Knock-Out of IKKepsilon Ameliorates Atherosclerosis and Fatty Liver Disease by Alterations of Lipid Metabolism in the PCSK9 Model in Mice.

The inhibitor-kappaB kinase epsilon (IKKε) represents a non-canonical IκB kinase that modulates NF-κB activity and interferon I responses. Inhibition of this pathway has been linked with atherosclerosis and metabolic dysfunction-associated steatotic liver disease (MASLD), yet the results are contradictory. In this study, we employed a combined model of hepatic PCSK9 overexpression and a high-fat diet for 16 weeks to induce atherosclerosis and liver steatosis.

Layer-specific changes of KCC2 and NKCC1 in the mouse dentate gyrus after entorhinal denervation.

The cation-chloride cotransporters KCC2 and NKCC1 regulate the intracellular Cl concentration and cell volume of neurons and/or glia. The Cl extruder KCC2 is expressed at higher levels than the Cl transporter NKCC1 in mature compared to immature neurons, accounting for the developmental shift from high to low Cl concentration and from depolarizing to hyperpolarizing currents through GABA-A receptors. Previous studies have shown that KCC2 expression is downregulated following central nervous system injury, returning neurons to a more excitable state, which can be pathological or adaptive.

Precise measurement of gene expression changes in mouse brain areas denervated by injury.

Quantitative PCR (qPCR) is a widely used method to study gene expression changes following brain injury. The accuracy of this method depends on the tissue harvested, the time course analyzed and, in particular on the choice of appropriate internal controls, i.e.

Granule Cell Ensembles in Mouse Dentate Gyrus Rapidly Upregulate the Plasticity-Related Protein Synaptopodin after Exploration Behavior.

The plasticity-related protein Synaptopodin (SP) has been implicated in neuronal plasticity. SP is targeted to dendritic spines and the axon initial segment, where it organizes the endoplasmic reticulum (ER) into the spine apparatus and the cisternal organelle, respectively. Here, we report an inducible third localization of SP in the somata of activated granule cell ensembles in mouse dentate gyrus.

Region-Specific Differences in Amyloid Precursor Protein Expression in the Mouse Hippocampus.

The physiological role of amyloid precursor protein (APP) has been extensively investigated in the rodent hippocampus. Evidence suggests that APP plays a role in synaptic plasticity, dendritic and spine morphogenesis, neuroprotection and-at the behavioral level-hippocampus-dependent forms of learning and memory. Intriguingly, however, studies focusing on the role of APP in synaptic plasticity have reported diverging results and considerable differences in effect size between the dentate gyrus (DG) and area CA1 of the mouse hippocampus.

Extracellular vesicle-mediated transfer of genetic information between the hematopoietic system and the brain in response to inflammation.

Mechanisms behind how the immune system signals to the brain in response to systemic inflammation are not fully understood. Transgenic mice expressing Cre recombinase specifically in the hematopoietic lineage in a Cre reporter background display recombination and marker gene expression in Purkinje neurons. Here we show that reportergene expression in neurons is caused by intercellular transfer of functional Cre recombinase messenger RNA from immune cells into neurons in the absence of cell fusion.

Phosphodiesterase 2A localized in the spinal cord contributes to inflammatory pain processing.

Background: Phosphodiesterase 2A (PDE2A) is an evolutionarily conserved enzyme that catalyzes the degradation of the cyclic nucleotides, cyclic adenosine monophosphate, and/or cyclic guanosine monophosphate. Recent studies reported the expression of PDE2A in the dorsal horn of the spinal cord, pointing to a potential contribution to the processing of pain. However, the functions of PDE2A in spinal pain processing in vivo remained elusive.

Upregulation of APP, ADAM10 and ADAM17 in the denervated mouse dentate gyrus.

The disintegrin and metalloproteinases ADAM10 and ADAM17 are regarded as the most important α-secretases involved in the physiological processing of amyloid precursor protein (APP) in brain. Since it has been suggested that processing of APP by α-secretases could be involved in the reorganization of the brain following injury, we studied mRNA expression of the two α-secretases Adam10 and Adam17, the ß-secretase Bace1, and the App-gene family (App, Aplp1, Aplp2) in the dentate gyrus of the mouse following entorhinal denervation. Using laser microdissection, tissue was harvested from the outer molecular layer and the granule cell layer of the denervated dentate gyrus.

Regulation of the spatial code for BDNF mRNA isoforms in the rat hippocampus following pilocarpine-treatment: a systematic analysis using laser microdissection and quantitative real-time PCR.

Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival, differentiation, and plasticity and is one of those genes that generate multiple mRNAs with different alternatively spliced 5'UTRs. The functional significance of many BDNF transcripts, each producing the same protein, is emerging. On the basis of the analysis of the four most abundant brain BDNF transcripts, we recently proposed the "spatial code hypothesis of BDNF splice variants" according to which the BDNF transcripts, through their differential subcellular localization in soma or dendrites, represent a mechanism to synthesize the protein at distinct locations and produce local effects.