Genetic models of cleavage-reduced and soluble TREM2 reveal distinct effects on myelination and microglia function in the cuprizone model.

Triggering receptor expressed on myeloid cells 2 (TREM2) is a cell-surface immunoreceptor expressed on microglia, osteoclasts, dendritic cells and macrophages. Heterozygous loss-of-function mutations in TREM2, including mutations enhancing shedding form the cell surface, have been associated with myelin/neuronal loss and neuroinflammation in neurodegenerative diseases, such as Alzheimer`s disease and Frontotemporal Dementia. Using the cuprizone model, we investigated the involvement of soluble and cleavage-reduced TREM2 on central myelination processes in cleavage-reduced (TREM2-IPD), soluble-only (TREM2-sol), knockout (TREM2-KO) and wild-type (WT) mice.

Information-seeking across auditory scenes by an echolocating dolphin.

Dolphins gain information through echolocation, a publicly accessible sensory system in which dolphins produce clicks and process returning echoes, thereby both investigating and contributing to auditory scenes. How their knowledge of these scenes contributes to their echoic information-seeking is unclear. Here, we investigate their top-down cognitive processes in an echoic matching-to-sample task in which targets and auditory scenes vary in their decipherability and shift from being completely unfamiliar to familiar.

Sustained Trem2 stabilization accelerates microglia heterogeneity and Aβ pathology in a mouse model of Alzheimer's disease.

TREM2 is a transmembrane protein expressed exclusively in microglia in the brain that regulates inflammatory responses to pathological conditions. Proteolytic cleavage of membrane TREM2 affects microglial function and is associated with Alzheimer's disease, but the consequence of reduced TREM2 proteolytic cleavage has not been determined. Here, we generate a transgenic mouse model of reduced Trem2 shedding (Trem2-Ile-Pro-Asp [IPD]) through amino-acid substitution of an ADAM-protease recognition site.

Selectivity of (±)-citalopram at nicotinic acetylcholine receptors and different inhibitory mechanisms between habenular α3β4* and α9α10 subtypes.

The inhibitory activity of (±)-citalopram on human (h) α3β4, α4β2, and α7 nicotinic acetylcholine receptors (AChRs) was determined by Ca influx assays, whereas its effect on rat α9α10 and mouse habenular α3β4* AChRs by electrophysiological recordings. The Ca influx results clearly establish that (±)-citalopram inhibits (IC's in μM) hα3β4 AChRs (5.1 ± 1.

Alkaloids Purified from Inhibit the Human α3β4 Nicotinic Acetylcholine Receptor with Higher Potencies Compared with the Human α4β2 and α7 Subtypes.

The alkaloids aristoteline (), aristoquinoline (), and aristone () were purified from the leaves of the Maqui tree and chemically characterized by NMR spectroscopy. The pharmacological activity of these natural compounds was evaluated on human (h) α3β4, α4β2, and α7 nicotinic acetylcholine receptors (AChRs) by Ca influx measurements. The results suggest that these alkaloids do not have agonistic, but inhibitory, activity on each receptor subtype.