Autonomic Nervous Dysfunction Research Articles

Peripheral neuropathy in Parkinson's disease.

Peripheral neuropathy (PN) is a common neurological problem defined as a dysfunction of sensory, motor, and autonomic nerves. The presence of peripheral neuropathy has recently been noticed in Parkinson's disease (PD) This comorbidity is concerning as it increases the burden on patients whose motor functions are previously compromised. A comprehensive computer-based literature review utilizing multiple peer-reviewed databases (e.g., Embase, PsycINFO, CINAHL, etc.) was conducted. There is evidence for the utility of robust diagnostic criteria to distinguish between large fiber neuropathy (LFN) and small fiber neuropathy (SFN). Some studies have established links between prolonged L-DOPA exposure and prevalence with increased levels of homocysteine (HCY) and methylmalonic acid (MMA) as pathological underlying mechanisms. PN in PD patients with relatively truncated exposure to L-DOPA therapy may have underlying mutations in the Parkin and MHTFR gene or separate mitochondrial disorders. Vitamin B12 and cobalamin deficiencies have also been implicated as drivers of PN. Accumulation of phosphorylated α-synuclein is another central feature in PN and deems urgent exploration via large cohort studies. Importantly, these underlying mechanisms have been linked to peripheral denervation. This review delves into the potential treatments for PN targeting B12 deficiencies and the use of COMT inhibitors along with other novel approaches. Avenues of research with powerful randomized controlled and long-term cohort studies exploring genetic mechanisms and novel treatment pathways is urgently required to alleviate the burden of disease exerted by PN on PD.

Assessment of autonomic dysfunction between type I and type II diabetes mellitus

Introduction: The diabetes is the most common disease in the present world and India is country with highest incidence of Diabetes Mellitus in the world. The autonomic nervous dysfunction due to diabetes is the common complication of the diabetes. In this study autonomic dysfunction in pateints with type I and type 2 DM and its correlation with the duration of diseases is studied. Materials and Methods: The study was conducted on 30 type I diabetic patients and 40 type II diabetic pateints. All the diabetic patients were questioned about the presence of symptoms reported to be related to autonomic neuropathy. The conventional autonomic function tests were performed on all the subjects inclusive of sympathetic and parasympathetic tests. The scoring of positive and negative for autonmomic dysfuntion was done. Results: The duration of disease in type 1 diabetes, was 6 to 15 years and in type 2 diabetes it was 8 to 18 years with mean duration of 8.5 and 14 years respectively. The mean HbA1C in type 1 DM was 6.21±2.09 and it was 7.50±2.45 in type 2 DM. Comparison of autonomic function tests in the form of heart rate and BP response in subjects with type 1 and type 2 showed that there no significant statistical difference between the groups. Conclusion: It can be concluded the presence of autonomic dysfunction in type 1 and type 2 diabetes mellitus might be due to nerve damage. The duration of diabetes is directly related to such autonomic dysfunction. Keywords: Diabetes Mellitus type 1, Diabetes Mellitus type 2, Autonomic Functions Tests.

The Association of Autonomic Nervous System Function With Ischemic Stroke, and Treatment Strategies.

Acute ischemic stroke, especially minor stroke, and transient ischemic attack have high risks of recurrence and exacerbation into severe ischemic strokes. It remains challenging to perform risk stratification and screen high-risk groups for initiation of early treatment in these patients. Moreover, with the growing population of patients with chronic small vessel disease, the mechanisms and clinical implications require further investigation. Traditional tools such as the ABCD2 score (age, blood pressure, clinical features, duration of symptoms, diabetes) have only moderate predictive value in patients with transient ischemic attack or minor stroke. By contrast, measurement of changes in heart rate variability (HRV) is an important and novel tool for risk stratification and outcome prediction in patients with cardiovascular diseases, as it reflects the overall level of autonomic nervous system dysfunction. Thus, abnormal HRV may be useful for prognosis and improve stratification of stroke patients with diverse risks. HRV may also partially explain autonomic nervous dysfunction and other manifestations during the process of chronic cerebral small vessel disease. In summary, measurement of HRV may contribute to early initiation of interventions in acute or chronic stroke patients using novel treatments involving rebalancing of autonomic nervous system function.

Comparison of Tp-e interval, QTc interval and Tp-e/QTc ratios between non-diabetic and prediabetic population

Aim: Increased blood glucose concentration and cardiac autonomic nerve dysfunction are associated with an increased risk of malignant ventricular arrhythmia. Tp-e interval, Tp-e/QT, and Tp-e/QTc are novel parameters used to assess ventricular arrhythmogenicity. This study aimed to compare these parameters with the healthy control group in prediabetics. Materials and Methods: The ECGs of 58 prediabetic patients (29 male, 59.74 ±13.25 years) were examined and matched with the ECGs of 59 healthy controls (28 male, 61.75 ± 12.66 years) that were matched with gender, age and body mass index. From the 12-lead ECG Tp-e and QT intervals were measured and by Bazett's formula QTc was calculated. Tp-e/QT and Tp-e/QTc proportions were also determined. Results: In prediabetic patients, the mean Tp-e interval was significantly longer than the control group (79.07 ± 8.17 vs 72.03 ± 9.77 ms, respectively; p 0.001). Also in prediabetic, Tp-e/QT and Tp-e/QTc were significantly higher than the controls (respectively 0.21 ± 0.25 vs 0.19 ± 0.03 and 0.19 ± 0.02 vs 0.17 ± 0.02; p 0.001). Other ECG parameters were similar in both groups. HbA1c levels and glucose levels were positively correlated with Tp-e / QT and Tp-e / QTc.Conclusion: Prediabetes increases the risk of ventricular arrhythmogenesis by increasing the transmural dispersion of repolarization. The addition of Tp-e interval and TP-e / QT measurements to the routine ECG evaluation of prediabetic patients can be used to predict arrhythmia risk.

Impact of Slow breathing exercise on heart rate variability in male Type 2 diabetes mellitus

Background: Reduced heart rate variability (HRV) with cardiac autonomic nerve dysfunction has been found in Type 2 Diabetes Mellitus (T2DM) patients. Yoga based slow breathing exercise (SBE) improved this autonomic functions in healthy subjects.
 Objectives: To assess the effect of SBE on cardiac autonomic nerve function(CANF) by power spectral analysis of HRV in patients with T2DM.
 Methods: This prospective interventional study was carried on 30 male diagnosed T2DM patients aged 45-55 years with disease duration 5-10 years enrolled from Out Patient Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Dhaka. They performed SBE for 30 minutes twice daily for 3 months. Thirty apparently healthy age, BMI matched male who did not undergo any type of exercise were included as control. To assess the cardiac autonomic nerve function, power spectral analysis of HRV of all patients were done before and after 3 months of SBE. HRV data were recorded by polyrite D (RMS India). For statistical analysis, independent sample and paired sample t-test were used.
 Results: The preintervention values of Low frequency (LF) normalized unit(nu) and Low frequency/High frequency( LF/HF) ratio were significantly (p<0.001) higher and the values of LF power, HF power, HF normalized unit (HF nu) were significantly (p<0.001) lower in all diabetic patients compared to control. The postintervention values of LF power, HF power, HF nu increased significantly (p<0.001) and the LF nu, LF/HF ratio decreased significantly (p<0.001)compared to their pre-intervention values in T2DM. There were no significant differences between the post intervention values of LF nu, HF nu and LF/HF ratio in T2DM and the control.
 Conclusion: Impaired cardiac autonomic nerve function was significantly improved by SBE in T2DM.
 J Bangladesh Soc Physiol. 2019, December; 14(2): 63-68

Metoprolol prevents neuronal dendrite remodeling in a canine model of chronic obstructive sleep apnea.

Obstructive sleep apnea (OSA) is closely associated with central nervous system diseases and could lead to autonomic nerve dysfunction, which is often seen in neurodegenerative diseases. Previous studies have shown that metoprolol prevents several chronic OSA-induced cardiovascular diseases through inhibiting autonomic nerve hyperactivity. It remains unclear whether chronic OSA can lead to dendritic remodeling in the brain, and whether metoprolol affects the dendritic remodeling. In this study we investigated the effect of metoprolol on dendrite morphology in a canine model of chronic OSA, which was established in beagles through clamping and reopening the endotracheal tube for 4 h every other day for 12 weeks. OSA beagles were administered metoprolol (5 mg· kg−1· d−1). The dendritic number, length, crossings and spine density of neurons in hippocampi and prefrontal cortices were assessed by Golgi staining. And the protein levels of hypoxia-inducible factor-1α (HIF-1α) and brain-derived neurotrophic factor (BDNF) were measured by Western blotting. We showed that chronic OSA successfully induced significant brain hypoxia evidenced by increased HIF-1α levels in CA1 region and dentate gyrus of hippocampi, as well as in prefrontal cortex. Furthermore, OSA led to markedly decreased dendrite number, length and intersections, spine loss as well as reduced BDNF levels. Administration of metoprolol effectively prevented the dendritic remodeling and spine loss induced by chronic OSA. In addition, administration of metoprolol reversed the decreased BDNF, which might be associated with the metoprolol-induced neuronal protection. In conclusion, metoprolol protects against neuronal dendritic remodeling in hippocampi and prefrontal cortices induced by chronic OSA in canine.

The Risk Factors for Asymptomatic Pyuria Among Patients With Type 2 Diabetes

Background: Diabetic patients often develop urinary tract infections (UTI). Diabetic patients are also likely to develop mental illness, and psychotropic drugs have anticholinergic adverse effects such as urinary disturbance. We aimed to elucidate the risk factors of asymptomatic pyuria in patients with type 2 diabetes. Methods: We picked up outpatients with type 2 diabetes who visited the Department of Internal Medicine for the first time, from December 2010 to November 2012 for the treatment of diabetes and completed the questionnaire to obtain the medical history. We obtained clinical information from medical records and questionnaires. Urine leukocytes >= 10/high-power field was defined as pyuria. Comparisons such as pyuria group vs. non-pyuria group and non-mental illness group vs. mood disorder group vs. schizophrenia group were performed. Results: One hundred twenty-one patients were eligible. Sixty-nine were males, 52 were females, mean age was 63 years. There were 48 patients who had mental illness. The duration of diabetes was 5.1 years, hemoglobin A1c (HbA1c) was 8.5%. Prevalence of pyuria was 15.7%. Mean age in non-pyuria group was 62.8 years old, and 65.1 years old in pyuria group. Proportion of female (84%) in pyuria group was significantly higher than non-pyuria group. Patients with pyuria significantly more often had mental illness and psychotropic drugs prescription than patients without pyuria. Duration of diabetes in non-pyuria group was 5.3 years and that in pyuria group was 4.0 years. Coefficient of variations of R-R intervals (CVR-R) in electrocardiogram (ECG), an index of autonomic nervous dysfunction, was 3.2% in non-pyuria group and 1.8% in pyuria group. Pyuria group had significantly higher prevalence of autonomic nervous dysfunction. Coexistence of mental illness and lower CVR-R were associated with risk of pyuria in female diabetic patients. Conclusions: In addition to female sex, autonomic neuropathy and mental illness were significant risk factors for pyuria in patients with type 2 diabetes. To elucidate this association, further studies, preferably with larger numbers of subjects, will be needed. J Endocrinol Metab. 2019;9(6):193-198 doi: https://doi.org/10.14740/jem629

Focusing on the functional dry eye

Dry eye is one of the most common eye diseases characterized by disturbance of tear film homeostasis and a series of ocular discomforts. Discrepancy of ocular subjective symptoms and objective signs, especially unexplained severe symptoms without visible signs has been a long-time confusion for ophthalmologists. Functional disorder is a medical condition that impairs normal functioning of bodily processes due to autonomic nervous dysfunction caused by cerebral cortical dysfunction, but at the exterior, there is no appearance of abnormality. Clinical manifestations are the disease symptoms with a lack of exact physical signs and examination results to confirm the diagnosis. According to the definition and characteristics of functional disorder, we put forward the concept of functional dry eye. We assume that those patients with dry eye symptoms but without detectable signs could be classified into such a functional dry eye subtype. The possible mechanism, clinical manifestations, and treatment strategies are further discussed. (Chin J Ophthalmol, 2019, 55: 885-890).

Research on the clinical effect of Jiuwei-Zhenxin granules and buspirone hydrochloride tablets for geriatric anxiety patients

Objective To investigate the clinical efficacy of Jiuwei-Zhenxin granules and buspirone hydrochloride tablets for geriatric anxiety patients. Methods A total of 136 elderly anxiety patients who met the inclusion criteria were randomly divided into two groups with 68 patients in each group. Patients in the control group were treated with butyrocyclone hydrochloride tablets, while the patients in the treatment group were treated with Jiuwei-Zhenxin granules on the basis of control group. Both groups were treated for 4 weeks. The average R-R interval standard deviation at 24 h (SDNN), the standard deviation of the mean normal R-R interval value for every 5 minutes in 24 h (SDANN) and mean square root of inter-period difference between adjacent R-R at 24h (RMSSD) were measured by heart rate variation analyzer. The 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA) were detected using ELISA. The HAMA scale was used to evaluate anxiety and adverse reactions. Results After treatment, the SDNN (132.04 ± 30.17 ms vs. 107.23 ± 23.44 ms, t=16.901), RMSSD (70.12 ± 21.85 ms vs. 46.43 ± 20.09 ms, t=20.367) and SDANN (136.45 ± 27.18 ms vs. 125.62 ± 20.92 ms, t=6.945) of the treatment group were significantly higher than those of the control group (P<0.01). The serum 5-HT (119.69 ± 10.24 ng/L vs. 142.26 ± 13.71 ng/L, t=21.523), NE (126.47 ± 20.15 ng/L vs. 205.84 ± 23.12 ng/L, t=35.776), DA (130.12 ± 15.95 ng/ml vs. 156.47 ± 15.09 ng/ml, t=14.198) were significantly lower than those of the control group (P<0.01). The HAMA scores of the treatment group at week 1, 2, 3 and 4 after treatment were significantly lower than those of the control group (t=2.105, 4.116, 4.270, 3.369, P<0.05). Conclusions The Jiuwei-Zhenxin granules combined with buspironone hydrochloride tablets can reduce the anxiety of elderly anxiety patients, and its mechanism may be related to regulating the body's neurotransmitter to inhibit autonomic nervous dysfunction and reduce anxiety. Key words: Anxiety disorders; Aged; Jiuwei-Zhenxin granules; Butyrocyclosterone hydrochloride tablets; Receptors, neurotransmitter; Heart rate

Autonomic nerve dysfunction and impaired diabetic wound healing: The role of neuropeptides.

Lower extremity ulcerations represent a major complication in diabetes mellitus and involve multiple physiological factors that lead to impairment of wound healing. Neuropeptides are neuromodulators implicated in various processes including diabetic wound healing. Diabetes causes autonomic and small sensory nerve fibers neuropathy as well as inflammatory dysregulation, which manifest with decreased neuropeptide expression and a disproportion in pro- and anti- inflammatory cytokine response. Therefore to fully understand the contribution of autonomic nerve dysfunction in diabetic wound healing it is crucial to explore the implication of neuropeptides. Here, we will discuss recent studies elucidating the role of specific neuropeptides in wound healing.

Autonomous dysfunction and musculoskeletal therapeutic approach

자율 신경계는 다양한 외적 환경의 변화에 대하여 내적 환경을 일정하게 유지하는 항상성을 위하여 내장 기관의 기능을 통합 조절한다. 자율 신경계 조절의 원심 성분인 교감 신경과 부교감 신경은 내장 기관과 신체의 감각 기관으로부터 일반적인 구심성 감각 신경에 의하여 되먹이 기전으로 조절된다. 교감 신경은 일정한 체온을 조절 하기 위한 방법으로 혈액의 재분배 역할을 담당한다. 척추 주변에서 부과되는 많은 힘에 맞서는 척추안정성은 근골격계 통증뿐만 아니라, 척추 신경이 감각, 운동, 자율 신경으로 구성된 점을 고려한다면, 나아가서 신체화 증상에 해당하는 다양한 증상과 서로 연결된다. 오랫동안 근 골격계 스트레스, 급격한 육체적 일을 한 후의 피로, 두통, 소화 불량, 식은 땀, 몸살과 같은 신체 증상들은 이에 해당하는 척추 주변에서 나오는 자율 신경의 분절과 연결된 다. 척추 주변 근골격계의 척수 신경 압박과 견인이 자율 신경 부전의 원인이 될 수 있으며, 자율 신경 부전으로 발생하는 증상을 척추 주변 근골격계 접근으로 치료할수 있다.The autonomic nervous system integrates the functions of the internal organs for the homeostasis to keep the internal environment against various external environmental changes. The sympathetic and parasympathetic nerves are regulated by brain-feedback system of the general afferent sensory nerves from the internal organs and body sensory organs. The sympathetic nervous system plays a role in blood redistribution as a way to regulate constant body temperature. The spinal stability that confronts the many forces imposed on musculoskeletal system is linked to the various symptoms of psycho-somatization, taking into account not only musculoskeletal pain but also the sensory, motor and autonomic nerves of the spinal nerves. Physical symptoms such as long-term musculoskeletal stress, fatigue, headache, dyspepsia, cold sweats, and body aches after acute physical work are associated with the autonomic nervous segments coming from the corresponding spinal segments. Sympathetic nerve compression and traction around the vertebral foramen by the musculoskeletal structure can be the cause of autonomic nerve dysfunction, and the symptoms caused by autonomic dysfunction can be improved by a musculoskeletal approach.

Influence of Vitamin B12 Deficiency on Autonomic Nervous System Activity in Children

: Vitamin B12 has an important role in neuronal development of children. Autonomic nervous dysfunction which can be hidden by compensating mechanisms also accompanies vitamin B12 deficiency. However, in children, there is still limited data about this effect of vitamin B12 deficiency. The aim of this study was to evaluate the autonomic activity in vitamin B12 deficient children by analyzing the heart rate variability (HRV) with Holter monitoring. HRV parameters of 37 children who were diagnosed with vitamin B12 deficiency were compared those of 25 age and sex matched healthy controls. All of the heart rate variability parameters (time-domain and frequency-domain) were reduced in the vitamin B12 deficient group compared with controls. The search for factors modifying heart rate variability yielded that serum vitamin B12 level was significantly effective on both time-domain and frequency-domain HRV parameters. A positive correlation was also found between vitamin B12 levels and the mean of the 5 minute RR interval standard deviations (SDNNi), the square root of the mean of the squared differences of two consecutive RR intervals (RMSSD), low-frequency power (LF) parameters (P < 0.05, r: 0.285, 0.262, 0.246, respectively). In conclusion, vitamin B12 deficiency can cause autonomic dysfunction in children.

Soluble Prorenin Receptor Increases Blood Pressure in High Fat-Fed Male Mice.

Obesity-related hypertension is a major public health concern. We recently demonstrated that plasma levels of the soluble form of the prorenin receptor (sPRR) were elevated in obesity-associated hypertension. Therefore, in the present study, we investigated the contribution of sPRR to blood pressure (BP) elevation in the context of obesity. High fat-fed C57BL/6 male mice were infused with vehicle or sPRR (30 µg/kg per day) via subcutaneously implanted osmotic minipump for 4 weeks. BP parameters were recorded using radiotelemetry devices. Male mice infused with sPRR exhibited higher systolic BP and mean arterial pressure and lower spontaneous baroreflex sensitivity than mice infused with vehicle. To define mechanisms involved in systolic BP elevation, mice were injected with an AT1R (Ang II [angiotensin II] type 1 receptor) antagonist (losartan), a muscarinic receptor antagonist (atropine), a β-adrenergic antagonist (propranolol), and a ganglionic blocker (chlorisondamine). Losartan did not blunt sPRR-induced elevation in systolic BP. Chlorisondamine treatment exacerbated the decrease in mean arterial pressure in male mice infused with sPRR. These results demonstrated that sPRR induced autonomic nervous dysfunction. Interestingly, plasma leptin levels were increased in high fat-fed C57BL/6 male mice infused with sPRR. Overall, our results indicated that sPRR increased systolic BP through an impairment of the baroreflex sensitivity and an increase in the sympathetic tone potentially mediated by leptin in high fat-fed C57BL/6 male mice.

Research progress in mechanism, diagnosis and treatment of neurogenic bowel dysfunction after spinal cord injury

Neurogenic bowel dysfunction (NBD) manifested as constipation and fecal incontinence often occurs after spinal cord injury (SCI). NBD affects patients' quality of life and is an urgent clinical problem to be solved. The mechanism of NBD is related to central and autonomic nervous system dysfunction, intestinal nervous system dysfunction, changes in intestinal microorganism composition and abnormal content of neurotransmitters. The evaluation method of NBD is mainly based on scoring and imaging, which lacks unified criteria, and the treatment method for NBD is the combination of traditional Chinese and Western medicine. The author summarizes the mechanism, evaluation method, treatment and nursing of NBD in order to provide new insight into these aspects to improve clinical efficacy. Key words: Spinal cord injuries; Neurogenic bowel; Quality of life

The characteristics of autonomic nerve dysfunction and sympathetic skin response in patients with gout

The characteristics of autonomic nerve dysfunction and sympathetic skin response in patients with gout

Association between laryngopharyngeal reflux disease and autonomic nerve dysfunction.

To assess autonomic nerve function in patients with laryngopharyngeal reflux disease (LPRD) and determine the correlation between LPRD and autonomic nerve dysfunction. Patients with suspected LPRD who visited our outpatient department were assessed using the reflux symptom index (RSI) and reflux finding score (RFS) scales. Eighty-one suspected LPRD patients with RSI > 13 and RFS > 7 were examined using 5-min short-range heart rate variability, and all were given proton pump inhibitor diagnostic treatment. The root mean square of successive R-R intervals, high-frequency (HF) power, standardized HF, and HF% were significantly lower in the case group than in the control group (p < 0.05); however, the low frequency (LF)/HF ratio was significantly higher in the case group (p < 0.05). There were no significant differences in the standard deviation of the average normal-to-normal interval, total power, LF power, and LF% between the two groups (p > 0.05). RSI, RFS, and disease duration were negatively correlated with HF power (r = - 0.89, -0.77, and -0.315, respectively; p < 0.05). The LF/HF ratio and disease duration were positively correlated (r = 0.315, p < 0.05). Autonomic nerve dysfunction was observed in our patients with LPRD. LPRD severity was significantly correlated with autonomic nerve dysfunction and negatively correlated with vagal nerve function.

Neural Microphysiological Systems for In Vitro Modeling of Peripheral Nervous System Disorders

PNS disease pathology is diverse and underappreciated. Peripheral neuropathy may result in sensory, motor or autonomic nerve dysfunction and can be induced by metabolic dysfunction, inflammatory dysfunction, cytotoxic pharmaceuticals, rare hereditary disorders or may be idiopathic. Current preclinical PNS disease research relies heavily on the use of rodent models. In vivo methods are effective but too time-consuming and expensive for high-throughput experimentation. Conventional in vitro methods can be performed with high throughput but lack the biological complexity necessary to directly model in vivo nerve structure and function. In this review, we survey in vitro PNS model systems and propose that 3D-bioengineered microphysiological nerve tissue can improve in vitro–in vivo extrapolation and expand the capabilities of in vitro PNS disease modeling.

Effects of chronic lead exposure on the sympathoexcitatory response associated with the P2X7 receptor in rat superior cervical ganglia.

Chronic lead exposure frequently brings about increased blood pressure and other cardiovascular diseases associated with autonomic nervous dysfunction. Purinergic signaling is involved in the development of abnormal sympathoexcitatory response due to myocardial ischemic injury. However, the potential implication of P2X7 receptor in altered sympathoexcitatory response caused by chronic lead exposure and the underlying mechanisms remain unclear. In this study, a rat model of chronic lead exposure was used to explore the changes in sympathoexcitatory response and possible involvement of P2X7 receptor in the superior cervical ganglion (SCG). Rats were divided into three groups called control, low lead and high lead groups according to daily lead exposure levels, i.e. 0, 0.5 and 2 g/L respectively. One year later, changes in P2X7 receptor expression in SCG, sympathetic nerve activity and myocardial function were measured for these rats. Our results showed that increased blood pressure and heart rate, decreased heart rate variability, enhanced cervical sympathetic nerve discharge, higher phosphorylation of ERK1/2, and up-regulated protein and mRNA levels of P2X7 expression in SCG occurred after lead exposure. In addition, double-label immunofluorescence staining of P2X7 receptor and glutamine synthetase (GS) revealed activation of the satellite glial cells of SCG by lead exposure. Moreover, knockdown of P2X7 could effectively relief the effect of lead exposure on enhanced expression of P2X7 receptor and GS. Thus our data suggest that the up-regulation of P2X7 receptor activity in satellite glial cells of SCG may contribute to the raised sympathoexcitatory response due to chronic lead exposure.

Royal Jelly Ameliorates Behavioral Deficits, Cholinergic System Deficiency, and Autonomic Nervous Dysfunction in Ovariectomized Cholesterol-Fed Rabbits.

Estrogen deficiency after menopause is associated with autonomic nervous changes, leading to memory impairment and increased susceptibility to Alzheimer’s disease (AD). Royal jelly (RJ) from honeybees (Apis mellifera) has estrogenic activity. Here, we investigated whether RJ can improve behavior, cholinergic and autonomic nervous function in ovariectomized (OVX) cholesterol-fed rabbits. OVX rabbits on high-cholesterol diet were administered with RJ for 12 weeks. The results showed that RJ could significantly improve the behavioral deficits of OVX cholesterol-fed rabbits and image structure of the brain. RJ reduced body weight, blood lipid, as well as the levels of amyloid-beta (Aβ), acetylcholinesterase (AchE), and malonaldehyde (MDA) in the brain. Moreover, RJ also increased the activities of choline acetyltransferase (ChAT) and superoxide dismutase (SOD) in the brain, and enhanced heart rate variability (HRV) and Baroreflex sensitivity (BRS) in OVX cholesterol-fed rabbits. Furthermore, RJ was also shown to reduce the content of Evans blue and the expression levels of Aβ, beta-site APP cleaving enzyme 1(BACE1), and receptor for advanced glycation end products (RAGE), and increase the expression level of LDL(low density lipoprotein) receptor-related protein 1 (LRP-1) in the brain. Our findings suggested that RJ has beneficial effects in neurological disorders of postmenopausal women, which were associated with reducing cholesterol and Aβ deposition, enhancing the estrogen levels and the activities of cholinergic and antioxidant systems, and ameliorating the blood–brain barrier (BBB) permeability and restoring autonomic nervous system.

Epicardial fat accumulation is an independent marker of impaired heart rate recovery in obese patients with obstructive sleep apnea.

Sympathetic nervous system activation plays a pivotal role in obese patients with obstructive sleep apnea (OSA), contributing to increased cardiovascular risk. Epicardial adipose tissue (EAT) activates cardiac autonomic nervous system. Our main study objective was to investigate effects of these autonomic dysfunction factors on post-exercise heart rate recovery (HRR). 36 patients, referred for clinical assessment of obesity (BMI > 30kg/m2), underwent overnight polysomnography, transthoracic echocardiography and cardiopulmonary exercise testing. Compared to non-OSA patients, OSA patients were older and displayed reduced body weight-indexed peak VO2. Cardiac output at peak exercise was similar among groups. Peak exercise arterio-venous oxygen content difference D[a-v]O2 was lower in OSA patients. In univariate linear analysis, age, AHI, EAT thickness, peak VO2 and diabetes were associated with blunted HRR. Multiple linear regression analysis showed that increased EAT thickness, AHI and diabetes were independently associated with lower HRR. For identical AHI value and diabetes status, HRR significantly decreased by 61.7% for every 1mm increase of EAT volume (p = 0.011). If HRR was treated as a categorical variable, EAT [odds ratio (OR) 1.78 (95% confidence interval [CI] 1.19-2.66); p = 0.005], and type 2 diabetes [OR 8.97 (95% CI 1.16-69.10); p = 0.035] were the only independent predictors of blunted HRR. Aerobic capacity and peak exercise D[a-v]O2 are impaired in obese OSA patients, suggesting abnormal peripheral oxygen extraction. EAT thickness is an independent marker of post-exercise HRR, which is a noninvasive marker of autonomic nerve dysfunction accompanying poor cardiovascular prognosis in obese patients.