcholine receptors (α7*nAChRs) and their genetic regulation have been associated with several neuropsychiatric diseases, including schizophrenia and Alzheimer’s disease (AD). Preclinical studies revealed that α7*nAChR ligands can improve executive function, commonly impaired across neuropsychiatric disorders. Yet, a translational gap prevents these findings from resulting into clinically effective treatments. To tackle this translational gap, we combine approaches such as transgenic rats, viral vector-mediated local gene expression, touchscreen-based behavioral