Nervous System Regulation Research Articles

Heart rate variability modifications in response to different types of exercise training in athletes.

Spectral analysis of heart rate variability (HRV) is a long-standing technique to indirectly assess neural cardiac regulation. This article specifically addressed how spectral analysis of HRV could help to understand neural cardiovascular adaptations to long-term exercise training; and inform us on training status in athletes. We reviewed literature searching for articles investigating resting cardiovascular adaptations to long-term exercise training through spectral analysis of HRV in athletes, from amateur to world class categories, practicing different sport disciplines, and focusing, in particular, on a series of work performed over time in our laboratory, which may highlight how different types of exercise training differently affect neural cardiac regulation. Spectral analysis of HRV has been shown its capability of detecting different adaptational changes in cardiac autonomic nervous system (ANS) regulation attending physical training in athletes of different sport disciplines. Studies showed that spectral analysis of HRV provide results that are sport-dependent and differ at individual level. ANS adaptations to exercise training are presented and discussed. Reported studies indicate that spectral analysis of HRV is an effective tool to monitor and optimize the training process and to predict athletic achievements in competitions. Cardiac ANS adaptations are strongly dependant on the type of training being performed. The individual nature of cardiac ANS adaptations should be considered to properly interpret the observed findings.

The Transcription Factor TFCP2L1 is Associated with Myelination via miR708-5p Regulation in the Peripheral Nerve System

MicroRNAs (miRNAs) have been implicated in nerve injury and demyelination; however, their functions in peripheral nerves remain unclear. To determine the potential functions of miRNAs, an miRNA array was carried out. Here, miRNA array analysis of neuregulin-treated Schwann cells revealed 18 upregulated (> 2-fold) and 13 downregulated (> 2-fold) miRNAs. After sciatic nerve injury, miR708-5p was highly expressed in neuregulin-treated Schwann cells, whereas it was downregulated during postnatal development. A predicted functional interaction was found between miR708-5p and transcription factor CP2-like protein 1 (TFCP2L1) using a bioinformatics tool. This finding suggested that miR708-5p may regulate TFCP2L1. During sciatic nerve development, TFCP2L1 was upregulated on postnatal days 1 and 4, while it was downregulated after nerve axotomy and crush injury. Notably, TFCP2L1 was upregulated in cAMP-treated Schwann cells. We also found that activity of the myelin protein zero promoter was downregulated in TFCP2L1 siRNA-treated Schwann cells, whereas it was upregulated in TFCP2L1-overexpressing cells. Immunofluorescence analysis showed that TFCP2L1 was localized in Schwann cells. In addition, miR708-5p overexpression promoted migration of Schwann cells, while miR-708-5p inhibitor inhibited migration. miR708-5p inhibitor also blocked the migration of TFCP2L1 siRNA-treated Schwann cells. These findings indicate the functions of miR708-5p in TFCP2L1 regulation in the peripheral nervous system occur via regulation of Schwann cell migration.

Treatment of Irritable Bowel Syndrome by Chinese Medicine: A Review.

Irritable bowel syndrome (IBS) is a common refractory disease. Chinese medicine (CM) has remarkable efficacy and advantages on the treatment of IBS. This review summarized the articles focusing on the treatment of IBS with CM to sum up the latest treatment methods for IBS and the underlying mechanisms. Literature analysis showed that prescriptions, acupuncture, and moxibustion are the primary methods of CM treatment for IBS. The potential mechanism centers on the regulation of the enteric nervous system, the alleviation of visceral hypersensitivity, the stability of intestinal flora, and the regulation of the immune system.

Insomnia in Emotional Labor: Its Role in Autonomic Nervous System Regulation.

ObjectiveThe relation between female emotional laborers’ sleep quality and autonomic nervous system activity was investigated. MethodsThirty-three subjects’ heart rate variability (HRV) data and results of self-reported scale on sleep, depression, anxiety and suicidality, were collected. Subjects were classified into good sleeper (GS) and poor sleeper (PS) groups relying on sleep quality. Changes of HRV between working time and resting time in each group were compared. ResultsThe PS group showed significantly lower difference in root mean square of successive differences (RMSSD), percentage of successive normal-to-normal intervals that differ by more than 50 ms (pNN50), and natural logarithm high-frequency (LnHF) when they were working as compared to when they were resting, which means decreased function of the parasympathetic nervous system (PNS). Repeated measures analysis of covariance showed that the group effect was significant only for LnHF, with score of depression scale as a covariate. ConclusionFemale emotional laborers who complain of sleep difficulty may have decreased function of the PNS. Therefore, good sleep quality is essential for maintaining and promoting mental and physical health of women engage in emotional labor.

When triggers become tigers: taming the autonomic nervous system via sensory support system modulation

ABSTRACT Personalized recovery technologies may enable individuals with Substance Use Disorder (SUD) to monitor and manage acute craving and drug use urges in ways that improve drug-seeking decisions in real-time. Direct and indirect regulation of the autonomic nervous system through sensory input monitoring and modulation may enhance control over behavioral decisions and prevent relapse. A personalized sensory support system that monitors neurophysiological reactivity and offers non-pharmacological point-in-time personalized digital interventions may increase awareness of and control over craving reactivity. It is critical to be able to detect these warning signs and intervene early and effectively. The use of wearable technologies that assess point-in-time neurophysiological escalation and shape behavioral responses through personalized interventions could be transformative in allowing individuals to better manage their recovery as they transition out of institutions and move back into community settings.

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Recent Progress in the Understanding of the Effect of Sympathetic Nerves on Hair Follicle Growth.

Clinical observation and experimental studies have long suggested that the perifollicular nerves have nutritional and regulatory effects on the growth, development, and physiological cycle of hair follicles (HFs), even though the concrete mechanism remains obscure. Recently, with the progress of immunohistochemistry and molecular biology techniques, more innovation has been made in the study of the follicular sympathetic nerves and its nerve-effect factor norepinephrine affecting hair follicle stem cells. This review highlights the progress in the regulation of the sympathetic nervous system toward the growth of HFs.

Deletion of C1ql1 Causes Hearing Loss and Abnormal Auditory Nerve Fibers in the Mouse Cochlea.

Complement C1q Like 1 (C1QL1), a secreted component of C1Q-related protein, is known to play an important role in synaptic maturation, regulation, and maintenance in the central nervous system. C1ql1 is expressed in adult cochlear inner and outer hair cells (IHCs and OHCs) with preferential expression in OHCs. We generated C1ql1 null mice to examine the role of C1QL1 in the auditory periphery. C1ql1-null mice exhibited progressive hearing loss with elevated thresholds of auditory brainstem response and distortion product otoacoustic emission. Confocal microscopy showed that the number of nerve fibers innervating both IHCs and OHCs was significantly reduced. However, spiral ganglion neurons appeared to be normal under electron microscopy. IHC development and survival were not affected by deletion of C1ql1. Voltage-clamp recording and immunocytochmistry combined with confocal microscopy showed C1ql1-null IHCs showed no significant reduction of pre-synaptic proteins and synaptic vesicle release. This is in contrast to significant OHC loss in the KO mice. Our study suggests that C1ql1 is essential for development of hair cell innervation and OHC survival. But maturation of presynaptic machinery in IHCs does not depend on C1QL1.

FMR1 and Autism, an Intriguing Connection Revisited.

Autism Spectrum Disorder (ASD) represents a distinct phenotype of behavioral dysfunction that includes deficiencies in communication and stereotypic behaviors. ASD affects about 2% of the US population. It is a highly heritable spectrum of conditions with substantial genetic heterogeneity. To date, mutations in over 100 genes have been reported in association with ASD phenotypes. Fragile X syndrome (FXS) is the most common single-gene disorder associated with ASD. The gene associated with FXS, FMR1 is located on chromosome X. Accordingly, the condition has more severe manifestations in males. FXS results from the loss of function of FMR1 due to the expansion of an unstable CGG repeat located in the 5′′ untranslated region of the gene. About 50% of the FXS males and 20% of the FXS females meet the Diagnostic Statistical Manual 5 (DSM-5) criteria for ASD. Among the individuals with ASD, about 3% test positive for FXS. FMRP, the protein product of FMR1, is a major gene regulator in the central nervous system. Multiple pathways regulated by FMRP are found to be dysfunctional in ASD patients who do not have FXS. Thus, FXS presents the opportunity to study cellular phenomena that may have wider applications in the management of ASD and to develop new strategies for ASD therapy.

The Response To Physical Activity In Mouse And Man: An Interplay Between Genetics And Exercise

Increased physical activity is routinely prescribed by physicians as a defense to combat and prevent cardiometabolic diseases. Despite this, the molecular mechanisms by which participation in physical activity leads to improvements in health are unknown and needed for the development of personalized medicine and next generation therapeutic approaches. To address these needs, we undertook an unprecedented massive scale genetics project where female mice from the Hybrid Mouse Diversity Panel (HMDP) performed voluntary wheel running for approximately one month. The HMDP is a powerful and unique genetic tool that has been used in the intricate dissection of complex traits, especially cardiometabolic ones, and consists of over 100 inbred and recombinant inbred strains of mice. Twelve samples were taken from each animal resulting in thirty different traits allowing for a comprehensive whole-body and tissue specific assessment of the exercise response to be conducted. Furthermore, our exercise HMDP was integrated with the human Skeletal Muscle, Myokines and Glucose Metabolism (MyoGlu) study. This study consisted of twenty-six normal or overweight male Norwegians who were subjected to a 12-week exercise training program with pre- and post-acute exercise bouts. Subcutaneous white adipose tissue and skeletal muscle biopsies were taken at multiple time points within MyoGlu which nicely complement, substantiate, and expound upon our mouse data. Using a multi-tissue and multi-omics approach in mouse and man, our discoveries fit into four main categories: 1) phenotypic response to exercise for clinically and physiologically relevant traits (highlighted by reductions in liver triglycerides), 2) molecular response to exercise within skeletal muscle, white adipose tissue, brown adipose tissue, liver, and heart (distinct reprogramming of brown adipose tissue metabolism), 3) a personalized exercise response due to the interaction between exercise dose (duration, intensity, type) and natural genetic variation, and 4) insight into the biology of volitional exercise where strong central nervous system regulation was uncovered. Our results are also being made publicly available in a user friendly and simple web app designed to allow researchers to visualize, compare, and interrogate data at all levels.

Developmental regulation and lateralization of N-methyl-d-aspartate (NMDA) receptors in the rat hippocampus

N-methyl-d-aspartate receptors (NMDARs) are expressed abundantly in the brain and play a crucial role in the regulation of central nervous system (CNS) development, learning, and memory. During early neuronal development, NMDARs modulate neurogenesis, neuronal differentiation and migration, and synaptogenesis. The present study aimed to examine the developmental expression of NMDARs subunits, NR1 and NR2B, in the developing hippocampus of neonatal rats during the first two postnatal weeks. Fifty-four male offspring were randomly divided into three age groups, postnatal days (P) 0, 7, and 14. Real-time-PCR, western blotting, and immunohistochemistry (IHC) analyses were employed to examine and compare the hippocampal expression of the NMDA receptor subunits. The highest mRNA expression of NR1 and NR2B subunits was observed at P7, regardless of its laterality. The mRNA expression of both subunits in the right hippocampus was significantly higher than that of the left one at P0 and P7. Similarly, the highest protein level expression of NR1 and NR2B subunits was also observed at P7 in both sides hippocampi. Although the protein expression of NR1 was significantly higher on the right side in all studied days, the NR2B was significantly higher in the right hippocampus only at P7. The analysis of optical density (OD) has shown a marked increase in the distribution pattern of the NR1 and NR2B subunits at P7 in all hippocampal subregions. In conclusion, there is a marked right-left asymmetry in the expression of NR1 and NR2B subunits in the developing rat hippocampus, which might be considered as a probable mechanism for the lateral differences in the structure and function of the hippocampus in rats.

Sleep quality and associated factors among patients with chronic illness at South Wollo Zone Public Hospitals, Northeast Ethiopia

Background: Pathological and nighttime sleep deprivations have substantial adverse effects on regulation of weight, sugar and blood pressure because of endothelial dysfunction, sympathetic nervous system stimulation, regulation and activation of systemic inflammation. Thus, this study was aimed to assess quality of sleep among patients with chronic illness and its associated factors at South Wollo Zone Public Hospitals, Northeast Ethiopia. Methods and Materials: The study was conducted at South Wollo Zone Public Hospitals, Northeast Ethiopia from February 15 2019 till April 15 2019. Institutional based cross sectional study design was employed. All patients with chronic illness who are on follow up in South Wollo Zone Public Hospitals were sources of population. Sample size was calculated by using EPI info version 7 and the total sample size was 344. The study employed stratified random sampling technique and study participants were selected by systematic sampling. After taking ethical approval from College of Medicine and Health Sciences Ethical Approval Committee, permission from selected Hospitals and informed verbal consent from patients, the data were collected by a tool which has 3 parts: Sociodemographic data, Pittsburgh Sleep Quality Index and factors affecting sleep quality. Data were entered in to Epi data version 4.1 and exported to Statistical Package for Service Product 25 for analysis. Different data presentation tools and binary logistic regression were enrolled by considering 95% confidence level and p value of 0.05. Result: Among the total study participants, near to one third (31.7%) of them got sleep after 30 minutes. More than one fourth of them slept for less than 7 hours. Less than half of the study participants had habitual sleep efficiency of more than 85% however 296(86%) of them did not face day time dysfunction Conclusion and recommendations: more than one third of patients with chronic illness had poor sleep quality. One third of study participants had sleep duration of less than the recommendations(less than 7 hours). Age, educational status, residence, and perception of prognosis of disease were factors that have associations with poor sleep quality among patients with chronic illness. Health care providers who are doing in chronic illness follow up clinic should be initiated to assess and screen those patients with poor sleep quality.

Defining a Role for G-Protein Coupled Receptor/cAMP/CRE-Binding Protein Signaling in Hair Follicle Stem Cell Activation

Manipulation of adrenergic signaling has been shown experimentally and clinically to affect hair follicle growth. In this study, we provide direct evidence that canonical cAMP/CRE-binding protein signaling through adrenergic receptors can regulate hair follicle stem cell (HFSC) activation and hair cycle. We found that CRE-binding protein activation is regulated through the hair cycle and coincides with HFSC activation. Both isoproterenol and procaterol, agonists of adrenergic receptors, show the capacity to activate the hair cycle in mice. Furthermore, deletion of ADRB2 receptor, which is thought to mediate sympathetic nervous system regulation of HFSCs, was sufficient to block HFSC activation. Downstream, stimulation of adenylyl cyclase with forskolin or inhibition of phosphodiesterase to increase cAMP accumulation or direct application of cAMP was each sufficient to promote HFSC activation and accelerate initiation of hair cycle. Genetic induction of a Designer Receptors Exclusively Activated by Designer Drug allele showed that G-protein coupled receptor/GαS stimulation, specifically in HFSCs, promoted the activation of the hair cycle. Finally, we provide evidence that G-protein coupled receptor/CRE-binding protein signaling can potentially act on HFSCs by promoting glycolytic metabolism, which was previously shown to stimulate HFSC activation. Together, these data provide mechanistic insights into the role of sympathetic innervation on HFSC function.

Changes in autonomic tone during delirium in acute stroke patients assessed by pupillometry and skin conductance

Delirium is a common complication in acute ischemic stroke, possibly caused by alterations in the regulation of the sympathetic autonomic nervous system. We investigated whether such an association could be demonstrated with two easy-to-use measurement techniques: Measurement of palmar skin conductance level (SCL) and pupillometry measuring the dilation velocity in the pupillary light reflex (PLRdil.vel.).The cohort study included 64 patients admitted with acute ischemic stroke. During the study period (median 4.1 days, interquartile range 2.1 days) patients were assessed for delirium once daily as well as with measurements of SCL and PLRdil.vel up to twice daily. SCL and PLRdil.vel. during delirium were lower than without delirium present. For SCL the unadjusted difference was −40.8% (95% CI (−55.1 to −22.0), P value <.001) and for PLRdil.vel the unadjusted difference was −0.22 mm/s (95% CI (−0.42 to −0.01), P value = .041). The results demonstrate changes in sympathetic autonomic nervous system regulation during delirium in acute stroke patients.

Regulation of the Autonomic Nervous System on Intestine.

Intestine is composed of various types of cells including absorptive epithelial cells, goblet cells, endocrine cells, Paneth cells, immunological cells, and so on, which play digestion, absorption, neuroendocrine, immunological function. Intestine is innervated with extrinsic autonomic nerves and intrinsic enteric nerves. The neurotransmitters and counterpart receptors are widely distributed in the different intestinal cells. Intestinal autonomic nerve system includes sympathetic and parasympathetic nervous systems, which regulate cellular proliferation and function in intestine under physiological and pathophysiological conditions. Presently, distribution and functional characteristics of autonomic nervous system in intestine were reviewed. How autonomic nervous system regulates intestinal cell proliferation was discussed. Function of autonomic nervous system on intestinal diseases was extensively reviewed. It might be helpful to properly manipulate autonomic nervous system during treating different intestinal diseases.

Metabolomic and transcriptomic analysis reveals endogenous substrates and metabolic adaptation in rats lacking Abcg2 and Abcb1a transporters.

Abcg2/Bcrp and Abcb1a/Pgp are xenobiotic efflux transporters limiting substrate permeability in the gastrointestinal system and brain, and increasing renal and hepatic drug clearance. The systemic impact of Bcrp and Pgp ablation on metabolic homeostasis of endogenous substrates is incompletely understood. We performed untargeted metabolomics of cerebrospinal fluid (CSF) and plasma, transcriptomics of brain, liver and kidney from male Sprague Dawley rats (WT) and Bcrp/Pgp double knock-out (dKO) rats, and integrated metabolomic/transcriptomic analysis to identify putative substrates and perturbations in canonical metabolic pathways. A predictive Bayesian machine learning model was used to predict in silico those metabolites with greater substrate-like features for either transporters. The CSF and plasma levels of 169 metabolites, nutrients, signaling molecules, antioxidants and lipids were significantly altered in dKO rats, compared to WT rats. These metabolite changes suggested alterations in histidine, branched chain amino acid, purine and pyrimidine metabolism in the dKO rats. Levels of methylated and sulfated metabolites and some primary bile acids were increased in dKO CSF or plasma. Elevated uric acid levels appeared to be a primary driver of changes in purine and pyrimidine biosynthesis. Alterations in Bcrp/Pgp dKO CSF levels of antioxidants, precursors of neurotransmitters, and uric acid suggests the transporters may contribute to the regulation of a healthy central nervous system in rats. Microbiome-generated metabolites were found to be elevated in dKO rat plasma and CSF. The altered dKO metabolome appeared to cause compensatory transcriptional change in urate biosynthesis and response to lipopolysaccharide in brain, oxidation-reduction processes and response to oxidative stress and porphyrin biosynthesis in kidney, and circadian rhythm genes in liver. These findings present insight into endogenous functions of Bcrp and Pgp, the impact that transporter substrates, inhibitors or polymorphisms may have on metabolism, how transporter inhibition could rewire drug sensitivity indirectly through metabolic changes, and identify functional Bcrp biomarkers.

MUSCULOSKELETAL TRAINING AND MECHANICAL CHARACTERISTICS OF ATHLETES

ABSTRACT Introduction: Studying the biomechanical characteristics of lower limb muscles during depth jumps is of great significance, but it is also important in meeting the practical needs of strength training. Objective: To explore the musculoskeletal exercise training and mechanical characteristics of athletes’ lower limbs. Methods: Analysis and discussion of the test results of kinematics, dynamics and the EMG of 8 muscles of the lower extremity when athletes jump at different falling heights and different motion states. Results: only by using different falling heights in a certain proportion can training efficiency be improved and the training effect of depth jumps reach the practical purpose of sports training. Conclusions: from the point of view of exercise physiology, the generation, storage and reuse of muscle elastic deformation energy and the reflex regulation of the central nervous system are the main reasons for the economic and efficient contractive ability of the extensor muscle group of lower limbs during depth jumps. From the point of view of muscle mechanical properties, the centrifugal contractility of lower limb muscles is the primary factor that determines the athletes’ lower limb muscle explosive push ability. Level of evidence II; Therapeutic studies - investigation of treatment results.

T-cell infiltration, contribution and regulation in the central nervous system post-traumatic injury.

T cells participate in the repair process and immune response in the CNS post‐traumatic injury and play both a beneficial and harmful role. Together with nerve cells and other immune cells, they form a microenvironment in the CNS post‐traumatic injury. The repair of traumatic CNS injury is a long‐term process. T cells contribute to the repair of the injury site to influence the recovery. Recently, with the advance of new techniques, such as mass spectrometry‐based flow cytometry, modern live‐cell imaging, etc, research focusing on T cells is becoming one of the valuable directions for the future therapy of traumatic CNS injury. In this review, we summarized the infiltration, contribution and regulation of T cells in post‐traumatic injury, discussed the clinical significance and predicted the future research direction.

DECODING THE GENE EXPRESSION PROGRAM EVOLVED IN ODONTOGENIC KERATOCYST BY THE COMBINATION OF DEEP TRANSCRIPTOMICS ANALYSES AND COMPUTATIONAL BIOLOGY TOOLS

<h3>Background</h3> <i>Transcriptomics</i> analysis of odontogenic keratocysts (OKCs) has been described in 3 microarray-based studies utilizing fresh-frozen or formalin-fixed paraffin-embedded samples. To date, RNA-sequencing (RNA-seq) technology has been applied only for the transcriptomics analysis of OKC-derived fibroblasts. <h3>Objective</h3> RNA-seq analysis of the entire OKC tissue will enable the identification of the gene expression profile that accompanies OKC development. <h3>Methods</h3> Total RNA was extracted from formalin-fixed paraffin-embedded samples of 3 OKCs and 3 dental follicles of third molars. RNA library preparation and 150-bp paired-end sequencing were implemented using an Illumina Hiseq4000 Sequencer followed by application of advanced computational biology tools; for example, edgeR software package and Galaxy platform. <h3>Results</h3> RNA-sequencing resulted in ∼15 to 40 million paired-end reads per sample. A total of 1335 differentially expressed genes (DEGs) between OKCs and dental follicles (fold change ≥2) were captured. Gene ontology classification analysis identified markers of epidermal cell development and differentiation (e.g., DSP, TFAP2A, FOXM1) among the top upregulated DEGs, markers of extracellular matrix organization and nervous system regulation (e.g., ADAMTS14, COL3A1, NAV3), among the top downregulated DEGs, and various transcription factors in both categories exemplified by the upregulation of the epidermal master regulator TP63 in OKCs. <h3>Conclusions</h3> This is the first RNA-seq-based study of the entire OKC. The preliminarily results show significant upregulation of genes commuting to epidermis development/differentiation, a finding consistent with OKC histopathologic phenotype. The identification of novel DEGs is critical to access unknown elements of the molecular mechanism underlying OKC pathogenesis and biologic behavior, with potential for future therapeutic applications.

Exercise-Induced MicroRNA Regulation in the Mice Nervous System is Maintained After Activity Cessation.

Physical exercise can improve synaptic function and protect the nervous system against many diseases by altering gene regulation. MicroRNAs (miRs) have emerged as vital regulators of gene expression and protein synthesis not only in the muscular system, but also in the brain. Here we investigated whether exercise-induced miRs expression in the nervous and muscular systems is activity-dependent or it remains regulated even after exercise cessation. The expression profile of miR-1, -16, and -206 was monitored by RT-PCR in the dorsal root ganglion, in the spinal cord dorsal and ventral horn, and in the soleus muscle of mice after 5 weeks of swimming training and after swimming exercise followed by 4 weeks of sedentary conditions. Control animals consisted of mice that swan daily for 30s during the 5-weeks training period, returning to the non-swimming activity for additional 4 weeks. After exercise, miR-1 was upregulated in all tissues investigated. However, the upregulation of miR-1 continued significantly high in both aspects of the spinal cord and in the soleus muscle. The expression profiles of miR-16, and -206 were increased only in the nervous system. However, miR-16 upregulation persisted in the DRG and in the spinal cord after exercise interruption, whereas miR-206 continued upregulated only in the spinal cord ventral horn. Exercise training can cause long-lasting changes in the expression of miRs independently of exercise maintenance. Spatial and temporal expression of miRs is to some extent dependent on this activity. The data raised a new conceptual hypothesis on the biogenesis of miRs, indicating that long-lasting and systematic exercise can potentially cause irreversible miR regulation after activity cessation.