Cotinine Plus Krill Oil Decreased Depressive Behavior, and Increased Astrocytes Survival in the Hippocampus of Mice Subjected to Restraint Stress

Abstract

Restraint stress (RS) is a condition affecting millions of people worldwide. The investigation of new therapies to alleviate the consequences of prolonged RS is much needed. Cotinine, a nicotine-derivative, has shown to prevent the decrease in cerebral synaptic density, working memory deficits, anxiety, and depressive-like behavior after prolonged restraint stress (RS) in mice. Furthermore, post-treatment with cotinine reduced the adverse effects of chronic RS on astrocyte survival and architecture. On the other hand, the nutritional supplement krill oil (KO), has shown to be beneficial in decreasing depressive-like behavior and oxidative stress. In this study, in the search for effective preventative treatments to be used in people subjected to reduced mobility, the effect of co-treatment with cotinine plus KO in mice subjected to prolonged RS was investigated. The results show that cotinine plus KO prevented the loss of astrocytes, the appearance of depressive-like behavior and cognitive impairment induced by RS. The use of the combination of cotinine plus KO was more effective than cotinine alone in preventing the depressive-like behavior in the restrained mice. The potential use of this combination to alleviate the psychological effects of reduced mobility is discussed.

Quinolinic Acid and Nuclear Factor Erythroid 2-Related Factor 2 in Depression: Role in Neuroprogression

“…In addition, immunohistochemical analysis of glial fibrillary acidic protein, an astrocytic marker, revealed a significantly reduced area covered by glial fibrillary acidic protein-positive cell bodies and processes in various brain regions of young patients with depression compared to a control group (Müller et al., 2001; Fatemi et al., 2004; Miguel-Hidalgo et al., 2010; Gittins and Harrison, 2011; Chandley et al., 2013). In a recent preclinical study by Mendoza et al. (2018), reduced number and complexity of astrocytes in the dentate gyrus region of the hippocampus was seen in a restraint stress mouse model of depression.…”

Advances in Technologies for Highly Active Omega-3 Fatty Acids from Krill Oil: Clinical Applications

“…Both fish oil and krill oil significantly reduced the immobility factors and increased the time of climbing and swimming, similar to imipramine, when compared with the control group. Both the fish oil and the krill oil led to decreased malondialdehyde and hydrogen peroxide levels, decreased catalase activity, increased glutathione peroxidase levels and increased superoxide dismutase activities and glutathione levels in hippocampal tissue [147].…”

Cholinergic Receptor Modulation as a Target for Preventing Dementia in Parkinson’s Disease

“…Different from nicotine, cotinine is safe and does not elicit addictive behaviors in mammals, including humans ( Yim and Hee, 1995 ; Hatsukami et al, 1997 ; Vainio et al, 1998 ; Zevin et al, 2000 ; Echeverria and Zeitlin, 2012 ; Thomopoulos et al, 2013 ). Cotinine has shown to protect astrocytes from the toxic effects of chronic and acute stress in vivo ( Alvarez-Ricartes et al, 2018 ; Mendoza et al, 2018 ; Oliveros-Matus et al, 2020 ) and to prevent the loss of presynaptic proteins such as synaptophysin in the PFC and hippocampus of mice subjected to chronic stress ( Grizzell et al, 2014 ; Grizzell and Echeverria, 2015 ). In addition, cotinine has shown to reduce the activation of macrophages ( Rehani et al, 2008 ) and be neuroprotective, reducing plaque deposition, tau hyperphosphorylation, and cognitive impairment while increasing the expression of the postsynaptic density protein 95 (PSD95) in transgenic AD mice overexpressing human Aβ peptides ( Terry et al, 2005 , 2012 , 2015 ; Echeverria et al, 2011 ; Echeverria and Zeitlin, 2012 ; Patel et al, 2014 ; Grizzell et al, 2017 ).…”