Functional Genomic Analysis of Amphetamine Sensitivity in .

Abuse of psychostimulants, including amphetamines (AMPHs), is a major public health problem with profound psychiatric, medical, and psychosocial complications. The actions of these drugs at the dopamine transporter (DAT) play a critical role in their therapeutic efficacy as well as their liability for abuse and dependence. To date, however, the mechanisms that mediate these actions are not well-understood, and therapeutic interventions for AMPH abuse have been limited.

Fumarate hydratase-deficient renal cell carcinoma cells respond to asparagine by activation of the unfolded protein response and stimulation of the hexosamine biosynthetic pathway.

Background: The loss-of-function mutation of fumarate hydratase (FH) is a driver of hereditary leiomyomatosis and renal cell carcinoma (HLRCC). Fumarate accumulation results in activation of stress-related mechanisms leading to upregulation of cell survival-related genes. To better understand how cells compensate for the loss of FH in HLRCC, we determined the amino acid nutrient requirements of the FH-deficient UOK262 cell line (UOK262) and its FH-repleted control (UOK262WT).

The effects of a HTR2B stop codon and testosterone on energy metabolism and beta cell function among antisocial Finnish males.

Herein, we examined insulin resistance (IR), insulin sensitivity (IS), beta cell activity, and glucose metabolism in subjects with antisocial personality disorder (ASPD), and whether the serotonin 2B (5-HT2B) receptor and testosterone have a role in energy metabolism. A cohort of subjects belonging to a founder population that included 98 ASPD males, aged 25-30, was divided into groups based on the presence of a heterozygous 5-HT2B receptor loss-of-function gene mutation (HTR2B Q20*; n = 9) or not (n = 89). Serum glucose and insulin levels were measured in a 5 h oral glucose tolerance test (75 g) and indices describing IR, IS, and beta cell activity were calculated.

Dose-dependent effects of ladostigil on microglial activation and cognition in aged rats.

Unlabelled: The current study determined the effects of chronic treatment of aging rats with ladostigil, a cholinesterase (ChE) and monoamine oxidase (MAO) inhibitor, at doses of 1 and 8.5 mg/kg/day, on novel object recognition (NOR) and reference memory in the Morris water maze (MWM). A dose of (1 mg/kg/day) did not inhibit ChE or MAO but prevented the loss of NOR and reference memory in the MWM that occurs at 20.

Anti-inflammatory effects of ladostigil and its metabolites in aged rat brain and in microglial cells.

Impaired mitochondrial function accompanied by microglial activation and the release of nitric oxide (NO) and pro-inflammatory cytokines has been reported in Alzheimer's disease, its prodromal phase of Mild Cognitive Impairment (MCI) and in aged rats. The present study showed that 6 months treatment of 16 month old rats with ladostigil (1 mg/kg/day), a novel drug designed for the treatment of MCI, prevented the development of spatial memory deficits at 22 months of age and significantly decreased the gene expression of IL-1β, IL-6, TNF-α and inducible nitric oxide synthase (iNOS) in the parietal cortex. It was also shown that concentrations ranging from 1nM-1 μM of ladostigil and three of its active metabolites inhibited the release of nitric oxide (NO) induced by lipopolysaccharide (LPS) from mouse microglial cells by up to 35-40 %.