Does activation of oxytocinergic reward circuits postpone the decline of the aging brain?

Oxytocin supports reproduction by promoting sexual- and nursing behavior. Moreover, it stimulates reproductive organs by different avenues. Oxytocin is released to the blood from terminals of oxytocinergic neurons which project from the hypothalamus to the pituitary gland. Concomitantly, the dendrites of these neurons discharge oxytocin into neighboring areas of the hypothalamus. At this location it affects other neuroendocrine systems by autocrine and paracrine mechanisms. Moreover, sensory processing, affective functions, and reward circuits are influenced by oxytocinergic neurons that reach different sites in the brain. In addition to its facilitating impact on various aspects of reproduction, oxytocin is revealed to possess significant anti-inflammatory, restoring, and tranquilizing properties. This has been demonstrated both in many in-vivo and in-vitro studies. The oxytocin system may therefore have the capacity to alleviate detrimental physiological- and mental stress reactions. Thus, high levels of endogenous oxytocin may counteract inadequate inflammation and malfunctioning of neurons and supportive cells in the brain. A persistent low-grade inflammation increasing with age-referred to as inflammaging-may lead to a cognitive decline but may also predispose to neurodegenerative diseases such as Alzheimer's and Parkinson. Interestingly, animal studies indicate that age-related destructive processes in the body can be postponed by techniques that preserve immune- and stem cell functions in the hypothalamus. It is argued in this article that sexual activity-by its stimulating impact on the oxytocinergic activity in many regions of the brain-has the capacity to delay the onset of age-related cerebral decay. This may also postpone frailty and age-associated diseases in the body. Finally, oxytocin possesses neuroplastic properties that may be applied to expand sexual reward. The release of oxytocin may therefore be further potentiated by learning processes that involves oxytocin itself. It may therefore be profitable to raise the consciousness about the potential health benefits of sexual activity particularly among the seniors.

Oxytocin Release: A Remedy for Cerebral Inflammaging.

Oxytocin facilitates reproduction both by physiological and behavioral mechanisms. Oxytocinergic neurons emerging from the hypothalamus release oxytocin from the pituitary gland to the blood by axonal discharge to regulate reproductive organs. However, at the same time, oxytocin is secreted into neighboring areas of the hypothalamus from the dendrites of these neurons. Here, the peptide acts by autocrine and paracrine mechanisms to influence other neuroendocrine systems. Furthermore, oxytocinergic neurons project to many different locations in the brain, where they affect sensory processing, affective functions, and reward. Additional to its regulatory role, significant anti-inflammatory and restoring effects of oxytocin have been reported from many invivo and in-vitro studies. The pervasive property of the oxytocin system may enable it generally to dampen stress reactions both peripherally and centrally, and protect neurons and supportive cells from inadequate inflammation and malfunctioning. Animal experiments have documented the importance of preserving immune- and stem cell functions in the hypothalamus to impede age-related destructive processes of the body. Sexual reward has a profound stimulating impact on the oxytocinergic activity, and the present article therefore presents the hypothesis that frequent sexual activity and gratigying social experiance may postpone the onset of frailty and age-associated diseases by neural protection from the bursts of oxytocin. Furthermore, suggestions are given how the neuroplastic properties of oxytocin may be utilized to enhance sexual reward by learning processes in order to further reinforce the release of this peptide.

Can intravenous oxytocin infusion counteract hyperinflammation in COVID-19 infected patients?

OBJECTIVES: Based on its well-documented anti-inflammatory and restorative properties we propose trials with the natural hormone oxytocin for treatment of hospitalised Covid-19 patients. METHODS: We searched for, retrieved, and commented on specific literature regarding multiple functions of oxytocin with a special focus on its modulation of inflammatory, immune, and restorative functions. RESULTS: Available data gathered in animals and humans support the anti-inflammatory properties of oxytocin. The multiple anti-inflammatory effects of oxytocin have been demonstrated in vitro and in vivo in various animal models and also in humans in response to intravenous infusion of oxytocin. Furthermore, oxytocin has been documented to activate several types of protective and restorative mechanisms and to exert positive effects on the immune system. CONCLUSIONS: In addition, to being anti-inflammatory, it may be hypothesised, that oxytocin may be less suppressive on adaptive immune systems, as compared with glucocorticoids. Finally, by its restorative effects coupled with its anti-stress and healing properties, oxytocin may shorten the recovery period of the Covid-19 patients.

Oxytocin may have a therapeutical potential against cardiovascular disease. Possible pharmaceutical and behavioral approaches.

Based on the ancient role of oxytocin and its homologues as amplifiers of reproduction we argue for an evolutionary coupling of oxytocin to signaling pathway which support restorative mechanisms of cells and tissue. In particular, the survival and function of different categories of stem cells and primordial cells are enhanced by mitogen-activated protein kinase (MAPK) pathways. Furthermore, oxytocin stimulates the AMP-activated protein kinase pathway (AMPK) in numerous of cell types which promotes the maintenance of different cell structures. This involves autophagic processes and, in particular, may support the renewal of mitochondria. Mitochondrial fitness may protect against oxidative and inflammatory stress - a well-documented effect of oxytocin. The combined specific trophic and protective effects oxytocin may delay several degenerative phenomena including sarcopenia, type-2 diabetes and atherosclerosis. These effects may be exerted both on a central level supporting the function and integrity of the hypothalamus and peripherally acting directly on blood vessels, pancreas, heart, skeletal muscles and adipose tissue etc. Furthermore, in the capacity of being both a hormone and neuromodulator, oxytocin interacts with numerous of regulatory mechanisms particularly the autonomic nervous system and HPA-axis which may reduce blood pressure and affect the immune function. The potential of the oxytocin system as a behavioral and molecular target for the prevention and treatment of cardiovascular disease is discussed. Focus is put on the affiliative and sexual significance and the different options and limitations associated with a pharmaceutical approach. MeSH: Aging, Atherosclerosis, Heart, Hypothalamus, Inflammation, Love, Orgasm, Oxytocin.

Oxytocin, A Possible Treatment for Covid-19? Everything to Gain, Nothing to Lose.

After comparing the morbidity patterns of COVID-19 infections, variations of oxytocin levels and some properties of the neurohormone oxytocin, the authors put forward their hypothesis that oxytocin might constitute a safe, inexpensive and readily available treatment for this disease.

The N363S polymorphism of the glucocorticoid receptor and metabolic syndrome factors in men.

OBJECTIVE: To test the associations between the N363S polymorphism of the glucocorticoid receptor gene (NR3C1) and factors related to the metabolic syndrome in middle-aged men with and without juvenile-onset obesity. RESEARCH METHODS AND PROCEDURES: This study included two groups of middle-aged men, who were originally identified at 20 years of age at the draft boards. One group (n = 208; age, 48 +/- 6 years) was selected on the basis of juvenile-onset obesity (BMI > or = 31 kg/m(2)). The other group consisted of mainly nonobese men randomly sampled from the same population in parallel with the obese men (n = 299; age, 50 +/- 7 years). The subjects were genotyped for the N363S polymorphism by polymerase chain reaction-restriction fragment length polymorphism. Body composition was measured by DXA. Glucose metabolism was evaluated by an oral glucose tolerance test, and the Matsudas index was calculated as a proxy for insulin sensitivity. Serum triglycerides and total and high-density lipoprotein-cholesterol were measured in the fasting state. RESULTS: Among the men with juvenile-onset obesity, carriers (n = 17) of the 363S allele had a lower whole body fat percentage, after accounting for differences in BMI and higher Matsudas index, compared with the noncarriers. The difference in Matsudas index lost statistical significance after the difference in body fat was accounted for. In the randomly sampled men, these variables did not relate to genotype. No relationship between carriers and noncarriers was found in body fat distribution or serum lipids. DISCUSSION: This study suggests that, in men developing obesity early in life, the 363S allele is associated with less adiposity at a given BMI, leading to higher insulin sensitivity.

Low-fat diets and energy balance: how does the evidence stand in 2002?

The role of high-fat diets in weight gain and obesity is assessed by evidence-based principles. Four meta-analyses of weight change occurring on ad libitum low-fat diets in intervention trials consistently demonstrate a highly significant weight loss of 3-4 kg in normal-weight and overweight subjects (P < 0.001). The analyses also find a dose-response relationship, i.e. the reduction in percentage energy as fat is positively associated with weight loss. Weight loss is also positively related to initial weight; a 10 % reduction in dietary fat is predicted to produce a 4-5 kg weight loss in an individual with a BMI of 30 kg/m2. The non-fat macronutrient composition of the diet is also important. Whereas the glycaemic index of the carbohydrate may play a role for cardiovascular risk factors, there is so far no evidence that low-glycaemic index foods facilitate weight control. In contrast, intervention studies show that sugar in drinks is more likely to produce weight gain than solid sugar in foods. Although the evidence is weak, alcoholic beverages promote a positive energy balance, and wine may be more obesity-promoting than beer. Protein is more satiating and thermogenic than carbohydrates, and one intervention study has shown that an ad libitum low-fat diet where carbohydrate was replaced by protein produced more weight loss after 6 months (8.1 v. 5.9 kg). The evidence linking particular fatty acids to body fatness is weak. If anything, monounsaturated fat may be more fattening than polyunsaturated and saturated fats, and no ad libitum dietary intervention study has shown that a normal-fat high-monounsaturated fatty acid diet is equivalent or superior to a low-fat diet in the prevention of weight gain and obesity. The evidence strongly supports the low-fat diet as the optimal choice for the prevention of weight gain and obesity, while the use of a normal-fat high-monounsaturated fatty acid diet is unsubstantiated.

Alcohol drinking and cardiac risk.

The present paper provides a comprehensive review of the literature pertaining to the impact of alcohol intake on cardiovascular disease. Both cross-sectional and prospective studies have disclosed a negative association between moderate intake of alcoholic beverages and cardiovascular disease. The relationship appears to be present for both wine, beer and spirits. Effects of alcohol itself and also the role of different cardio-protective substances in alcoholic beverages are discussed. Alcohol has been suggested to beneficially affect the blood lipid profile, as it increases plasma HDL-cholesterol level. Furthermore, it may inhibit thrombogenesis by reducing thromboxan formation and decreasing the plasma level of fibrinogen. However, high blood concentrations of alcohol may impair fibrinolysis by increasing plasma plasminogen activator inhibitor-1 level. This action could contribute to explaining the 'U'-shaped association between alcohol intake and cardiac events. Alcohol seems to promote abdominal fat distribution, but the importance of this effect in non-obese individuals is uncertain. Wine in particular, but also beer, contains polyphenols which act as antioxidants. Their action could maintain the integrity of the endothelial function by reducing the formation of superoxide. Moreover, these antioxidants may protect against LDL oxidation and modulate the macrophage attack on the endothelium. Although the cardio-protective effect of alcohol can hardly be addressed in healthy individuals by intervention studies with hard end points, there are many observational and experimental findings indicating that moderate alcohol drinking possesses properties preventive of cardiovascular disease.