Global loss of acetylcholinesterase activity with mitochondrial complexes inhibition and inflammation in brain of hypercholesterolemic mice

Abstract

There exists an intricate relationship between hypercholesterolemia (elevated plasma cholesterol) and brain functions. The present study aims to understand the impact of hypercholesterolemia on pathological consequences in mouse brain. A chronic mouse model of hypercholesterolemia was induced by giving high-cholesterol diet for 12 weeks. The hypercholesterolemic mice developed cognitive impairment as evident from object recognition memory test. Cholesterol accumulation was observed in four discrete brain regions, such as cortex, striatum, hippocampus and substantia nigra along with significantly damaged blood-brain barrier by hypercholesterolemia. The crucial finding is the loss of acetylcholinesterase activity with mitochondrial dysfunction globally in the brain of hypercholesterolemic mice, which is related to the levels of cholesterol. Moreover, the levels of hydroxyl radical were elevated in the regions of brain where the activity of mitochondrial complexes was found to be reduced. Intriguingly, elevations of inflammatory stress markers in the cholesterol-rich brain regions were observed. As cognitive impairment, diminished brain acetylcholinesterase activity, mitochondrial dysfunctions, and inflammation are the prima facie pathologies of neurodegenerative diseases, the findings impose hypercholesterolemia as potential risk factor towards brain dysfunction.

Neurological sequel of chronic kidney disease: From diminished Acetylcholinesterase activity to mitochondrial dysfunctions, oxidative stress and inflammation in mice brain

“…Object location memory (OLM) and object recognition memory (ORM) tests of the experimental animals were performed to assess their cognitive functions. The tests were performed following Paul and Borah 32 . For performing OLM test, two identical objects were placed 7 cm apart from each other in a chamber of 30 cm × 23 cm dimensions.…”

“…AChE activity was estimated from brain tissue sections, following Paul and Borah 32 . Briefly, mice were anaesthetised, and perfused with 30 mL each of ice-cold phosphate buffered saline (PBS, 0.1 M, pH 7.4) and 10% v/v glycerol.…”

Anti-Alzheimer Activity of Tacrine Loaded Methoxypoly (Ethylene Glycol) Poly (Caprolactone) Nanoparticles

“…If there should be an occurrence of midbrain, there were no distinctions in complete AChE behavior between the two gatherings; however, dissolvable AChE action was essentially high in the took care of vehicle-infused assemble [24]. The elevated cholesterol eating routine gathering of mice showed impressively impeded LTM contrasted with the control animals which were clear from the segregation list score of question acknowledgment memory tests [25]. The catalysts hindrance might be fundamentally influenced by pH, in the irreversible no not as much as the reversible case.…”

Towards a comprehensive understanding of the contributions of mitochondrial dysfunction and oxidative stress in the pathogenesis and pathophysiology of Huntington's disease

“…Inhibition of mitochondrial complexes (I and II) activity has been observed in the cortex of genetic models of hypercholesterolemia (de Oliveira et al, , ). Increased OS in the brain regions of hypercholesterolemic mice have been observed (Paul & Borah, ) and several lines of evidence indicate that hypercholesterolemia induces OS (de Oliveira et al, , ; Nelson & Alkon, ; Pappolla et al, ). Notably, research indicates that cholesterol‐induced OS plays an essential role in HD pathology (Kreilaus et al, ).…”

“…Importantly, mHTT‐induced PGC1α dysregulation and MtD play a role in the reduction of acetyl‐CoA and ATP synthesis, contributing to cholesterol dysregulation in HD pathology (Leoni & Caccia, ). Research on mice has found the loss of mitochondrial complexes activity in the whole brain of hypercholesterolemic mice contributing to cognitive impairment (Paul & Borah, ). Inhibition of mitochondrial complexes (I and II) activity has been observed in the cortex of genetic models of hypercholesterolemia (de Oliveira et al, , ).…”