“
“Type 2 diabetes (T2D) is one of the major risk factors
associated with Alzheimer’s disease (AD). Recent studies have found similarities in molecular mechanisms that underlie AS1842856 datasheet the respective degenerative developments in the two diseases. Pharmacological agents, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, which increase the level of glucagon-like peptide-1 (GLP-1) and ameliorate T2D, have become valuable candidates as disease modifying agents in the treatment of AD. In addition, endogenous GLP-1 levels decrease amyloid beta (A beta) peptide and tau phosphorylation in AD. The present study examines the efficacy of Saxagliptin, a DPP-4 inhibitor in a streptozotocin (STZ) induced rat model of AD. Three months following induction of AD by intracerebral administration of streptozotocin, animals were orally administered Saxagliptin (0.25, 0.5 and 1 mg/kg) for 60 days. The effect of the
DPP-4 inhibitor on hippocampal GLP-1 levels, A beta burden, tau phosphorylation, inflammatory markers and memory retention were evaluated. The results reveal an attenuation of A beta, tau phosphorylation and inflammatory markers and an improvement in hippocampal GLP-1 and memory retention following treatment. This remarkable therapeutic effect of Saxagliptin mediated through DPP-4 inhibition GW3965 mouse demonstrates a unique mechanism for A beta and tau clearance by increasing GLP-1 levels and reverses the behavioural deficits and pathology observed in AD. (C) 2013 Elsevier Ltd. All rights reserved.”
“There has been little investigation of the possible lasting adverse effects of gamma-hydroxybutyrate (GHB).
This study aims to study whether GHB produces residual adverse effects on memory and social behaviour in rats and lasting changes
Trichostatin A in brain monoamines and oxytocin-related gene expression.
Rats received daily intraperitoneal injections of GHB (500 mg/kg), methylenedioxymethamphetamine (MDMA; 5 mg/kg) or their combination (GHB/MDMA) over ten consecutive days. Locomotor activity and body weight were assessed during the dosing period and withdrawal-related anxiety was assessed 24 h after drug cessation. After a washout of 4 weeks, rats were tested on the emergence, social interaction, and object recognition tasks over a 2-week period. Monoamine levels in cortex and striatum, and hypothalamic oxytocin and oxytocin receptor mRNA, were then assessed.
MDMA and GHB/MDMA caused modest sensitization of locomotor activity over time, while sedative effects of GHB diminished with repeated exposure. GHB-treated rats showed reduced social interaction 24 h after the final dose, indicating GHB withdrawal-induced anxiety. All drug-treated groups displayed residual deficits in social interaction and object recognition. No changes in monoamine levels were detected 8 weeks post-drug. However, MDMA pre-exposure increased hypothalamic oxytocin mRNA while GHB pre-exposure upregulated oxytocin receptor mRNA.