Microglia, the resident macrophage-like population in the central nervous system, play a crucial role in the pathogenesis of many neurodegenerative disorders by triggering an inflammatory response ...that leads to neuronal death. Neuroprotective compounds to treat or prevent neurodegenerative diseases are a new field of study in modern medicine. Microglia are activated in response to inflammatory stimuli. The pathogenesis of various neurodegenerative diseases is closely related to the constant activation of microglia due to their fundamental role as a mediator of inflammation in the brain environment. α-Tocopherol, also known as vitamin E, is reported to possess potent neuroprotective effects. The goal of this study was to investigate the biological effects of vitamin E on BV2 microglial cells, as a possible neuroprotective and anti-inflammatory agent, following stimulation with lipopolysaccharide (LPS). The results showed that the pre-incubation of microglia with α-tocopherol can guarantee neuroprotective effects during microglial activation induced by LPS. α-Tocopherol preserved the branched morphology typical of microglia in a physiological state. It also reduced the migratory capacity; the production of pro-inflammatory and anti-inflammatory cytokines such as TNF-α and IL-10; and the activation of receptors such as TRL4 and CD40, which modulate the PI3K-Akt signaling pathway. The results of this study require further insights and research, but they present new scenarios for the application of vitamin E as an antioxidant for the purpose of greater neuroprotection in vivo for the prevention of possible neurodegenerative diseases.
Hypocretin/orexin (ORX) are two hypothalamic neuropeptides discovered in 1998. Since their discovery, they have been one of the most studied neuropeptide systems because of their projecting fields ...innervating various brain areas. The orexinergic system is tied to sleep-wakefulness cycle, and narcolepsy is a consequence of their system hypofunction. Orexinergic system is also involved in many other autonomic functions such as feeding, thermoregulation, cardiovascular and neuroendocrine regulation. The main aim of this mini review article is to investigate the relationship between ORX and thyroid system regulation. Although knowledge about the ORX system is evolving, its putative effects on hypothalamic-pituitary-thyroid (HPT) axis still appear unclear. We analyzed some studies about ORX control of HPT axis to know better the relationship between them. The studies that were analyzed suggest Hypocretin/ORX to modulate the thyroid regulation, but the nature (excitatory or inhibitory) of this possible interaction remains actually unclear and needs to be confirmed.
Orexin-A is a neuropeptide product of the lateral hypothalamus that acts on two receptors, OX1R and OX2R. The orexinergic system is involved in feeding, sleep, and pressure regulation. Recently, ...orexin-A levels have been found to be negatively correlated with renal function. Here, we analyzed orexin-A levels as well as the incidence of SNPs in the hypocretin neuropeptide precursor (HCRT) and its receptors, HCRTR1 and HCRTR2, in 64 patients affected by autosomal dominant polycystic kidney disease (ADPKD) bearing truncating mutations in the PKD1 or PKD2 genes. Twenty-four healthy volunteers constituted the control group. Serum orexin-A was assessed by ELISA, while the SNPs were investigated through Sanger sequencing. Correlations with the main clinical features of PKD patients were assessed. PKD patients showed impaired renal function (mean eGFR 67.8 ± 34.53) and a statistically higher systolic blood pressure compared with the control group (p < 0.001). Additionally, orexin-A levels in PKD patients were statistically higher than those in healthy controls (477.07 ± 69.42 pg/mL vs. 321.49 ± 78.01 pg/mL; p < 0.001). Furthermore, orexin-A inversely correlated with blood pressure (p = 0.0085), while a direct correlation with eGFR in PKD patients was found. None of the analyzed SNPs showed any association with orexin-A levels in PKD. In conclusion, our data highlights the emerging role of orexin-A in renal physiology and its potential relevance to PKD. Further research is essential to elucidate the intricate mechanisms underlying orexin-A signaling in renal function and its therapeutic implications for PKD and associated cardiovascular complications.
Obesity is a multifactorial disease strongly associated with insulin resistance and/or type 2 diabetes mellitus. Correct nutrition represents a valid strategy to fight these dysmetabolic pathologies ...responsible for numerous diseases, including inflammatory and cardiovascular ones. Medical nutrition therapy, including a Mediterranean diet (MD) and a very low-calorie ketogenic diet (VLKCD), is the first-line treatment for prediabetes/diabetes and overweight/obesity. Eighty patients (forty women and forty men) affected by overweight/obesity and type 2 diabetes mellitus or impaired glucose tolerance or impaired fasting glucose (51 (ys) ± 1.75; BMI (kg/m2) 33.08 ± 1.93; HA1c (%): 6.8% ± 0.25) were enrolled at the University Service of Diet Therapy, Diabetology and Metabolic Diseases, Policlinico Riuniti Hospital of Foggia, and subjected to a very-low-calorie Mediterranean diet and a very-low-calorie ketogenic Mediterranean diet for thirty days. Both diets result in a marked decrease in body weight (kg) and BMI (kg/m2). At the same time, only the very-low-calories ketogenic Mediterranean diet reduced waist and hip circumferences. Both diets helped reduce fat mass, but a major loss was achieved in a very low-calorie ketogenic Mediterranean diet. Among gluco-metabolic parameters, only the very-low-calorie ketogenic Mediterranean diet group showed a significant decrease in fasting blood glucose and HbA1c, insulin, C-peptide total cholesterol, LDL, and triglycerides. The results of our study seem to show that the very-low-calorie ketogenic Mediterranean diet is a good strategy to improve rapidly metabolic, anthropometric, and body composition parameters in patients with prediabetes or diabetes and overweight/obesity.
Autism spectrum disorders (ASD) is a complex and multifaceted neurobehavioral syndrome with no specific cause still identified, despite the worldwide increasing (prevalence for 1,000 children from ...6.7 to 14.6, between 2000 and 2012). Many biological and instrumental markers have been suggested as potential predictive factors for the precocious diagnosis during infancy and/or pediatric age. Many studies reported structural and functional abnormalities in the autonomic system in subjects with ASD. Sleep problems in ASD are a prominent feature, having an impact on the social interaction of the patient. Considering the role of orexins (A and B) in wake-sleep circadian rhythm, we could speculate that ASD subjects may present a dysregulation in orexinergic neurotransmission. Conversely, oxidative stress is implicated in the pathophysiology of many neurological disorders. Nonetheless, little is known about the linkage between oxidative stress and the occurrence or the progress of autism and autonomic functioning; some markers, such as heart rate (HR), heart rate variability (HRV), body temperature, and galvanic skin response (GSR), may be altered in the patient with this so complex disorder. In the present paper, we analyzed an autism case report, focusing on the rule of the sympathetic activity with the aim to suggest that it may be considered an important tool in ASD evaluation. The results of this case confirm our hypothesis even if further studies needed.
Summary
Heart rate variability (HRV) is altered in obese subjects, but whether this is true also in underweight (UW) subjects is still under debate. We investigated the HRV profile in a sample of ...healthy adult women and its association with adiposity. Five‐minute resting state electrocardiographic activity was recorded in 69 subjects grouped according to their body mass index, 23 normal weight (NW), 23 overweight/obese (OW) and 23 UW). Body fat mass (FM) was measured by bio‐impedance. Frequency‐ and time‐domain analyses were performed. Compared to NW, UW and OW subjects showed a significant decrease in HRV indices, as revealed by spectral analysis. No differences were observed between UW and OW subjects. A second‐order polynomial regression unveiled an inverted U‐shaped relationship between FM extent and HRV indices. A decrease of HRV indices was associated with changes in FM extent, proving that in UW and OW subjects, the adaptive flexibility of autonomic cardiac function was reduced. These findings provide important clues to guide future studies addressed to determine how changes in adiposity and autonomic cardiac function may contribute to health risk.
Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease, responsible for a global pandemic that began in January 2020. Human/COVID-19 interactions cause different outcomes ...ranging from minor health consequences to death. Since social interaction is the default mode by which individuals communicate with their surroundings, different modes of contagion can play a role in determining the long-term consequences for mental health and emotional well-being. We examined some basic aspects of human social interaction, emphasizing some particular features of the emotional contagion. Moreover, we analyzed the main report that described brain damage related to the COVID-19 infection. Indeed, the goal of this review is to suggest a possible explanation for the relationships among emotionally impaired people, brain damage, and COVID-19 infection.
COVID-19 can cause several significant neurological disorders and the pandemic has been linked to a rise in people reporting mental health problems, such as depression and anxiety. Neurocognitive symptoms associated with COVID-19 include delirium, both acute and chronic attention and memory impairment related to hippocampal and cortical damage, as well as learning deficits in both adults and children.
Although our knowledge on the biology and long-term clinical outcomes of the COVID-19 infection is largely limited, approaching the pandemic based on lessons learnt from previous outbreaks of infectious diseases and the biology of other coronaviruses will provide a suitable pathway for developing public mental health strategies, which could be positively translated into therapeutic approaches, attempting to improve stress coping responses, thus contributing to alleviate the burden driven by the pandemic.
Exercise represents the most important integrative therapy in metabolic, immunologic and chronic diseases; it represents a valid strategy in the non-pharmacological intervention of lifestyle linked ...diseases. A large body of evidence indicates physical exercise as an effective measure against chronic non-communicable diseases. The worldwide general evidence for health benefits are both for all ages and skill levels. In a dysregulated lifestyle such as in the obesity, there is an imbalance in the production of different cytokines. In particular, we focused on Adiponectin, an adipokine producted by adipose tissue, and on Orexin-A, a neuropeptide synthesized in the lateral hypothalamus. The production of both Adiponectin and Orexin-A increases following regular and structured physical activity and both these hormones have similar actions. Indeed, they improve energy and glucose metabolism, and also modulate energy expenditure and thermogenesis. In addition, a relevant biological role of Adiponectin and Orexin A has been recently highlighted in the immune system, where they function as immune-suppressor factors. The strong connection between these two cytokines and healthy status is mediated by physical activity and candidates these hormones as potential biomarkers of the beneficial effects induced by physical activity. For these reasons, this review aims to underly the interconnections among Adiponectin, Orexin-A, physical activity and healthy status. Furthermore, it is analyzed the involvement of Adiponectin and Orexin-A in physical activity as physiological factors improving healthy status through physical exercise.
Depression of electrocorticogram propagating over the cortex surface results in cortical spreading depression (CSD), which is probably related to the pathophysiology of stroke, epilepsy, and ...migraine. However, preconditioning with CSD produces neuroprotection to subsequent ischemic episodes. Such effects require the expression or activation of several genes, including neuroprotective ones. Recently, it has been demonstrated that the expression of the uncoupling proteins (UCPs) 2 and 5 is amplified during brain ischemia and their expression exerts a long-term effect upon neuron protection. To evaluate the neuroprotective consequence of CSD, the expression of UCP-5 in the brain cortex was measured following CSD induction. CSD was evoked in four samples of rats, which were sacrificed after 2 hours, 4 hours, 6 hours, and 24 hours. Western blot analyses were carried out to measure UCP-5 concentrations in the prefrontal cortices of both hemispheres, and immunohistochemistry was performed to determine the localization of UCP-5 in the brain cortex. The results showed a significant elevation in UCP-5 expression at 24 hours in all cortical strata. Moreover, UCP-5 was triggered by CSD, indicating that UCP-5 production can have a neuroprotective effect.
Sleep and migraine share a common pathophysiological substrate, although the underlying mechanisms are unknown. The serotonergic and orexinergic systems are both involved in the regulation of ...sleep/wake cycle, and numerous studies show that both are involved in the migraine etiopathogenesis. These two systems are anatomically and functionally interconnected. Our hypothesis is that in migraine a dysfunction of orexinergic projections on the median raphe (MR) nuclei, interfering with serotonergic regulation, may cause Non-Rapid Eye Movement parasomnias, such as somnambulism.
Acting on the serotonergic neurons of the raphe nuclei, the dysfunction of orexinergic neurons would lead to a higher release of serotonin. The activation of serotonergic receptors located on the walls of large cerebral vessels would lead to abnormal vasodilatation and consequently increase transmural pressure. This process could activate the trigeminal nerve terminals that innervate vascular walls. As a consequence, there is activation of sensory nerve endings at the level of hard vessels in the meninges, with release of pro-inflammatory peptides (e.g., substance P and CGRP). Within this hypothetical frame, the released serotonin could also interact with trigeminovascular afferents to activate and/or facilitate the release of the neuropeptide at the level of the trigeminal ganglion. The dysregulation of the physiological negative feedback of serotonin on the orexinergic neurons, in turn, would contribute to an alteration of the whole system, altering the sleep-wake cycle.
Serotonergic neurons of the MR nuclei receive an excitatory input from hypothalamic orexin/hypocretin neurons and reciprocally inhibit orexin/hypocretin neurons through the serotonin 1A receptor (or 5-HT1A receptor). Considering this complex system, if there is an alteration it may facilitate the pathophysiological mechanisms involved in the migraine, while it may produce at the same time an alteration of the sleep-wake rhythm, causing sleep disorders such as sleepwalking. Understanding the complex mechanisms underlying migraine and sleep disorders and how these mechanisms can interact with each other, it would be crucial to pave the way for new therapeutic strategies.
PDF
