Orthopedic Surgery Triggers Attention Deficits in a Delirium-Like Mouse Model.

Postoperative delirium is a frequent and debilitating complication, especially amongst high risk procedures such as orthopedic surgery, and its pathogenesis remains unclear. Inattention is often reported in the clinical diagnosis of delirium, however limited attempts have been made to study this cognitive domain in preclinical models. Here we implemented the 5-choice serial reaction time task (5-CSRTT) to evaluate attention in a clinically relevant mouse model following orthopedic surgery.

Neuroinflammation and Perioperative Neurocognitive Disorders.

Neuroinflammation has become a key hallmark of neurological complications including perioperative pathologies such as postoperative delirium and longer-lasting postoperative cognitive dysfunction. Dysregulated inflammation and neuronal injury are emerging from clinical studies as key features of perioperative neurocognitive disorders. These findings are paralleled by a growing body of preclinical investigations aimed at better understanding how surgery and anesthesia affect the central nervous system and possibly contribute to cognitive decline.

Modulation of neuroinflammation and memory dysfunction using percutaneous vagus nerve stimulation in mice.

Background: The vagus nerve is involved in regulating immunity and resolving inflammation. Current strategies aimed at modulating neuroinflammation and cognitive decline, in many cases, are limited and ineffective.

Objective: We sought to develop a minimally invasive, targeted, vagus nerve stimulation approach (pVNS), and we tested its efficacy with respect to microglial activation and amelioration of cognitive dysfunction following lipopolysaccharide (LPS) endotoxemia in mice.

A novel heterocyclic compound targeting the dopamine transporter improves performance in the radial arm maze and modulates dopamine receptors D1-D3.

A series of compounds targeting the dopamine transporter (DAT) haS been shown to improve memory performance most probably by re-uptake inhibition. Although specific DAT inhibitors are available, there is limited information about specificity, mechanism and in particular the effect on dopamine receptors. It was therefore the aim of the study to test the DAT inhibitor 4-(diphenyl-methanesulfinylmethyl)-2-methyl-thiazole (code: CE-111), synthetized in our laboratory for the specificity to target DAT, for the effects upon spatial memory and for induced dopamine receptor modulation.

A Novel Heterocyclic Compound CE-104 Enhances Spatial Working Memory in the Radial Arm Maze in Rats and Modulates the Dopaminergic System.

Various psychostimulants targeting monoamine neurotransmitter transporters (MATs) have been shown to rescue cognition in patients with neurological disorders and improve cognitive abilities in healthy subjects at low doses. Here, we examined the effects upon cognition of a chemically synthesized novel MAT inhibiting compound 2-(benzhydrylsulfinylmethyl)-4-methylthiazole (named as CE-104). The efficacy of CE-104 in blocking MAT [dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter] was determined using in vitro neurotransmitter uptake assay.

Frontal cortex and hippocampus neurotransmitter receptor complex level parallels spatial memory performance in the radial arm maze.

Several neurotransmitter receptors have been proposed to be involved in memory formation. However, information on receptor complexes (RCs) in the radial arm maze (RAM) is missing. It was therefore the aim of this study to determine major neurotransmitter RCs levels that are modulated by RAM training because receptors are known to work in homo-or heteromeric assemblies.

A cluster of protein kinases and phosphatases modulated in fetal Down syndrome (trisomy 21) brain.

Down syndrome (DS; trisomy 21) is the most frequent cause of mental retardation with major cognitive and behavioral deficits. Although a series of aberrant biochemical pathways has been reported, work on signaling proteins is limited. It was, therefore, the aim of the study to test a selection of protein kinases and phosphatases known to be essential for memory and learning mechanisms in fetal DS brain.

Hippocampal receptor complexes paralleling LTP reinforcement in the spatial memory holeboard test in the rat.

The current study was designed to examine learning-induced transformation of early-LTP into late-LTP. Recording electrodes were implanted into the dentate gyrus of the hippocampus in male rats and early-LTP was induced by weak tetanic stimulation of the medial perforant path. Dorsal right hippocampi were removed, membrane proteins were extracted, separated by blue-native gel electrophoresis with subsequent immunoblotting using brain receptor antibodies.

A hippocampal nicotinic acetylcholine alpha 7-containing receptor complex is linked to memory retrieval in the multiple-T-maze in C57BL/6j mice.

The link between the cholinergic and serotonergic system in cognitive function is well-documented. There is, however, limited information on spatial memory and this formed the rationale to carry out a study with the aim to show a specific link between nicotinic and serotonergic receptor complexes rather than the corresponding subunits, to spatial memory retrieval in a land maze. A total of 46 mice were used and divided into two groups, trained and untrained (yoked) in the multiple-T-Maze (MTM) and following training during the first four days, probe trials for memory retrieval were performed on days 8, 16 and 30.