Nicotinamide reduces inflammation and oxidative stress via the cholinergic system in fructose-induced metabolic syndrome in rats.

AIMS: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have been associated with risk factors for metabolic syndrome (MetS). Our objective was to evaluate the effect of nicotinamide (NAM) on the activities, expression and protein content of cholinesterases in a MetS model. MAIN METHODS: MetS was induced in male rats administrating 40% fructose to the drinking water for 16 weeks. Additionally, from 5th week onward, the carbohydrate solution was replaced by NAM, at several concentrations for 5 h each morning for the next 12 weeks. In the 15th week, the glucose tolerance test was conducted, and blood pressure was measured. After the treatment period had concluded, the biochemical profile; oxidant stress; proinflammatory markers; and the activity, quantity and expression of cholinesterases were evaluated, and molecular docking analysis was performed. KEY FINDINGS: The MetS group showed anthropometric, hemodynamic and biochemical alterations and increased cholinesterase activity, inflammation and stress markers. In the liver, cholinesterase activity and mRNA, free fatty acid, tumor necrosis factor-alpha (TNF-α), and thiobarbituric acid-reactive substance (TBARS) levels were increased, while reduced glutathione (GSH) levels were decreased. NAM partially or totally decreased risk factors for MetS, markers of stress and inflammation, and the activity (serum and liver) and expression (liver) of cholinesterases. Molecular docking analysis showed that NAM has a greater affinity for cholinesterases than acetylcholine (ACh), suggesting NAM as an inhibitor of cholinesterases. SIGNIFICANCE: Supplementation with 40% fructose induced MetS, which increased the activity and expression of cholinesterases, oxidative stress and the inflammation. NAM attenuated these MetS-induced alterations and changes in cholinesterases.

5-HT1A receptor expression during memory formation.

RATIONALE: It has been reported that 5-HT(1A) receptors modulate learning and memory and diverse pharmacological and genetic evidence supports this notion. Nevertheless, there are few works about expression of these receptors during memory formation. OBJECTIVE: We aimed to determine 5-HT(1A) receptor expression in brain areas of untrained, passive, and autoshaping trained groups of rats. METHODS: Ex vivo receptor autoradiography using the ligand agonist [(3)H]8-hydroxy-2-[di-n-propylamino]tetralin] (8-OH-DPAT) was used. RESULTS: The trained group relative to untrained animals showed increases of 5-HT(1A) receptor expression in 14 brain areas, decrements in 7, and no changes in 12. Thus, in contrast to untrained rats, 5-HT(1A) receptor expression of autoshaping trained rats was augmented in the tubercule olfactory, septal nucleus, nucleus accumbens, caudate putamen, globus pallidus, striate, and parietal (1 and 2), temporal cortex (1 and 3), granular retrosplenial cortex (1), amygdala, and median and dorsal raphe nuclei. In contrast, in the latter group, receptors were decreased in the CA1 area, hypothalamus dorsal, frontal cortex (1 and 3), occipital cortex, cingulate cortex (1 and 2), and cuneiform nucleus. There were significant differences between passive vs trained groups, but not regarding untrained rats, in the lateral olfactory tract, dentate gyrus, CA3 area, ventromedial hypothalamic, lateral hypothalamus, preoptic medial, frontal cortex (2), granular retrosplenial cortex (2), entorhinal cortex (1 and 2), piriform cortex, and substantia nigra. CONCLUSIONS: These data suggest that upregulated, downregulated, and "silence" of 5-HT(1A) receptors in brain areas form part of neural circuits engaged in memory formation by demonstrating a high degree of specificity and memory mapping.