Unusual Bioactive Compounds with Antioxidant Properties in Adjuvant Therapy Supporting Cognition Impairment in Age-Related Neurodegenerative Disorders

Cognitive function decline is strictly related to age, resulting in the loss of the ability to perform daily behaviors and is a fundamental clinical neurodegeneration symptom. It has been proven that an adequate diet, comprehensive nutrition, and a healthy lifestyle may significantly inhibit neurodegenerative processes, improving cognitive functions. Therefore, intensive research has been conducted on cognitive-enhancing treatment for many years, especially with substances of natural origin. There are several intervention programs aimed at improving cognitive functions in elderly adults. Cognitive functions depend on body weight, food consumed daily, the quality of the intestinal microflora, and the supplements used. The effectiveness in the prevention of dementia is particularly high before the onset of the first symptoms. The impact of diet and nutrition on age-associated cognitive decline is becoming a growing field as a vital factor that may be easily modified, and the effects may be observed on an ongoing basis. The paper presents a review of the latest preclinical and clinical studies on the influence of natural antioxidants on cognitive functions, with particular emphasis on neurodegenerative diseases. Nevertheless, despite the promising research results in animal models, the clinical application of natural compounds will only be possible after solving a few challenges.

Autophagy in DG engrams mediates Rac1-dependent forgetting during aging via microglia-mediated synapse elimination

Engrams are considered to be substrates for memory storage, and the functional dysregulation of the engrams leads to cognition impairment. However, the pathological changes of the engrams leading to forgetting, which typically involves a failure in memory retrieval, remains unclear. Here we found that the expression of autophagy protein 7 (Atg7) in dentate gyrus (DG) engrams was dramatically increased in aged mice, leading to the activation of surrounding microglia and impair retrieval of conditioned fear memory. Using transcriptomic and fluorescence in situ hybridization analyses, we demonstrated Toll-like receptor (TLR) pathway were upregulated in DG microglia by overexpressing ATG7 in DG engrams. TLR2/4 in the microglia mediates the excessive synapse elimination and impaired retrieval of fear memory induced by ATG7-depedent autophagy in DG engrams. The expression of Rac1, a Rho-GTPases which mediates active forgetting, was upregulated in aged engrams. Optogenetic activation of Rac1 in DG engrams promoted the expression of ATG7 and autophagy in the engrams, the activation of microglia, and thus impaired the retrieval of fear memory. Interference of the Atg7 expression in the engram and microglia activation prevented the impairment of fear memory retrieval induced by activation of Rac1 in DG engrams. Together, our findings revealed autophagy-dependent remodeling of DG engrams by microglia as a novel interference mechanism of memory retrieval.

Sex differences between serum total bilirubin levels and cognition in patients with schizophrenia

Background Cognitive deficits are common in patients with schizophrenia (SCZ). Abnormal serum total bilirubin (TBIL) levels have been involved in cognitive deficits associated with neuropsychiatric diseases such as mild cognitive impairment and subcortical ischemic vascular disease. However, this relationship has not yet been fully investigated in patients with SCZ. Therefore, the aim of this study was to investigate the association between the serum TBIL concentration and cognitive deficits in SCZ patients and to determine whether a sex difference exists in the association. Methods A total of 455 participants were eligible and included in this cross-sectional study. Cognition was evaluated using the Montreal Cognitive Assessment. Serum TBIL concentration was measured with an automatic biochemistry analyzer according to the routine protocol in the hospital medical laboratory. Results Serum TBIL levels were lower in the cognition impairment group than in the cognition normal group in male patients. In contrast, serum TBIL levels tended to be increased in the cognition impairment group in female patients, although the difference was not significant. Further stepwise multiple regression analysis stratified by sex showed that serum TBIL was independently and positively associated with cognitive function in male patients but not in female patients. Moreover, the association between serum TBIL level and cognitive function was also identified by the propensity score matching (PSM) method in male patients, but not in female patients. Conclusion These findings suggest that lower serum TBIL levels may be associated with cognitive impairment in male SCZ patients.

Dexmedetomidine Attenuates Hippocampal Damage and Improves Cognition by Up-Regulating Glyoxalase1 in APP/PS1 Mice

Background: Dexmedetomidine (DEX), an α2-adrenoceptor agonist, has been reported to possess neuroprotective effects against postoperative cognitive impairment. GLO-1 plays a key role in the pathogenesis of Alzheimer’s disease (AD). Here, the primary goal was to assess whether DEX affect GLO-1 and protect cognition impairment in APP/PS1 transgenic mice.Methods: After DEX was intraperitoneally injected in APP/PS1 mice, behavior was tested by Water Maze to illustrate whether DEX treatment has a significantly positive effect on ameliorating the cognition deficits in AD. We assessed the effect of DEX on the expression of GLO-1 and the production of other oxidative stress factors by ELISA and Western blot. To determine whether DEX play roles in the Aβ induced neuron apoptosis, flow cytometry was used.Results: DEX treatment significantly ameliorated cognition deficits in APP/PS1 mice. DEX increased GLO-1 expression and decreased MG activity in the hippocampus. In addition, DEX increased activity of SOD, GSH and reduced the activity of MDA. In vitro, DEX could protect the neuron apoptosis induced by Aβ. GLO-1 inhibitor could block the protective role of DEX.Conclusion: Taken together, our findings suggest that DEX prevents progression of AD-like pathology through upregulating GLO-1.