In vivo and in vitro effects of fructose on rat brain acetylcholinesterase activity: an ontogenetic study

Abstract

Increased fructose concentrations are the biochemical hallmark of fructosemia, a group of inherited disorders on the metabolic pathway of this sugar. The main clinical findings observed in patients affected by fructosemia include neurological abnormalities with developmental delay, whose pathophysiology is still undefined. In the present work we investigated the in vitro and in vivo effects of fructose on acetylcholinesterase (AchE) activity in brain structures of developing rats. For the in vitro experiments, fructose was added at increasing concentrations to the incubation medium. It was observed that fructose provoked an inhibition of acetylcholinesterase activity in cerebral cortex of 30-day-old-rats, even at low concentrations (0.1 mM). For the in vivo experiments, rats were killed 1 h after a single fructose administration (5 μmol/g). Control group received the same volume of saline solution. We found that AchE activity was increased in cerebral cortex of 30-and 60-day-old rats receiving fructose administration. Finally, we observed that AchE activity was unaffected by acute fructose administration in cerebral cortex, striatum or hippocampus of 15-and 90-day-old rats. The present data suggest that a disruption in cholinergic homeostasis may be involved in the pathophysiology of brain damage observed in young patients affected by fructosemia.

Depression and Cognitive Impairment—Extrahepatic Manifestations of NAFLD and NASH

“…Their findings suggested an acceleration in neurodegeneration and in Aβ plaque formation after HFD-induced acute inflammation and NAFLD development [30]. The fact that HFD and fructose-rich diets may quicken AD cognitive decline has also been confirmed in recent experimental studies [32][33][34].…”

“…Moreover, an excessive consumption of fructose, a monosaccharide mainly used as sweetening agent in soft drinks, in addition to systemic metabolic alterations, was able to induce oxidative stress, thereby causing lipid peroxidation and protein nitrosylation in the hippocampus and reducing the expression of synaptic proteins, leading to impaired synaptic function, thus affecting learning and memory in a long-lived animal model [ 48 ]. Accordingly, many reports investigating the association between obesity and cognitive impairment have reported that the consumption of high-fat and high-sugar diet is able to increase oxidative stress, inflammation, and AChE activity, leading to cerebrovascular changes and neuronal loss in the hippocampus, disrupt myelination and axonal transmission, and decrease of dopamine (DA) and serotonin (5-HT) in the hippocampus, two of the key neurotransmitters involved in learning and memory processes [ 33 , 34 , 49 , 50 ].…”