Protective effects of chronic humanin treatment in mice with diabetic encephalopathy: A focus on oxidative stress, inflammation, and apoptosis.

Diabetes is known to cause cognitive impairments through various mechanisms, including oxidative stress, inflammation, and apoptosis. Humanin (HN) has been shown to have protective effects on cognitive impairments induced by factors such as Aß, muscarinic receptor antagonists, and aging in rodents. However, the mechanisms underlying the protective effects of HN in the prefrontal cortex and hippocampus in the context of diabetes are not well understood. In this study, we aimed to investigate the potential protective role of HN on oxidative stress, inflammation, and apoptosis in mice with diabetes. We divided the mice into four groups, including a control group (treated with saline), a humanin group (treated with 4 mg/kg of HN), a streptozotocin (STZ) group (diabetic control), and an STZ+Humanin group. The mice were administered HN daily for 15 days. Our results showed that in the prefrontal cortex and hippocampus of the diabetes group, oxidative stress parameters, pro-inflammatory cytokines, apoptosis and, blood glucose levels were increased, while antioxidant and anti-inflammatory cytokines were diminished compared to the control group. However, HN treatment was able to modulate these markers, including blood glucose and the markers of oxidative stress, inflammation, and apoptosis. In conclusion, our findings suggest that hyperglycemia, oxidative stress, inflammation, and apoptosis may contribute to the development of diabetes-induced cognitive impairments. By regulating these changes with HN treatment, we may be able to positively contribute to the treatment of cognitive impairments induced by diabetes.

The Effects of Chronic Asprosin Administration on Sense of Smell and Sexual Behavior in Female Rats.

INTRODUCTION: Asprosin is an adipokine released from white adipose tissue during fasting and acts through the olfactory receptor. It is known that adipokines play roles in reproductive physiology in mammals. However, there are very few studies conducted on role of asprosin in reproductive functions. There are no studies on its relationship with sexual motivation. It was shown in the literature that administration of asprosin to male mice improves olfaction. It is also known that there is a strong correlation between smell and sexual desire. In view of this, it was hypothesized that chronic administration of asprosin would improve olfactory performance and increase sexual incentive motivation in female rats for male partners. METHODS: This hypothesis was tested by applying the hidden cookie test, sexual incentive test, active research test, and sexual behavior test. The changes in serum hormone levels in female rats that chronically received asprosin were also measured and compared. RESULTS: Chronic asprosin exposure increased olfactory performance, male preference ratio, male investigation preference ratio, activity index, and anogenital investigation behavior. Also, serum oxytocin and estradiol levels increased following chronic administration of asprosin in female rats. CONCLUSION: These data suggest that chronic administration of asprosin can result in increased sexual incentive motivation for opposite sex in female rats over increased olfactory performance and changes in reproductive hormones.

Effects of chronic irisin treatment on brain monoamine levels in the hypothalamic and subcortical nuclei of adult male and female rats: An HPLC-ECD study.

Monoaminergic systems are known to be involved in the pathophysiology of neuropsychiatric disorders and vegetative functions due to their established influence on hypothalamic and subcortical areas. These systems can be modulated by lifestyle factors, especially exercise, which is known to produce several beneficial effects on reproduction, brain health, and mental disorders. The fact that exercise is sensed by the brain shows that muscle-stimulated secretion of myokines allows direct crosstalk between the muscles and the brain. One of such exercise-induced beneficial effects on the brain is exhibited by irisin-a recently discovered PGC-1α-dependent adipo-myokine mainly secreted from skeletal muscle during exercise. Thus, we hypothesized that irisin may affect central monoamine levels and thus play an important role in the muscle-brain endocrine loop. To test this assertion, for 10 weeks, vehicle (deionized water) or 100 ng/kg irisin was injected intraperitoneally once a day to 12 male and 12 female rats after which the levels of monoamines and their metabolites were determined by HPLC-ECD. In the hypothalamic nuclei, irisin significantly decreased dopamine (DA) metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) (p < 0.05), DOPAC/DA ratio (p < 0.01) and noradrenaline (NA, p < 0.05) levels in the anteroventral periventricular nucleus (AVPV), and DOPAC and NA levels in the medial preoptic area (mPOA) (p < 0.05), having a crucial role in reproduction and sexual motivation, respectively. On the other hand, irisin significantly increased DOPAC levels in the lateral hypothalamic area (LHA) (p < 0.05), which acts as a hunger center, while it significantly decreased the levels of DA, NA, and its metabolite 3,4-dihydroxyphenylglycol (DHPG) in the ventromedial hypothalamic nucleus (VMH) as a known satiety center (p < 0.05). In nucleus accumbens (NaC), irisin significantly reduced 5-hydroxyindoleacetic acid (5-HIAA) levels (p < 0.05), which are implicated in autism spectrum disorder (ASD) physiopathology. It also significantly increased DA levels in this area, thus exhibiting positive effects on depression and sexual dysfunction in men. On the other hand, it significantly decreased serotonin (5-HT) (p < 0.01) and its metabolite 5-HIAA levels in the medial amygdala (MeA) (p < 0.05), indicating that it may play a role in social behaviors. Moreover, it significantly attenuated NA levels in the same subcortical area (p < 0.01), which is directly involved in stress-induced activation of the central noradrenergic system. These findings demonstrate for the first time that irisin induces significant changes in monoamine levels in many hypothalamic nuclei involved in feeding behavior and vegetative functions, as well as in subcortical nuclei related to neuropsychiatric disorders.