PLD3 is a neuronal lysosomal phospholipase D associated with β-amyloid plaques and cognitive function in Alzheimer's disease.

Phospholipase D3 (PLD3) is a protein of unclear function that structurally resembles other members of the phospholipase D superfamily. A coding variant in this gene confers increased risk for the development of Alzheimer's disease (AD), although the magnitude of this effect has been controversial. Because of the potential significance of this obscure protein, we undertook a study to observe its distribution in normal human brain and AD-affected brain, determine whether PLD3 is relevant to memory and cognition in sporadic AD, and to evaluate its molecular function.

Blockade of the 5-HT transporter contributes to the behavioural, neuronal and molecular effects of cocaine.

Background And Purpose: The psychostimulant cocaine induces complex molecular, cellular and behavioural responses as a consequence of inhibiting presynaptic dopamine, noradrenaline and 5-HT transporters. To elucidate 5-HT transporter (SERT)-specific contributions to cocaine action, we evaluated cocaine effects in the SERT Met172 knock-in mouse, which expresses a SERT coding substitution that eliminates high-affinity cocaine recognition.

Experimental Approach: We measured the effects of SERT Met172 on cocaine antagonism of 5-HT re-uptake using ex vivo synaptosome preparations and in vivo microdialysis.

Serotonin Transporter-Independent Actions of the Antidepressant Vortioxetine As Revealed Using the SERT Met172 Mouse.

Selective serotonin (5-HT, SERT) reuptake inhibitors (SSRIs) are the most commonly prescribed treatments for depression. However, they have delayed efficacy and can induce side-effects that can encourage discontinuation. Recently, agents have been developed, including vortioxetine (Trintellix), that augment SERT blockade with interactions at other targets.

Essential Contributions of Serotonin Transporter Inhibition to the Acute and Chronic Actions of Fluoxetine and Citalopram in the SERT Met172 Mouse.

Depression is a common mental illness and a leading cause of disability. The most widely prescribed antidepressant medications are serotonin (5-HT) selective reuptake inhibitors (SSRIs). Although there is much support for 5-HT transporter (SERT) antagonism as a basis of antidepressant efficacy, this evidence is indirect and other targets and mechanisms have been proposed.