Neurotransmitter Norepinephrine Research Articles

Phenotypic and functional disparities in perivascular adipose tissue

The adipose tissue surrounding blood vessels is known as perivascular adipose tissue (PVAT), which represents a distinct ectopic fat depot that adheres to the majority of the vasculature. In recent years, owing to its unique location and function, PVAT has been regarded as a new type of adipose tissue distinct from traditional visceral fat. It releases adipokines with vasoconstrictive functions, which regulate vascular function through paracrine and endocrine mechanisms. Interestingly, PVAT can be categorized as white, brown or a mixture of both depending on its anatomical location. Brown adipose tissue (BAT) is located adjacent to the thoracic aorta in rodents, while a mix of brown and white tissue surrounds the abdominal aorta. PVAT exhibits regional phenotypic differences in different parts of the vasculature bed, which may lead to heterogeneity in the secretion profiles and norepinephrine (NE) content in regional PVAT and subsequently affect the regulation of specific adipokine signaling pathways in regional PVAT, resulting in differences in the regulation of vascular function. The aim of this review was to explore the potential factors that influence the anticontractile function of regional PVAT in the vasculature, including the heterogeneity of regional PVAT, the anticontractile function mediated by endothelial nitric oxide synthase (eNOS) in regional PVAT, the activity of the adiponectin-eNOS pathway in regional PVAT adipocytes, and the concentration of the sympathetic neurotransmitter NE in regional PVAT.

The Sexual Dimorphism of the Neuroimmune Response in the Brains of Taenia crassiceps-Infected Mice

Background: Helminth infections are associated with cognitive deficits, especially in school-age children. Deworming treatment in heavily infected children improves their short- and long-term memory recall. In mice, intraperitoneal helminth infection with Taenia crassiceps (T. crassiceps) shows sexual dimorphism in terms of the parasite load, immune response, hormone levels, and behavioral changes. We have previously shown poorer short-term memory performance and changes in the concentrations of cytokines and neurotransmitters in the hippocampus, which were replicated in this study. The molecular changes in other brain structures, such as those related to reproduction, are unknown. Methods: Male and female Balb/cAnN mice were chronically infected with T. crassiceps larvae. We determined the peritoneal parasite load and established the presence of cytokines and neurotransmitters in the hippocampus, olfactory bulb, and hypothalamus. Results: The parasite load was higher in female than male infected mice, as expected. In the hippocampus, the neurotransmitters norepinephrine and serotonin increased in males but decreased in females. In contrast, in the olfactory bulb and hypothalamus, the neurotransmitters assessed showed no statistical differences. The cytokine profiles were different in each brain structure. The TNF-α levels in the olfactory bulb and the IL-4 levels in the hippocampus of infected mice were dimorphic; IFN-γ was augmented in both male and female infected animals, although the increase was higher in infected males. Conclusions: The brain responds to peripheral infection with cytokine levels that vary from structure to structure. This could be a partial explanation for the dimorphic behavioral alterations associated with infection, it also demonstrates the synergic interaction between the immune, the endocrine, and the nervous systems.

Mouse liver blood flow is regulated by hepatic stellate cells in response to the sympathetic neurotransmitter norepinephrine

BackgroundThere is no clear information on the regulation of liver blood flow by the autonomic nervous system. We conducted this study to investigate whether quiescent hepatic stellate cells (qHSCs) regulate liver blood flow in response to the sympathetic neurotransmitter norepinephrine (NE). MethodsqHSCs isolated from mice were cultured in Dulbecco's modified Eagle medium without fetal bovine serum for 1 day on collagen gel. NE-induced qHSC contraction was evaluated using the quantitative single-cell contraction measurement method that we had developed previously. For the measurement of liver perfusion pressure in situ, a buffer solution was perfused from the portal vein in mice. ResultsNE-induced a reversible contraction of qHSCs. This contraction was suppressed by the nonmuscle myosin II inhibitor blebbistatin, the myosin light chain kinase inhibitor ML-9, the Rho kinase inhibitor H-1152, the calmodulin inhibitor W-7, the store-operated calcium channel inhibitor YM-58483, and the IP3 receptor inhibitor xestospongin C. In contrast, the transient receptor potential C channel inhibitor SKF96365 did not affect the NE-induced contraction. ConclusionThese results suggest that qHSCs contract in response to NE. New & noteworthyThe present study provides direct evidence for the first time that norepinephrine (NE) induces a reversible contraction of isolated single quiescent hepatic stellate cells (qHSCs) and further suggests that the NE-mediated qHSC contraction participates in the regulation of liver blood flow in vivo.

Optimizing the anesthetic care of patients with aromatic l-amino acid decarboxylase deficiency.

Aromatic l-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive disorder that results in a lack of the monoamine neurotransmitters dopamine, serotonin, norepinephrine, and epinephrine. Patients present with a wide spectrum of symptoms, including motor and autonomic dysfunction, hypotonia, and developmental delay, often before the age of one. Until recently, treatment options were limited to symptom control, but the recent approval of the first gene therapy for AADC deficiency in Europe and the UK has provided an alternative to treating symptoms for this disease. Eladocagene exuparvovec is a one-time gene therapy, administered bilaterally to the putamen by magnetic resonance imaging-guided stereotactic neurosurgery. While administration of the gene therapy itself is minimally invasive, the anesthetic management of patients with AADC deficiency is challenging due to the absence of sympathetic regulation secondary to the lack of adrenergic neurotransmitters. Optimal anesthetic management requires an understanding of the complex and heterogeneous nature of the disease. Hemodynamic instability, temperature dysregulation, and hypoglycemia are of primary concern, but there are also challenges regarding intravenous access and airway management. A thorough preoperative assessment is essential and should be guided by the patient's history. Advanced planning is necessary regarding the timing of the procedure schedule and operative plan; meticulous preparation, simulation for the operating room, as well as communication with all perioperative staff members, are crucial. Intraoperatively, utmost care must be taken to protect the skin, maintain body temperature, and to prepare for inotropic and/or glycemic support as needed. Postoperative intensive care management is necessary for consideration of postoperative extubation and provision of supportive care. With careful planning, preparation, and vigilance, patients with AADC deficiency can safely undergo anesthesia.

Yeast Extract Peptides Alleviate Depression in Chronic Restraint Stress Rats by Alleviating Hippocampal Neuronal Apoptosis and Dysbiosis of the Gut Microbiota.

Depression as a global neurological disorder, and hippocampal neuronal apoptosis and disorders of the gut microbiota are closely related to it. This study aims to expose the ameliorative effect of enzyme peptides (AP) from brewer's yeast on depressive behavior caused by chronic restraint stress (CRS) in rats. After 4 weeks of AP intervention, a significant alleviation of depressive behavior in the sucrose preference test (SPT), forced swim test (FST), and light-dark test (LDT) is observed in depressed rats. AP ameliorates neuronal damage with increased the expression of the key CREB/BDNF/TrkB/Akt signaling pathway, which increases the levels of the monoamine neurotransmitters 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in the hippocampus, buffering hyperactivity of the hypothalamo-pituitary-adrenal axis (HPA), and decreasing the serum cortisol (CORT) and adrenocorticotropic hormone (ACTH) levels in rats. In addition, AP modulates the disruption of the rat gut microbiota by chronic restraint stress (CRS), and the changes in the abundance of Lactobacillus animalis and Lactobacillus johnsonii are probably the key for AP performing antidepressant benefits. A strong correlation is found between gut microbiota and biochemical markers of depression. AP, as a natural and safe active substance, has a positive effect in the treatment of depression.

RGS Proteins in Sympathetic Nervous System Regulation: Focus on Adrenal RGS4.

The sympathetic nervous system (SNS) consists largely of two different types of components: neurons that release the neurotransmitter norepinephrine (NE, noradrenaline) to modulate homeostasis of the innevrvated effector organ or tissue and adrenal chromaffin cells, which synthesize and secrete the hormone epinephrine (Epi, adrenaline) and some NE into the blood circulation to act at distant organs and tissues that are not directly innervated by the SNS. Like almost every physiological process in the human body, G protein-coupled receptors (GPCRs) tightly modulate both NE release from sympathetic neuronal terminals and catecholamine (CA) secretion from the adrenal medulla. Regulator of G protein Signaling (RGS) proteins, acting as guanosine triphosphatase (GTPase)-activating proteins (GAPs) for the Gα subunits of heterotrimeric guanine nucleotide-binding proteins (G proteins), play a central role in silencing G protein signaling from a plethora of GPCRs. Certain RGS proteins and, in particular, RGS4, have been implicated in regulation of SNS activity and of adrenal chromaffin cell CA secretion. More specifically, recent studies have implicated RGS4 in regulation of NE release from cardiac sympathetic neurons by means of terminating free fatty acid receptor (FFAR)-3 calcium signaling and in regulation of NE and Epi secretion from the adrenal medulla by means of terminating cholinergic calcium signaling in adrenal chromaffin cells. Thus, in this review, we provide an overview of the current literature on the involvement of RGS proteins, with a particular focus on RGS4, in these two processes, i.e., NE release from sympathetic nerve terminals & CA secretion from adrenal chromaffin cells. We also highlight the therapeutic potential of RGS4 pharmacological manipulation for diseases characterized by sympathetic dysfunction or SNS hyperactivity, such as heart failure and hypertension.

PARAPHILIA AND MAJOR DEPRESSIVE DISORDERS: PREVALENCE AND PATHOGENESIS

Introduction - Paraphilia disorders are defined as an abnormal intense sexual deviant followed by behaviors to fulfill fierce sexual erotic activities. Major depressive disorder (MDD) is a mood disorder marked by the appearance of a depressed mood, decreased interest, poor cognitive function, and vegetative symptoms including sleep or eating disorders. There is a study about the prevalence of paraphilia in the US, 15,9%. Meanwhile, there is about 6,1% of the prevalence of depressive disorders in Indonesia. According to DSM-5, Paraphilias, and paraphilia-related disorders, depressive disorders are the most frequent comorbid axis I diagnoses with a lifetime prevalence of life by 56%. Based on these case numbers, this study aims to discuss the correlation between these two events. Methods - Researchers used several journals and textbooks discussing the prevalence and pathogenesis of paraphilia and major depressive disorders; and the correlation between these two disorders. Results - Paraphilias are rarely diagnosed in clinical settings because many cases of paraphilia are related to illegal and criminal acts (such as sexual harassment), and reporting methods are unreliable, meanwhile depression is ubiquitous in both high and low-income countries. This shows that any government needs to be aware of the effects of depressive disorders. Those who have not sought treatment are still high, amounting to 87 to 91% of depressive disorders that have not sought treatment. Discuss - There is a significant correlation between paraphilia and major depressive disorder, MDD is one of the paraphilia-related disorders comorbid axis I diagnosis with a lifespan prevalence of 56%. From the pathogenesis, monoamine neurotransmitters dopamine, norepinephrine, and serotonin serve a modulatory role in human sexual motivation, appetitive, and consummatory behavior. Conclusion - In pathogenesis, there's a degradation in function, amount, and production of neurotransmitter monoamine, dopamine, norepinephrine, and serotonin that cause the person with paraphilia usually show symptoms such as mood changes, decreased interest, depression, decreased cognitive function, and the appearance of vegetative-related symptoms such as impaired appetite or sleep activity. Keywords: paraphilias, depression, pathogenesis.

Analytical Methods for Tetracyclic Antidepressants: A Comprehensive Review

ABSTRACTDepression is a mental illness that affects patients’ behavior, and it impacts approximately 264 million people globally. Tetracyclic antidepressants (TeCAs) are one class of medication that is available for the treatment of depression. These medications work by modifying hormones such as serotonin, norepinephrine, and dopamine. TeCAs, such as setiptiline, amoxapine, mianserin, maprotiline, and mirtazapine, are four ring‐based compounds that assist in preventing the brain from reabsorbing the neurotransmitters norepinephrine and serotonin. Each of these medications interacts with adrenergic (α1 and α2) and serotonin (5HT1 and 5HT2) receptors independently. Using biological samples (plasma, blood, and urine) and pharmaceutical formulations, this review focuses on providing a complete overview of the various analytical conditions maintained for the medications in the above class and their metabolites. Major analytical methods such as mass spectrometry, gas chromatography, and high‐performance liquid chromatography are used to quantify and determine the drugs. This review provides a thorough understanding of impurity identification, pharmacokinetic and stability evaluations, and structural degradation quantification. It provides valuable and reliable information for research, enhancing their understanding of the subject matter.

Behavioral dysregulation in Nile tilapia (Oreochromis niloticus, GIFT) post-Streptococcus agalactia infection: Role of the microbiota-gut-brain axis

In the aquatic farming industry, understanding the factors affecting fish behavior is crucial, particularly in response to infections that compromise welfare and productivity. Swimming performance is a key life history trait critical to their ecology. This study explores the swimming behavior imbalance in Nile tilapia (Oreochromis niloticus, GIFT) post-infection with Streptococcus agalactiae (GBS), a common pathogen responsible for significant losses in aquaculture. We focused on how the microbiota-gut-brain axis influences the behavioral response of tilapia to GBS infection. Behavioral changes were quantified by measuring collision times and swimming speeds, which decreased significantly following infection. This behavioral downturn is mediated by alterations in the microbiota-gut-brain axis, evidenced by increased levels of monoamine neurotransmitters (serotonin, norepinephrine, and dopamine) in the brain and intestinal tissues. The study utilized pharmacological agents, the 5-HT1A receptor agonist (8-OH-DPAT) and antagonist (WAY-100635), to investigate their efficacy in mitigating these behavioral and biochemical changes. Both agents partially restored normal behavior by adjusting neurotransmitter concentrations disrupted by GBS infection. Additionally, a notable increase in the relative abundance of Streptococcus within the gut microbiota of infected fish highlights the potential role of specific bacterial populations in influencing host behavior. This research provides novel insights into the complex interactions between pathogen-induced gut microbiota changes and Nile tilapia's behavioral outcomes, highlighting potential avenues for improving fish health management through microbiota-targeted interventions.

Beta vulgaris Betalains Mitigate Parasitemia and Brain Oxidative Stress Induced by Plasmodium berghei in Mice.

Although many drugs have been discovered to treat malaria infection, many of them face resistance from the host's body with long-term use. Therefore, this study aimed to evaluate the activity of betalains (from Beta vulgaris) and chloroquine (a reference drug) against brain oxidative stress induced by Plasmodium berghei in male mice. Two protocols were applied in this study: the therapeutic and prophylactic protocols. The results of the therapeutic protocol revealed a significant decrease in the level of parasitemia caused by P. berghei. Additionally, the histopathological changes in various brain regions were markedly improved after treatment with betalains. Regarding the prophylactic protocol, betalains were able to protect the brain tissues from oxidative stress, inflammation, and disrupted neurotransmitters expected to occur as a result of infection by P. berghei. This was demonstrated by modulating the activities of brain antioxidants (SOD and GSH), inflammatory cytokines (IL-6, IL-10, IL-12, TNF-α, and INF-γ), and neurotransmitters (serotonin, epinephrine, and norepinephrine). This study has proven that using betalains as a treatment or as a preventive has a vital and effective role in confronting the brain histopathological, oxidative stress, and inflammatory changes induced by P. berghei infection.

Long-term exposure to ionic liquid [C8mim]Br induces the potential risk of anxiety and memory deterioration through disturbing neurotransmitter systems

1-octyl-3-methylimidazolium bromide ([C8mim]Br), one of the ionic liquids (ILs), has been used in various fields as an alternative green solvent of conventional organic solvents. Increased application and stabilization of imidazole ring structure lead to its release into the aquatic environment and long-term retention. Structure-activity relationship consideration suggested that ILs may be acetylcholinesterase inhibitors; however, neurotoxicity in vivo, especially the underlying mechanisms is rarely studied. In this study, the zebrafish were exposed to 2.5–10 mg/L [C8mim]Br for 28 days to comprehensively evaluate the neurotoxicity of ILs on adult zebrafish from the behavioral profiles and neurotransmitter systems for the first time. The results indicate that zebrafish exhibit suppressed spatial working memory and anxious behaviors. To assess the potential neurotoxic mechanisms underlying the behavioral responses of zebrafish, we measured the levels of neurotransmitters and precursors, key enzyme activities, and expression levels of relevant genes. Nissl staining showed significant neural cell death in zebrafish after 28-day [C8mim]Br exposure, with corresponding decreases in the levels of neurotransmitters (acetylcholine, glutamate, 5-hydroxytryptophan, gamma-aminobutyric acid, dopamine, and norepinephrine). Furthermore, these results were associated with mRNA expression levels of the disrupted neurotransmitter key genes (th, tph2, mao, slc6a3, ache, gad67). Overall, our study determined that [C8mim]Br caused potential mental disorders like anxiety and memory deterioration in zebrafish by impairing neurotransmitter systems, providing recommendations for the industrial production and application of [C8mim]Br.

The Impact of Physical Activity on Depression Treatment: A Literature Review

Introduction Engaging in physical exercise can have a significant impact on the treatment of mild-to-moderate mental health conditions, including depression. Existing antidepressant medications have limited clinical effectiveness as they fail to achieve a complete response in around 30% of depressed patients and do not induce remission in these individuals. Physical exercise can enhance the effects of antidepressant therapy in individuals with depression by boosting the health of neurons and improving the responsiveness to medication. Aim of the study The aim of the study is to investigate the role of physical activity in in the management of mental health diseases, especially depression. Materials and methods This study represents the current state of knowledge about the antidepressant effects of physical activity, particularly in the context of depressive disorders. It presents a comprehensive overview of how regular exercise can serve as an effective therapeutic strategy for managing depressive symptoms. PubMed and Google Scholar database was searched for articles written in English. The search included the keywords. Results Regular exercise significantly alleviates depressive symptoms through various mechanisms. Exercise enhances the production of endorphins, which improve mood and reduce anxiety. It also influences neurotransmitter systems, including serotonin, dopamine, and norepinephrine, which are crucial in regulating mood and emotion. Additionally, physical activity stimulates the production of brain-derived neurotrophic factor (BDNF) and transforming growth factor-beta 1 (TGF-β1), both of which support neurogenesis and synaptic plasticity, contributing to improved cognitive function and mood stabilization.

Gastrodin Ameliorates Learning and Memory Impairments Caused by Long-Term Noise Exposure.

The developing brain is significantly affected by long-term exposure to noise at an early age, leading to functional disorders such as learning and memory impairments. Gastrodin (GAS), a natural organic compound, is an extraction of phenolic glycoside from the rhizome of Gastrodia elata. Clinically, GAS is extensively utilised for the treatment of neurological disorders. This study aimed to explore the effect and mechanism of GAS on noise exposure-induced learning and memory impairments. Rats aged 21 days were exposed to a 90 dB noise environment for 4 weeks and divided into the noise group, the noise + GAS group, and the control group to establish a noise exposure model. After noise exposure treatment, the improvement effect of GAS on the memory of rats was evaluated by Y-maze and Morris water maze. Enzyme-linked immunosorbent assay was utilised to determine the effect of GAS on neurotransmitter levels in the hippocampal tissue of noise-exposed rats. Western blot was applied for the detection of the protein levels of neurotrophic factors. The GAS treatment significantly improved spatial memory and increased the levels of key neurotransmitters (norepinephrine, dopamine and serotonin) and neurotrophic factors (neurotrophin-3 and brain-derived neurotrophic factor) in the hippocampal tissues of noise-exposed rats. These alterations correlate with enhanced cognitive functions, suggesting a neuroprotective effect of GAS against noise-induced cognitive impairments. This study supports the potential of GAS to treat noise-induced learning and memory impairments by modulating neurotransmitter secretion and enhancing the expression levels of neurotrophic factors. These findings offer potential therapeutic avenues for cognitive impairments induced by noise exposure.

Genetic factors associated to Alzheimer’s Disease

Alzheimer's disease is a neurological condition that gradually impairs memory, self-awareness, and cognitive capacities. It is the most frequent cause of dementia and a major factor in senior patient deaths. It is generally acknowledged that the condition is multifactorial, resulting from intricate interactions between age, genetics, and environment, even though the exact cause is unknown. Early start of the condition can be caused by mutations in the APP, PSEN1, and PSEN2 genes, which can result in an autosomal dominant inheritance pattern. The most prevalent kind is late-onset, in which the APOE ε4 allele is the primary genetic risk factor. TREM2, CLU, and PICALM are among the other genes that raise the risk. The primary molecular pathways are the build-up of beta-amyloid proteins, which result in amyloid plaques, and the hyperphosphorylation of tau, which forms neurofibrillary tangles and causes neuronal death by necrosis, autophagy, and apoptosis. Acetylcholine, glutamate, GABA, and noradrenaline neurotransmission are all impacted, which has an effect on cognition and memory.In conclusion, Alzheimer's disease is a complicated neurological disorder that causes progressive cognitive impairment due to both hereditary and molecular components.

Effects of acute inhibition of dopamine β-hydroxylase on neural responses to pups in adult virgin male California mice (Peromyscus californicus)

The neural mechanisms underlying paternal care in biparental mammals are not well understood. The California mouse (Peromyscus californicus) is a biparental rodent in which virtually all fathers are attracted to pups, while virgin males vary widely in their behavior toward unrelated infants, ranging from attacking to avoiding to huddling and grooming pups. We previously showed that pharmacologically inhibiting the synthesis of the neurotransmitter norepinephrine (NE) with the dopamine β-hydroxylase inhibitor nepicastat reduced the propensity of virgin male and female California mice to interact with pups. The current study tested the hypothesis that nepicastat would reduce pup-induced c-Fos immunoreactivity, a cellular marker of neural activity, in the medial preoptic area (MPOA), medial amygdala (MeA), basolateral amygdala (BLA), and bed nucleus of the stria terminalis (BNST), brain regions implicated in the control of parental behavior and/or anxiety. Virgin males were injected with nepicastat (75 mg/kg, i.p.) or vehicle 2 hours prior to exposure to either an unrelated pup or novel object for 60 minutes (n = 4–6 mice per group). Immediately following the 60-minute stimulus exposure, mice were euthanized and their brains were collected for c-Fos immunohistochemistry. Nepicastat reduced c-Fos expression in the MeA and MPOA of pup-exposed virgin males compared to vehicle-injected controls. In contrast, nepicastat did not alter c-Fos expression in any of the above brain regions following exposure to a novel object. Overall, these results suggest that the noradrenergic system might influence MeA and MPOA function to promote behavioral interactions with pups in virgin males.

Antidepressant Effect of Vincamine, Melatonin and their Combination in Experimental Rat Models of Depression

Background: Depression, a form of mood illness, is characterized by a lack of or diminished social life, melancholy, and symptoms linked to an uplifted or depressed mood. Vincamine and Melatonin combination may prove beneficial for treating depression because vincamine and melatonin have already been reported in the treatment of dementia. Dementia is a CNS disorder which is connected to the level of neurotransmitters at the synaptic cleft, which is similar to depression that is why it might be effective in the treatment of depression. Aim: The aim of this research is to conduct an experimental study on the antidepressant activity of Vincamine alone and along with Melatonin and comparison with standard antidepressant drugs. Method: In this study, all animals are trained for the experiment, and then animals are divided into groups according to the treatment protocol. Animals were placed for the rest for 1 week. Vincamine and melatonin were administered to the treated groups on days 8 and 21 for the behavioral analysis using different kinds of models like elevated plus maze, forced swim test, open field test and sucrose preference test. Animals were sacrificed at day 22 for the estimation of biochemical (SOD) and neurotransmitters (Serotonin, Norepinephrine and Dopamine). Results: After extensive investigation, it has been established that Vincamine, alone and in combination with Melatonin, is beneficial in treating depression. Positive results are obtained. The group treated with Vincamine taken per oral route ((10 mg/kg), Melatonin (10 mg/kg), Vincamine + Melatonin (10 mg/kg + 10 mg/kg) and std (10 mg/kg) treatment showed significant result which are followed as for all groups (a) p < 0.0001 vs NC; (b) p < 0.0001 vs disease control; (c) p < 0.05 vs Std (10 mg/kg); (d) p < 0.001V vs M (10 mg/kg); (e) p < 0.0090 vs V+M (10 mg/kg+10 mg/kg). It was demonstrated by a number of behavioral (elevated plus maze, forced swim test, open field test, and sucrose preference test) and biochemical parameters (estimation of neurotransmitters such as serotonin, epinephrine, and dopamine). Vincamine alone and in combination with Melatonin demonstrated positive results (p < 0.0001) in the evaluation of the SOD antioxidant defence system. Also, it significantly attenuated the alteration in locomotor activity, oxidative stress and neurotransmitters in rat brain. result: After extensive investigation, it has been established that Vincamine, alone and in combination with Melatonin, is beneficial in treating depression. Positive results are obtained. The group treated with Vincamine taken per oral route ((10mg/kg), Melatonin (10mg/kg), Vincamine + Melatonin (10mg/kg + 10mg/kg) and std (10mg/kg) treatment showed significant result which are followed as for all groups (a) p < 0.0001 vs NC; (b) p < 0.0001 vs disease control; (c) p < 0.05 vs Std (10 mg/kg); (d) p < 0.001V vs M (10 mg/kg); (e) p < 0.0090 vs V+M (10mg/kg+10mg/kg). It was demonstrated by a number of behavioral (elevated plus maze, forced swim test, open field test, and sucrose preference test) and biochemical parameters (estimation of neurotransmitters such as serotonin, epinephrine, and dopamine). Vincamine alone and in combination with Melatonin demonstrated positive results (p<0.0001) in the evaluation of the SOD antioxidant defence system. Also, significantly attenuated the alteration in locomotor activity, oxidative stress and neurotransmitters in rat brain. Conclusion: It has been concluded that vincamine alone and along with melatonin is effective for the treatment of depression on the basis of behavioural and biochemical parameters. That’s why it might be useful for the future prospect.

Mechanisms of norepinephrine induced calcium responses in perivascular adipocytes

Perivascular adipose tissue (PVAT) has emerged as a key regulator of vascular tone and blood pressure making it an intriguing avenue for research related to pervasive aliments such as high blood pressure. PVAT surrounds the majority of blood vessels where it releases anticontractile factors such as nitric oxide, hydrogen sulfide, adiponectin, and leptin. The production of these anticontractile factors is driven by the sympathetic neurotransmitter norepinephrine (NE), but there is little known about mechanisms which mediate the NE response in PVAT. Based on the known role of beta adrenergic receptors in other fat depots, we hypothesized that NE primarily acts on beta II and III adrenergic receptors. Adiponectin cre positive transgenic mice genetically encoded with calcium indicators were used for live calcium imaging. The peaks of the NE response before and after the receptor antagonists were applied by comparing the change in fluorescence. The beta receptor antagonist, SR 59230A, was used at 6.5μM to block both beta II and III receptors. In addition, the A1a antagonist RS 100329 at 1μM was used to block alpha receptors present. Both antagonists were chosen because they have previously used in the literature successfully at these concentrations. The beta II and beta III antagonist significantly decreased the calcium response in the mesenteric PVAT (p=<0.0001) by 33% and a 27% significant decrease in the subcutaneous fat pad (p=). The alpha 1a antagonist significantly decreased the calcium response in the mesenteric PVAT (p=<0.0001) by 59%, as well as an 86% significant decrease in the subcutaneous fat pad (p=<0.0001), and a 60% significant decrease in the aortic PVAT (p=<0.0001). The combination of both antagonists significantly decreased the calcium response in the mesenteric PVAT (p=<0.0001) by 33%, as well as 46% in the subcutaneous fat pad (p=<0.0001), and 37% decrease in the aortic PVAT (p=0.0354). Both beta and alpha adrenergic receptors are present in mesenteric PVAT and subcutaneous fat, while primarily alpha adrenergic receptors are present in aortic PVAT. These observations suggest the mechanisms responsible for NE induced calcium responses are tissue dependent. HL152951. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The roles of extrinsic neurons in modulating neuroimmune crosstalk during acute enteric infection with Citrobacter rodentium

Background: The intestinal tract is one of the most densely innervated organs in our body, containing extrinsic sensory and sympathetic neurons. With their cell bodies located outside of the gut, these neurons directly detect enteric pathogens and release immunomodulatory neurotransmitters or neuropeptides to communicate with immune cells in the gut. Specifically, sympathetic neurons secrete neurotransmitter norepinephrine, which activate β2 adrenergic receptors (β2ΑR) on immune cells to regulate immune functions. Recent studies from our lab, as well as others, have begun to highlight the neural regulation of immune responses during enteric infections. However, the precise pathways responsible for orchestrating these effects remain elusive. Hypothesis: We sought to determine whether extrinsic sensory and sympathetic neurons are implicated in host protective responses against enteric pathogen Citrobacter rodentium (C. rodentium). Methods: Mice were inoculated by oral gavage with C. rodentium (108 colony-forming units) or sterile luria broth. Bacterial colonization was quantified by homogenization of distal colon tissues and plating serial dilutions onto MacConkey agar. Relevant tissues were collected for qPCR, flow cytometry or histology. Genetically engineered Arc Targeted Recombination in Active Population (TRAP) mice were used to identify neurons that were activated during infection. These ArcTRAP mice received single intraperitoneal (i.p.) injection of 4-hydroxytamoxifen post-infection to “trap” active neurons, marking them tdTomato+. 6-hydroxydopamine (6OHDA) was used to chemically ablate sympathetic innervations to the colon via 3 consecutive daily i.p. injections. Results: At day 4 post-infection, there were significantly more active tdTomato+ neurons in the rostral ventrolateral medulla (RVLM) of the infected mice compared to the non-infected controls. This increase was more pronounced as the infection peaked at day 10, indicating that more neurons were being activated in the RVLM in response to C. rodentium in the gut. 6OHDA treatment significantly increased bacterial burden in distal colon at day 10 post-infection. This was associated with decreased tyrosine hydroxylase expression compared to the vehicle controls. Subsequently, qPCR revealed that there was increased pro-inflammatory cytokines expression in the colon of sympathectomized infected mice compared to the infected controls. Similarly, β2AR knockout significantly increased bacterial burden in distal colon at day 3 and 10 post-infection. Increased pro-inflammatory cytokines expression suggests an immunomodulatory role for β2AR during C. rodentium infection. Conclusions: These studies provided novel insights into the neuroimmune crosstalk that is crucial for acute enteric infections with C. rodentium. Specifically, these experiments may reveal how extrinsic neurons shape local immune responses in the gut. NIH NIAID R01AI150647; Graduate Student Support Program (UC Davis: School of Veterinary Medicine). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

β-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture

The autonomic nervous system plays a crucial role in regulating bone metabolism, with sympathetic activation stimulating bone resorption and inhibiting bone formation. We found that fractures lead to increased sympathetic tone, enhanced osteoclast resorption, decreased osteoblast formation, and thus hastened systemic bone loss in ovariectomized (OVX) mice. However, the combined administration of parathyroid hormone (PTH) and the β-receptor blocker propranolol dramatically promoted systemic bone formation and osteoporotic fracture healing in OVX mice. The effect of this treatment is superior to that of treatment with PTH or propranolol alone. In vitro, the sympathetic neurotransmitter norepinephrine (NE) suppressed PTH-induced osteoblast differentiation and mineralization, which was rescued by propranolol. Moreover, NE decreased the PTH-induced expression of Runx2 but enhanced the expression of Rankl and the effect of PTH-stimulated osteoblasts on osteoclastic differentiation, whereas these effects were reversed by propranolol. Furthermore, PTH increased the expression of the circadian clock gene Bmal1, which was inhibited by NE-βAR signaling. Bmal1 knockdown blocked the rescue effect of propranolol on the NE-induced decrease in PTH-stimulated osteoblast differentiation. Taken together, these results suggest that propranolol enhances the anabolic effect of PTH in preventing systemic bone loss following osteoporotic fracture by blocking the negative effects of sympathetic signaling on PTH anabolism.

Resistance exercising on unstable surface leads to Pupil Dilation

BackgroundChronic resistance training and acute resistance exercises improve physical performance and can enhance cognitive performance. However, there is still uncertainty about the mechanism(s) responsible for cognitive improvement following resistance training and exercise. Recent findings suggest that resistance exercise has metabolic as well as cognitive demands, which potentially activate similar neural circuitry associated with higher-order cognitive function tasks. Exercising on unstable devices increases the coordinative and metabolic demands and thus may further increase cognitive activation during resistance exercise. The measurement of pupil diameter could provide indications of cognitive activation and arousal during resistance exercise. Pupil dilation is linked to the activity in multiple neuromodulatory systems (e.g., activation of the locus coeruleus and the release of the neurotransmitter norepinephrine (LC-NE system)), which are involved in supporting processes for executive control. Therefore, the purpose of this study was to compare the cognitive activation measured by pupil diameter during an acute bout of resistance exercise on stable and unstable surfaces.Methods18 participants (23.5 ± 1.5 years; 10 females) performed ten kettlebell squats in a preferred repetition velocity in stable and unstable (BOSU® Balance Trainer) ground conditions. Pupil diameter was recorded with eye tracking glasses (SMI ETG) during standing (baseline) and during squatting. Raw pupil data were cleaned of artifacts (missing values were linearly interpolated) and subjected to a subtractive baseline correction. A student t-test was used to compare mean pupil diameter between ground conditions.ResultsThe mean pupil diameter was significantly greater during squats in the unstable condition than in the stable condition, t (17) = -2.63, p =.018, Cohen’s dZ = -0.62; stable: 0.49 ± 0.32 mm; unstable: 0.61 ± 0.25 mm).ConclusionAs indicated by pupil dilation, the use of unstable devices can increase the cognitive activation and effort during acute bouts of resistance exercise. Since pupil dilation is only an indirect method, further investigations are necessary to describe causes and effects of neuromodulatory system activity during resistance exercise. Resistance training with and without surface instability can be recommended to people of all ages as a physically and cognitively challenging training program contributing to the preservation of both physical and cognitive functioning.