Sorafenib Alters Interstitial Proton and Sodium Levels in the Tumor Microenvironment: A H/Na Spectroscopic Imaging Study.

Cellular metabolism is inextricably linked to transmembrane levels of proton (H), sodium (Na), and potassium (K) ions. Although reduced sodium-potassium pump (Na-K ATPase) activity in tumors directly disturbs transmembrane Na and K levels, this dysfunction is a result of upregulated aerobic glycolysis generating excessive cytosolic H (and lactate) which are extruded to acidify the interstitial space. These oncogene-directed metabolic changes, affecting intracellular Na and H, can be further exacerbated by upregulation of ion exchangers/transporters.

Complexes of Iron(II), Cobalt(II), and Nickel(II) with DOTA-Tetraglycinate for pH and Temperature Imaging Using Hyperfine Shifts of an Amide Moiety.

Paramagnetic complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA) derivatives have shown potential for molecular imaging with magnetic resonance. DOTA-tetraglycinate (DOTA-4AmC) coordinated with lanthanide metal ions (Ln) demonstrates pH/temperature sensing with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) and Chemical Exchange Saturation Transfer (CEST), respectively, detecting nonexchangeable (e.g.

Transient impairment in microglial function causes sex-specific deficits in synaptic maturity and hippocampal function in mice exposed to early adversity.

Abnormal development and function of the hippocampus are two of the most consistent findings in humans and rodents exposed to early-life adversity (ELA), with males often being more affected than females. Using the limited bedding (LB) paradigm as a rodent model of ELA, we found that male adolescent mice that had been exposed to LB exhibit significant deficits in contextual fear conditioning and synaptic connectivity in the hippocampus, which are not observed in females. This is linked to altered developmental refinement of connectivity, with LB severely impairing microglial-mediated synaptic pruning in the hippocampus of male and female pups on postnatal day 17 (P17), but not in adolescent P33 mice when levels of synaptic engulfment by microglia are substantially lower.

mTOR inhibition enhances synaptic and mitochondrial function in Alzheimer's disease in an APOE genotype-dependent manner.

Apolipoprotein ε4 (APOE4) carriers develop brain metabolic dysfunctions decades before the onset of Alzheimer's disease (AD). A goal of the study is to identify if rapamycin, an inhibitor for the mammalian target of rapamycin (mTOR) inhibitor, would enhance synaptic and mitochondrial function in asymptomatic mice with human APOE4 gene (E4FAD) before they showed metabolic deficits. A second goal is to determine whether there may be genetic-dependent responses to rapamycin when compared to mice with human APOE3 alleles (E3FAD), a neutral AD genetic risk factor.