Moxonidine is a centrally acting, anti-hypertensive medication that exerts additional metabolic properties. It is unknown whether its effects are mediated by neurotransmitters or sympathetic tone regulators, including Neuropeptide Y (NPY). In this study, we evaluated the effects of moxonidine administration on serum NPY in humans. Methods: Ninety individuals with mild or moderate arterial hypertension that required monotherapy were categorized in three age and gender-matched groups according to their Body Mass Index (BMI) as normal weight (n = 30), overweight (n = 30), and obese (n = 30). Moxonidine was administered in therapeutic doses of up to 0.6 mg daily for 12 weeks, and clinical, biochemical and hormonal parameters were recorded. Results: In all three groups, a decrease in systolic and diastolic blood pressure and heart rate was shown. After treatment, BMI, 24 h urine catecholamines and catecholamines’ metabolites, and serum total cholesterol were also reduced. Most importantly, we found a decrease in serum NPY levels in all study groups, with the largest mean decrease in the group of obese and overweight participants compared to normal weight. Conclusions: Moxonidine administration results in improvement in cardio-metabolic parameters, as well as a decrease in serum NPY levels, which therefore represents it being a potent agent against obesity-associated hypertension. Its involvement in energy balance regulation warrants further investigation.
Depression is one of the most common mental illnesses. Impaired neurogenesis is observed in depression. Studying the concentration of biochemical indicators in the blood that may be involved in the pathogenesis of depression, looking for associations with the severity of depressive symptoms can be useful as an objective diagnosis of the disease and predicting the severity of the pathology. We determined plasma concentrations of the monoamine neurotransmitters serotonin and dopamine, and neurotrophic factors involved in neurogenesis (BDNF, CDNF and neuropeptide Y) in depressed patients and healthy volunteers with the same socio-demographic parameters using enzyme immunoassay and mass spectrometry. All study participants were administered the Hamilton Depression Scale (HAMD), the Generalized Anxiety Disorder Questionnaire (GAD-7), and the Center for Epidemiological Studies (CES-D). The cumulative scores on the three scales examined were significantly higher in depressed patients than in controls. The concentration of serotonin, dopamine, BDNF, CDNF, and neuropeptide Y in plasma did not differ between the subject groups and was not associated with the scores on the scales. Positive correlations were found between the content of neuropeptide Y and serotonin, BDNF and CDNF in blood plasma. Thus, although these markers are related to the pathophysiology of depression, they do not correlate with the severity of symptomatology and possibly in plasma cannot reflect processes occurring in the brain.
The present experiments reveal the alterations of the hippocampal neuronal populations in chronic epilepsy. The mice were injected with a single dose of pilocarpine. They had status epilepticus and spontaneously recurrent motor seizures. Three months after pilocarpine treatment, the animals were investigated with the Barnes maze to determine their learning and memory capabilities. Their hippocampi were analyzed 2 weeks later (at 3.5 months) with standard immunohistochemical methods and cell counting. Every animal displayed hippocampal sclerosis. The neuronal loss was evaluated with neuronal-N immunostaining, and the activation of the microglia was measured with Iba1 immunohistochemistry. The neuropeptide Y, parvalbumin, and calretinin immunoreactive structures were qualitatively and quantitatively analyzed in the hippocampal formation. The results were compared statistically to the results of the control mice. We detected neuronal loss and strongly activated microglia populations. Neuropeptide Y was significantly upregulated in the sprouting axons. The number of parvalbumin- and calretinin-containing interneurons decreased significantly in the Ammon’s horn and dentate gyrus. The epileptic animals displayed significantly worse learning and memory functions. We concluded that degeneration of the principal neurons, a numerical decrease of PV-containing GABAergic neurons, and strong peptidergic axonal sprouting were responsible for the loss of the hippocampal learning and memory functions.
Numerous regulatory peptides play a critical role in the pathogenesis of airway inflammation, airflow obstruction and hyperresponsiveness, which are hallmarks of asthma. Some of them exacerbate asthma symptoms, such as neuropeptide Y and tachykinins, while others have ameliorating properties, such as nociception, neurotensin or β-defensin 2. Interacting with peptide receptors located in the lungs or on immune cells opens up new therapeutic possibilities for the treatment of asthma, especially when it is resistant to available therapies. This article provides a concise review of the most important and current findings regarding the involvement of regulatory peptides in asthma pathology.
The phenotype of asthma with obesity is particularly difficult to treat, while its prevalence is increasing. In recent years, special attention has been paid to neuropeptide Y (NPY) due to its possible effect on the severity of the clinical course of asthma.Aim. To identify the relationship between the level of NPY and the clinical course of asthma in patients with obesity and overweight.Methods. The study included 113 patients (27, or 23.89% of men and 86, or 76.11% of women) diagnosed with asthma of moderate severity, whose average age was 57.81 ± 13.05 years. Patients were divided into three groups — with normal body weight, overweight, and obesity. The examination included spirometry, body mass index (BMI), and a questionnaire. Also, Asthma Control Test (ACT) was used. The levels of leptin, adiponectin, NPY, and general oxidative damage were measured in all patients.Results. Asthma control was significantly lower in the group of patients with asthma and obesity compared with the normal body weight and overweight patients. Leptin level was significantly higher in the group of patients with asthma and obesity compared with the normal body weight and overweight patients. The level of NPY was significantly higher in the group of patients with obesity than in the patients with normal body weight and overweight. No significant differences in the level of adiponectin were found between the groups. The NPY level had a high inverse correlation with VLC index, a moderate/medium inverse correlation with forced expiratory volume in 1 sec, forced expiratory flow (FEF) at 25%; forced vital capacity, Tiffno index, FEF 50%, peak expiratory flow, ACT score, and a moderate positive correlation with the level of total oxidative damage.Conclusion. A higher level of NPY is observed in patients with asthma and obesity. This level has an inverse correlation with spirometric parameters, asthma control (evaluated via ACT) and a positive correlation with the level of general oxidative damage, which indicates a possible proinflammatory effect of NPY that contributes to an unfavorable course of asthma. Thus, further studies are required to establish the nature of the relationship between NPY and asthma exacerbations, as well as the mechanism of NPY influence on asthma pathogenesis.
Post-traumatic stress disorder (PTSD) is initiated by traumatic-stress exposure and manifests into a collection of symptoms including increased anxiety, sleep disturbances, enhanced response to triggers, and increased sympathetic nervous system arousal. PTSD is highly co-occurring with alcohol use disorder. Only some individuals experiencing traumatic stress develop PTSD and a subset of individuals with PTSD develop co-occurring alcohol use disorder. To investigate the basis of these individual responses to traumatic stress, single prolonged stress (SPS) a rodent model of traumatic stress was applied to young adult female rats. Individual responses to SPS were characterized by measuring anxiety-like behaviors with open field and elevated plus maze tests. Rats were then allowed to drink ethanol under an intermittent two bottle choice procedure for 8 weeks, and ethanol consumption was measured. An artificial intelligence algorithm was built to predict resilient and vulnerable individuals based on data from anxiety testing and ethanol consumption. This model was implemented in a second cohort of rats that underwent SPS without ethanol drinking to identify resilient and vulnerable individuals for further study. Analysis of neuropeptide Y (NPY) levels and expression of its receptors Y1R and Y2R mRNA in the central nucleus of the amygdala (CeA), basolateral amygdala (BLA), and bed nucleus stria terminalis (BNST) were performed. Results demonstrate that resilient rats had higher expression of Y2R mRNA in the CeA compared with vulnerable and control rats and had higher levels of NPY protein in the BNST compared to controls. The results of the study show that an artificial intelligence algorithm can identify individual differences in response to traumatic stress which can be used to predict subsequent ethanol drinking, and the NPY pathway is differentially altered following traumatic stress exposure in resilient and vulnerable populations. Understanding neurochemical alterations following traumatic-stress exposure is critical in developing prevention strategies for the vulnerable phenotype and will help further development of novel therapeutic approaches for individuals suffering from PTSD and at risk for alcohol use disorder.