scholarly journals Pathophysiological significance of increased α-synuclein deposition in sympathetic nerves in Parkinson disease: A post-mortem observational study

2021 ◽  
Author(s):  
Risa Isonaka ◽  
Patti Sullivan ◽  
David S Goldstein
Keyword(s):  
Parkinson Disease ◽  
Matched Control ◽  
Sympathetic Nerves ◽  
Left Ventricular ◽  
Myocardial Tissue ◽  
Post Mortem ◽  
Tissue Samples ◽  
Catecholaminergic Innervation ◽  
The Brain ◽  
Scalp Skin

Abstract Background: Parkinson disease (PD) is characterized by intra-neuronal deposition of the protein α-synuclein (α-syn) and by deficiencies of the catecholamines dopamine and norepinephrine (NE) in the brain and heart. Accumulation of α-syn in sympathetic noradrenergic nerves may provide a useful PD biomarker; however, whether α-syn buildup is pathophysiological has been unclear. If it were, one would expect associations of intra-neuronal α-syn deposition with catecholaminergic denervation and with decreased NE contents in the same samples. Methods: We assayed immunoreactive α-syn and tyrosine hydroxylase (TH, a marker of catecholaminergic innervation) concurrently with catecholamines in coded post-mortem scalp skin, submandibular gland (SMG), and apical left ventricular myocardial tissue samples from 14 patients with autopsy-proven PD and 12 age-matched control (CTRL) subjects who did not have a neurodegenerative disease. Results: PD patients had increased α-syn in sympathetic noradrenergically innervated arrector pili muscles (5.7 times CTRL, p<0.0001), SMG (35 times CTRL, p=0.0011), and myocardium (11 times CTRL, p=0.0011). Myocardial TH in the PD group was decreased from CTRL by 65% (p=0.0008), whereas the groups did not differ in TH in either arrector pili muscles or SMG. Similarly, myocardial NE was decreased by 92% in the PD group (p<0.0001), but the groups did not differ in NE in either scalp skin or SMG. Conclusions: PD entails increased α-syn in skin, SMG, and myocardial tissues. In skin and SMG augmented α-syn deposition in sympathetic nerves does not seem to be pathogenic. The pathophysiological significance of intra-neuronal α-syn deposition appears to be organ-selective and prominent in the heart.

Vorläufige Ergebnisse von 99mTc-HMPAO-SPECT-Untersuchungen bei endogenen Psychosen

1989 ◽  
Vol 28 (03) ◽  
pp. 88-91
Author(s):  
J. Schröder ◽  
H. Henningsen ◽  
H. Sauer ◽  
P. Georgi ◽  
K.-R. Wilhelm
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Regional Cerebral Blood Flow ◽  
Regions Of Interest ◽  
Post Mortem ◽  
Regional Cerebral Blood ◽  
Hmpao Spect ◽  
Endogenous Psychoses ◽  
The Brain ◽  
99Mtc Hmpao

18 psychopharmacologically treated patients (7 schizophrenics, 5 schizoaffectives, 6 depressives) were studied using 99mTc-HMPAO-SPECT of the brain. The regional cerebral blood flow was measured in three transversal sections (infra-/supraventricular, ventricular) within 6 regions of interest (ROI) respectively (one frontal, one parietal and one occipital in each hemisphere). Corresponding ROIs of the same section in each hemisphere were compared. In the schizophrenics there was a significantly reduced perfusion in the left frontal region of the infraventricular and ventricular section (p < 0.02) compared with the data of the depressives. The schizoaffectives took an intermediate place. Since the patients were treated with psychopharmaca, the result must be interpreted cautiously. However, our findings seem to be in accordance with post-mortem-, CT- and PET-studies presented in the literature. Our results suggest that 99mTc-HMPAO-SPECT may be helpful in finding cerebral abnormalities in endogenous psychoses.

scholarly journals Distribution of Melanin Pigmentation in 33 Organs of Thai Black-Bone Chickens (Gallus gallus domesticus)

Animals ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 777
Author(s):  
Korakot Nganvongpanit ◽  
Piyatida Kaewkumpai ◽  
Varankpicha Kochagul ◽  
Kidsadagon Pringproa ◽  
Veerasak Punyapornwithaya ◽  
...  
Keyword(s):  
Gallus Gallus ◽  
Gallus Domesticus ◽  
Melanin Pigment ◽  
Gallus Gallus Domesticus ◽  
Tissue Samples ◽  
Melanin Pigmentation ◽  
Chicken Breed ◽  
Brachial Vein ◽  
The Brain ◽  
Pigment Accumulation

The black-bone chicken (Gallus gallus domesticus) is a breed of chicken that is commonly found in Thailand. This breed is known for having a number of black colored organs. Consumers have been notably attracted to the black-bone chicken breed for the characteristic darkness that is observed in many of its organs. However, the degree of darkness in all organs of the black-bone chicken is still in question. Importantly, there have not yet been any published reports on the distribution of melanin pigment in the organs of the black-bone chicken. This research study aims to examine the distribution of the melanin pigment in 33 organs of the Thai black-bone chicken. Ten black-bone chickens (five male, five female) were included in this study. Thirty-two organs including the brain, spinal cord, sciatic nerve, larynx, trachea, syrinx, lungs, heart, pericardium, aorta, brachial vein, kidney, cloaca, oviduct, testis, gastrocnemius muscle, femur, tongue, esophagus, crop, proventriculus, gizzard, duodenum, jejunum, ileum, cecum, pancreas, liver, gall bladder, omentum, abdominal fat, spleen, and skin were examined in this study. Histological sections taken from tissue samples of each of these organs were studied. The findings revealed that the presence of the melanin pigment was not significantly different (p > 0.005) between male and female specimens. Notably, the liver was the only organ in which the melanin pigment had not accumulated. Consequently, there was not a uniform pattern of melanin pigment accumulation throughout the organs of the chickens. The melanin pigment was present in all of the tissue layers of most organs, while the melanin pigment was found in only specific layers of some of the organs. In conclusion, the distribution of melanin pigmentation in the organs of each of the animals in this study was found to be different. However, in some tissue samples, such as those obtained from the liver, no accumulation of the melanin pigment was observed.

Blood flow and high-energy phosphates in microregions of left ventricular subendocardium

1981 ◽  
Vol 240 (5) ◽  
pp. H804-H810 ◽  
Author(s):  
H. D. Kleinert ◽  
H. R. Weiss
Keyword(s):  
Blood Flow ◽  
Linear Relationship ◽  
Tissue Perfusion ◽  
High Energy ◽  
Left Ventricular ◽  
Significant Loss ◽  
Tissue Blood Flow ◽  
High Energy Phosphates ◽  
Tissue Samples ◽  
Heterogeneous Distribution

Blood flow and high-energy phosphate (HEP) content were determined simultaneously in multiple microregions of left ventricular subendocardium in 29 normal anesthetized open-chest rabbits by use of a new micromethod to determine whether a direct linear relationship existed between these parameters. Tissue samples weighed 1-2 mg. ATP and creatine phosphate (CP) content were quantitated in quick-frozen hearts by fluorometry at sites where tissue perfusion was measured by H2 clearance by use of bare-tipped platinum electrodes. A series of validation studies were conducted to ensure that 1) no significant damage to the tissue surrounding the electrode occurred during the period of experimentation and 2) no significant loss of biochemical constituents had occurred due to labile processes during freezing or storage of the tissue. Blood flow, ATP, and CP values averaged 79.1 +/- 24.1 (SD) ml.min-1.100 g-1, 4.9 +/- 1.3 mumol/g tissue, and 8.0 +/- 3.0 mumol/g tissue, respectively, and are similar to those reported in studies using larger tissue samples. Correlation between the heterogeneous distribution of tissue perfusion and HEP revealed no direct linear relationship between these parameters in the normal unstressed rabbit subendocardium.

scholarly journals Safety profile of the transcription factor EB (TFEB)-based gene therapy through intracranial injection in mice

2020 ◽  
Vol 11 (1) ◽  
pp. 241-250
Author(s):  
Zhenyu Li ◽  
Guangqian Ding ◽  
Yudi Wang ◽  
Zelong Zheng ◽  
Jianping Lv
Keyword(s):  
Gene Therapy ◽  
Transcription Factor ◽  
Neurodegenerative Diseases ◽  
Brain Tissue ◽  
Inflammatory Responses ◽  
Tissue Samples ◽  
Protein Levels ◽  
Virus Serotype ◽  
Transcription Factor Eb ◽  
The Brain

AbstractTranscription factor EB (TFEB)-based gene therapy is a promising therapeutic strategy in treating neurodegenerative diseases by promoting autophagy/lysosome-mediated degradation and clearance of misfolded proteins that contribute to the pathogenesis of these diseases. However, recent findings have shown that TFEB has proinflammatory properties, raising the safety concerns about its clinical application. To investigate whether TFEB induces significant inflammatory responses in the brain, male C57BL/6 mice were injected with phosphate-buffered saline (PBS), adeno-associated virus serotype 8 (AAV8) vectors overexpressing mouse TFEB (pAAV8-CMV-mTFEB), or AAV8 vectors expressing green fluorescent proteins (GFPs) in the barrel cortex. The brain tissue samples were collected at 2 months after injection. Western blotting and immunofluorescence staining showed that mTFEB protein levels were significantly increased in the brain tissue samples of mice injected with mTFEB-overexpressing vectors compared with those injected with PBS or GFP-overexpressing vectors. pAAV8-CMV-mTFEB injection resulted in significant elevations in the mRNA and protein levels of lysosomal biogenesis indicators in the brain tissue samples. No significant changes were observed in the expressions of GFAP, Iba1, and proinflammation mediators in the pAAV8-CMV-mTFEB-injected brain compared with those in the control groups. Collectively, our results suggest that AAV8 successfully mediates mTFEB overexpression in the mouse brain without inducing apparent local inflammation, supporting the safety of TFEB-based gene therapy in treating neurodegenerative diseases.

scholarly journals Aetiology-dependent impairment of mitochondrial function in the failing human heart

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Borger ◽  
D Scheiber ◽  
P Horn ◽  
D Pesta ◽  
U Boeken ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mitochondrial Function ◽  
Human Study ◽  
Left Ventricular ◽  
Myocardial Tissue ◽  
Funding Source ◽  
Ros Production ◽  
German Research Foundation ◽  
Long Term Outcome ◽  
Tissue Specimens

Abstract Background Alterations of mitochondrial function have been identified to play a role in Heart Failure (HF) pathophysiology. Oxidative phosphorylation (OXPHOS) capacity of the myocardium was shown to be reduced in the failing heart. Ineffective mitochondrial function promotes formation of reactive oxygen species (ROS) that may affect remodelling in ischemia. Thus far, human mitochondrial function comparing dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) resembling the main aetiologies of heart failure with reduced ejection fraction (HFrEF) has not been investigated. Purpose We hypothesised that 1. ROS production is elevated in left ventricular myocardial tissue specimens of ICM patients compared to DCM. 2. Mitochondrial OXPHOS capacity is higher in left ventricular myocardial tissue specimens of DCM compared to ICM patients. Methods Myocardial tissue was obtained from the left ventricular apex from 63 patients (38 ICM, 25 DCM) with advanced HFrEF requiring implantation of a Left Ventricular Assist Device (LVAD). We performed high-resolution respirometry (HRR, OROBOROS Oxygraph-2k) in saponine-permeabilised myocardial fibres and measured ROS production fluoroscopically via the Amplex Red method. Statistical analysis was conducted using GraphPad Prism 7 and IBM SPSS v26.0. Results Groups were of comparable age (61.5±1.2 vs. 59.3±2.4 years, p=n.s.), sex (87% vs 85% male, p=n.s.), diabetic status (32% vs 38.4% type 2 diabetes mellitus, p=n.s.), and body mass index (28.1±0.8 vs. 26.3±1.1 kg/m2, p=n.s.). We detected reduced myocardial mitochondrial OXPHOS capacity in ICM under state 3 conditions by about 15% (68.7±34.0 vs. 80.9±30.5 pmol/(s*mg), p&lt;0.05), after addition of Glutamate by 25% (78.9±38.7 vs. 104.8±41.2 pmol/(s*mg), p&lt;0.01) as well as after Succinate (115.5±65.5 vs. 155±62.0 pmol/(s*mg), p&lt;0.01), uncoupling agent FCCP (114.1±56.8 vs. 150.5±47.3 pmol/(s*mg), p&lt;0.01), and by about 40% after addition of Complex I inhibitor Rotenone (55.5±25.9 vs. 96.9±28.0 pmol/(s*mg), p&lt;0.001). We detected no difference in ROS production between ICM and DCM (0.6±0.05 vs. 0.76±0.08 pmol/(s*ml), p=n.s.). Conclusion This is the first human study deciphering distinct alterations in mitochondrial function (OXPHOS capacity) in ventricular myocardium of HFrEF patients. Future studies may address how distinct metabolic patterns at the time of implantation may relate to long-term outcome of HFrEF in terms of remodelling and recovery. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): DFG (German Research Foundation)

scholarly journals The impact of Wilson disease on myocardial tissue and function: a cardiovascular magnetic resonance study

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Janek Salatzki ◽  
Isabelle Mohr ◽  
Jannick Heins ◽  
Mert H. Cerci ◽  
Andreas Ochs ◽  
...  
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Myocardial Fibrosis ◽  
Wilson Disease ◽  
Left Ventricular ◽  
Myocardial Tissue ◽  
Cardiovascular Magnetic Resonance Study ◽  
Structural Remodeling ◽  
Cardiac Phenotype ◽  
The Impact

Abstract Background Systemic effects of altered serum copper processing in Wilson Disease (WD) might induce myocardial copper deposition and consequently myocardial dysfunction and structural remodeling. This study sought to investigate the prevalence, manifestation and predictors of myocardial tissue abnormalities in WD patients. Methods We prospectively enrolled WD patients and an age-matched group of healthy individuals. We applied cardiovascular magnetic resonance (CMR) to analyze myocardial function, strain, and tissue characteristics. A subgroup analysis of WD patients with predominant neurological (WD-neuro+) or hepatic manifestation only (WD-neuro−) was performed. Results Seventy-six patients (37 years (27–49), 47% women) with known WD and 76 age-matched healthy control subjects were studied. The prevalence of atrial fibrillation in WD patients was 5% and the prevalence of symptomatic heart failure was 2.6%. Compared to healthy controls, patients with WD had a reduced left ventricular global circumferential strain (LV-GCS), and also showed abnormalities consistent with global and regional myocardial fibrosis. WD-neuro+ patients presented with more severe structural remodeling and functional impairment when compared to WD-neuro− patients. Conclusions In a large cohort, WD was not linked to a distinct cardiac phenotype except CMR indexes of myocardial fibrosis. More research is warranted to assess the prognostic implications of these findings. Trial registration: This trial is registered at the local institutional ethics committee (S-188/2018).

scholarly journals Novel molecular transport medium used in combination with Xpert MTB/RIF ultra provides rapid detection of Mycobacterium bovis in African buffaloes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Charlene Clarke ◽  
Katrin Smith ◽  
Samantha J. Goldswain ◽  
Christopher Helm ◽  
David V. Cooper ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
Human Health Risk ◽  
Molecular Transport ◽  
Sampling Technique ◽  
High Specificity ◽  
Negative Control ◽  
Post Mortem ◽  
Tissue Samples ◽  
Transport Medium ◽  
Tissue Homogenates

AbstractMycobacterium bovis is the causative agent of bovine tuberculosis (bTB) in wildlife. Confirmation of M. bovis infection relies on mycobacterial culture, which is time-consuming. Collection and transportation of infectious material also pose a human health risk. PrimeStore Molecular Transport Medium (MTM) has been shown to effectively inactivate infectious organisms, making it a safe method for handling infectious samples. This study investigated an in-field sampling technique for rapid, safe detection of M. bovis in buffalo tissues. Potentially infected tissues from bTB test-positive buffaloes were swabbed at post-mortem examination and stored in PrimeStore MTM at ambient temperature until Xpert MTB/RIF Ultra testing was performed. Additionally, tissue samples were frozen and transported before homogenisation for culture and Ultra testing. Oral swabs were collected from M. bovis-unexposed buffaloes as a negative control cohort. Mycobacterium tuberculosis complex (MTBC) DNA was detected by Ultra in 13/16 tissue swabs and 9/16 matched tissue homogenates from culture-confirmed M. bovis-positive buffalo tissues. MTBC DNA was not detected in swabs from M. bovis-unexposed animals, showing the potentially high specificity of Ultra with PrimeStore swabs. PrimeStore MTM sample processing, in combination with the Ultra assay, has the potential to provide a safe, rapid post-mortem screening test for M. bovis in buffaloes.

β-blockade abolishes the augmented cardiac tPA release induced by transactivation of heterodimerised bradykinin receptor-2 and β2-adrenergic receptor in vivo

2014 ◽  
Vol 112 (11) ◽  
pp. 951-959 ◽  
Author(s):  
Morten Eriksen ◽  
Arnfinn Ilebekk ◽  
Alessandro Cataliotti ◽  
Cathrine Rein Carlson ◽  
Torstein Lyberg ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Sympathetic Nerves ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Adrenergic Stimulation ◽  
Β2 Adrenergic Receptor ◽  
Β Blocker

SummaryBradykinin (BK) receptor-2 (B2R) and β2-adrenergic receptor (β2AR) have been shown to form heterodimers in vitro. However, in vivo proofs of the functional effects of B2R-β2AR heterodimerisation are missing. Both BK and adrenergic stimulation are known inducers of tPA release. Our goal was to demonstrate the existence of B2R-β2AR heterodimerisation in myocardium and to define its functional effect on cardiac release of tPA in vivo. We further investigated the effects of a non-selective β-blocker on this receptor interplay. To investigate functional effects of B2R-β2AR heterodimerisation (i. e. BK transactivation of β2AR) in vivo, we induced serial electrical stimulation of cardiac sympathetic nerves (SS) in normal pigs that underwent concomitant BK infusion. Both SS and BK alone induced increases in cardiac tPA release. Importantly, despite B2R desensitisation, simultaneous BK infusion and SS (BK+SS) was characterised by 2.3 ± 0.3-fold enhanced tPA release compared to SS alone. When β-blockade (propranolol) was introduced prior to BK+SS, tPA release was inhibited. A persistent B2R-β2AR heterodimer was confirmed in BK-stimulated and nonstimulated left ventricular myocardium by immunoprecipitation studies and under non-reducing gel conditions. All together, these results strongly suggest BK transactivation of β2AR leading to enhanced β2AR-mediated release of tPA. Importantly, non-selective β-blockade inhibits both SS-induced release of tPA and the functional effects of B2R-β2AR heterodimerisation in vivo, which may have important clinical implications.

Role of sympathetic nerves during developing cardiac hypertrophy in Grollman hypertensive rats

1987 ◽  
Vol 253 (4) ◽  
pp. H818-H825
Author(s):  
R. J. Tomanek ◽  
D. W. Carlson ◽  
P. J. Palmer ◽  
R. K. Bhatnagar
Keyword(s):  
Cardiac Hypertrophy ◽  
Renovascular Hypertension ◽  
Volume Expansion ◽  
Peripheral Resistance ◽  
Sympathetic Nerves ◽  
Left Ventricular ◽  
Lv Function ◽  
Hypertensive Rats ◽  
Anterior Portion ◽  
Mitochondrial Volume

Peak left ventricular (LV) function, during rapid volume expansion, and cardiocyte structure were studied in rats with developing cardiac hypertrophy in response to Grollman hypertension (1 kidney, 1 figure 8) after chemical sympathectomy with 6-hydroxydopamine. This form of renovascular hypertension led to the same magnitude of hypertrophy in rats with or without sympathectomy. Indices of peak LV function, measured during acute volume expansion, tended to be normal or slightly higher in hypertensive rats than in controls. Sympathectomy in rats with hypertension significantly improved cardiac and stroke indices while decreasing total peripheral resistance at peak cardiac output. Despite similar magnitudes of LV hypertrophy (LVH) in the two hypertensive groups, cardiocytes in sympathectomized rats had higher mitochondrial volume densities and slightly lower myofibrillar volume densities. After regional sympathectomy of the anterior portion of the LV with phenol, mitochondrial volume density increased by 21% in hypertensive rats with LVH. These data indicate that, during the development of LVH in response to renovascular hypertension, sympathetic nerves do not contribute to the magnitude of LVH but may limit improvement in peak LV performance in response to increased preload. However, sympathetic nerves do play a role in the regulation of mitochondrial and myofibril growth.

Regulation of components of the brain and cardiac renin-angiotensin systems by 17β-estradiol after myocardial infarction in female rats

2006 ◽  
Vol 291 (1) ◽  
pp. R155-R162 ◽  
Author(s):  
Stephanie A. Dean ◽  
Junhui Tan ◽  
Roselyn White ◽  
Edward R. O’Brien ◽  
Frans H. H. Leenen
Keyword(s):  
Myocardial Infarction ◽  
Left Ventricular ◽  
Female Rats ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Brain Nuclei ◽  
Renin Angiotensin ◽  
Lv Dysfunction ◽  
17Β Estradiol ◽  
The Brain

The present study tested the hypothesis that 17β-estradiol (E2) inhibits increases in angiotensin-converting enzyme (ACE) and ANG II type 1 receptor (AT1R) in the brain and heart after myocardial infarction (MI) and, thereby, inhibits development of left ventricular (LV) dysfunction after MI. Age-matched female Wistar rats were treated as follows: 1) no surgery (ovary intact), 2) ovariectomy + subcutaneous vehicle treatment (OVX + Veh), or 3) OVX + subcutaneous administration of a high dose of E2 (OVX + high-E2). After 2 wk, rats were randomly assigned to coronary artery ligation (MI) and sham operation groups and studied after 3 wk. E2 status did not affect LV function in sham rats. At 2–3 wk after MI, impairment of LV function was similar across MI groups, as measured by echocardiography and direct LV catheterization. LV ACE mRNA abundance and activity were increased severalfold in all MI groups compared with respective sham animals and to similar levels across MI groups. In most brain nuclei, ACE and AT1R densities increased after MI. Unexpectedly, compared with the respective sham groups the relative increase was clearest (20–40%) in OVX + high-E2 MI rats, somewhat less (10–15%) in ovary-intact MI rats, and least (<10–15%) in OVX + Veh MI rats. However, because in the sham group brain ACE and AT1R densities increased in the OVX + Veh rats and decreased in the OVX + high-E2 rats compared with the ovary-intact rats, actual ACE and AT1R densities in most brain nuclei were modestly higher (<20%) in OVX + Veh MI rats than in the other two MI groups. Thus E2 does not inhibit upregulation of ACE in the LV after MI and amplifies the percent increases in ACE and AT1R densities in brain nuclei after MI, despite E2-induced downregulation in sham rats. Consistent with these minor variations in the tissue renin-angiotensin system, during the initial post-MI phase, E2 appears not to enhance or hinder the development of LV dysfunction.

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