Long-term modulation of tyrosine hydroxylase activity and expression by endothelin-1 and -3 in the rat anterior and posterior hypothalamus

2008 ◽  
Vol 294 (3) ◽  
pp. R905-R914 ◽  
Author(s):  
Guadalupe Perfume ◽  
Sabrina L. Nabhen ◽  
Karla Riquelme Barrera ◽  
María G. Otero ◽  
Liliana G. Bianciotti ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Cardiovascular Effects ◽  
Receptor Activation ◽  
Catecholaminergic Neurons ◽  
Endothelin System ◽  
Catecholaminergic Transmission ◽  
Underlying Mechanisms ◽  
G Protein Coupled ◽  
The Brain

Brain catecholamines are involved in the regulation of biological functions, including cardiovascular activity. The hypothalamus presents areas with high density of catecholaminergic neurons and the endothelin system. Two hypothalamic regions intimately related with the cardiovascular control are distinguished: the anterior (AHR) and posterior (PHR) hypothalamus, considered to be sympathoinhibitory and sympathoexcitatory regions, respectively. We previously reported that endothelins (ETs) are involved in the short-term tyrosine hydroxylase (TH) regulation in both the AHR and PHR. TH is crucial for catecholaminergic transmission and is tightly regulated by well-characterized mechanisms. In the present study, we sought to establish the effects and underlying mechanisms of ET-1 and ET-3 on TH long-term modulation. Results showed that in the AHR, ETs decreased TH activity through ETB receptor activation coupled to the nitric oxide, phosphoinositide, and CaMK-II pathways. They also reduced total TH level and TH phosphorylated forms (Ser 19 and 40). Conversely, in the PHR, ETs increased TH activity through a G protein-coupled receptor, likely an atypical ET receptor or the ETC receptor, which stimulated the phosphoinositide and adenylyl cyclase pathways, as well as CaMK-II. ETs also increased total TH level and the Ser 19, 31, and 40 phosphorylated sites of the enzyme. These findings support that ETs are involved in the long-term regulation of TH activity, leading to reduced sympathoinhibition in the AHR and increased sympathoexcitation in the PHR. Present and previous studies may partially explain the cardiovascular effects produced by ETs when applied to the brain.

scholarly journals Ventilation and neurochemical changes during µ-opioid receptor activation or blockade of excitatory receptors in the hypoglossal motor nucleus of goats

2017 ◽  
Vol 123 (6) ◽  
pp. 1532-1544 ◽  
Author(s):  
Thomas M. Langer ◽  
Suzanne E. Neumueller ◽  
Emma Crumley ◽  
Nicholas J. Burgraff ◽  
Sawan Talwar ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Pulmonary Ventilation ◽  
Respiratory Control ◽  
Nrem Sleep ◽  
Receptor Activation ◽  
Motor Nucleus ◽  
Physiological Conditions ◽  
Neurochemical Changes ◽  
Underlying Mechanisms ◽  
The Brain

Neuromodulator interdependence posits that changes in one or more neuromodulators are compensated by changes in other modulators to maintain stability in the respiratory control network. Herein, we studied compensatory neuromodulation in the hypoglossal motor nucleus (HMN) after chronic implantation of microtubules unilaterally ( n = 5) or bilaterally ( n = 5) into the HMN. After recovery, receptor agonists or antagonists in mock cerebrospinal fluid (mCSF) were dialyzed during the awake and non-rapid eye movement (NREM) sleep states. During day studies, dialysis of the µ-opioid inhibitory receptor agonist [d-Ala2, N-MePhe4, Gly-ol]enkephalin (DAMGO; 100 µM) decreased pulmonary ventilation (V̇i), breathing frequency ( f), and genioglossus (GG) muscle activity but did not alter neuromodulators measured in the effluent mCSF. However, neither unilateral dialysis of a broad spectrum muscarinic receptor antagonist (atropine; 50 mM) nor unilateral or bilateral dialysis of a mixture of excitatory receptor antagonists altered V̇i or GG activity, but all of these did increase HMN serotonin (5-HT) levels. Finally, during night studies, DAMGO and excitatory receptor antagonist decreased ventilatory variables during NREM sleep but not during wakefulness. These findings contrast with previous dialysis studies in the ventral respiratory column (VRC) where unilateral DAMGO or atropine dialysis had no effects on breathing and bilateral DAMGO or unilateral atropine increased V̇i and f and decreased GABA or increased 5-HT, respectively. Thus we conclude that the mechanisms of compensatory neuromodulation are less robust in the HMN than in the VRC under physiological conditions in adult goats, possibly because of site differences in the underlying mechanisms governing neuromodulator release and consequently neuronal activity, and/or responsiveness of receptors to compensatory neuromodulators. NEW & NOTEWORTHY Activation of inhibitory µ-opioid receptors in the hypoglossal motor nucleus decreased ventilation under physiological conditions and did not affect neurochemicals in effluent dialyzed mock cerebral spinal fluid. These findings contrast with studies in the ventral respiratory column where unilateral [d-Ala2, N-MePhe4, Gly-ol]enkephalin (DAMGO) had no effects on ventilation and bilateral DAMGO or unilateral atropine increased ventilation and decreased GABA or increased serotonin, respectively. Our data support the hypothesis that mechanisms that govern local compensatory neuromodulation within the brain stem are site specific under physiological conditions.

Peripheral and Central Catecholaminergic Neurons in Genetic and Experimental Hypertension in Rats

1976 ◽  
Vol 51 (s3) ◽  
pp. 377s-380s ◽  
Author(s):  
H. Grobecker ◽  
J. M. Saavedra ◽  
M. F. Roizen ◽  
V. Weise ◽  
I. J. Kopin ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Adrenal Glands ◽  
Experimental Hypertension ◽  
Hypertensive Rats ◽  
Hydroxylase Activity ◽  
Methyl Transferase ◽  
Spontaneously Hypertensive ◽  
Catecholaminergic Neurons ◽  
Wistar Kyoto ◽  
The Brain

1. Activity of peripheral and central catecholaminergic neurons was studied in spontaneously hypertensive rats (SHR) and deoxycorticosterone (DOCA)—salt hypertensive rats. 2. In young SHR (4 weeks) the plasma values of both noradrenaline and dopamine-β-hydroxylase activity were increased compared with those of normotensive rats of the Wistar/Kyoto strain. Total catecholamines (mostly adrenaline) were not significantly different. 3. In the adrenal glands of 2-weeks-old and 4-weeks-old SHR activities of tyrosine hydroxylase, dopamine-β-hydroxylase, phenylethanolamine-N-methyl transferase were decreased, compared to Wistar/Kyoto rats. 4. The adrenaline-forming enzyme was elevated in the A1 and A2 regions of the brain stem of 4-weeks-old SHR and in the A1 region of adult DOCA—salt hypertensive rats. 5. In the adrenal glands of adult DOCA—salt hypertensive rats tyrosine hydroxylase activity was increased. 6. These results implicate peripheral noradrenaline-containing neurons and central adrenaline-containing neurons in the development of genetic and experimental hypertension in rats.

scholarly journals Microglia: A Potential Therapeutic Target for Sepsis-Associated Encephalopathy and Sepsis-Associated Chronic Pain

2020 ◽  
Vol 11 ◽  
Author(s):  
Yi Li ◽  
Lu Yin ◽  
Zhongmin Fan ◽  
Binxiao Su ◽  
Yu Chen ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Neurological Dysfunction ◽  
Potential Therapeutic Target ◽  
The Central Nervous System ◽  
Underlying Mechanisms ◽  
The Relationship ◽  
The Brain

Neurological dysfunction, one of the severe manifestations of sepsis in patients, is closely related to increased mortality and long-term complications in intensive care units, including sepsis-associated encephalopathy (SAE) and chronic pain. The underlying mechanisms of these sepsis-induced neurological dysfunctions are elusive. However, it has been well established that microglia, the dominant resident immune cell in the central nervous system, play essential roles in the initiation and development of SAE and chronic pain. Microglia can be activated by inflammatory mediators, adjacent cells and neurotransmitters in the acute phase of sepsis and then induce neuronal dysfunction in the brain. With the spotlight focused on the relationship between microglia and sepsis, a deeper understanding of microglia in SAE and chronic pain can be achieved. More importantly, clarifying the mechanisms of sepsis-associated signaling pathways in microglia would shed new light on treatment strategies for SAE and chronic pain.

Cardiovascular Effects of Particulate Air Pollution

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Aruni Bhatnagar
Keyword(s):  
Fossil Fuels ◽  
Fine Particulate Matter ◽  
Cardiovascular Effects ◽  
Premature Mortality ◽  
Annual Review ◽  
Publication Date ◽  
Particulate Air Pollution ◽  
Underlying Mechanisms ◽  
Disease Exposure

Inhalation of fine particulate matter (PM2.5), produced by the combustion of fossil fuels, is an important risk factor for cardiovascular disease. Exposure to PM2.5 has been linked to increases in blood pressure, thrombosis, and insulin resistance. It also induces vascular injury and accelerates atherogenesis. Results from animal models corroborate epidemiological evidence and suggest that the cardiovascular effects of PM2.5 may be attributable, in part, to oxidative stress, inflammation, and the activation of the autonomic nervous system. Although the underlying mechanisms remain unclear, there is robust evidence that long-term exposure to PM2.5 is associated with premature mortality due to heart failure, stoke, and ischemic heart disease. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Adaptive and multifunctional hydrogel hybrid probes for long-term sensing and modulation of neural activity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Seongjun Park ◽  
Hyunwoo Yuk ◽  
Ruike Zhao ◽  
Yeong Shin Yim ◽  
Eyob W. Woldeghebriel ◽  
...  
Keyword(s):  
Foreign Body ◽  
Brain Regions ◽  
Foreign Body Response ◽  
Behavioral Studies ◽  
Hydrogel Matrix ◽  
Underlying Mechanisms ◽  
Hybrid Devices ◽  
The Brain ◽  
Body Response

AbstractTo understand the underlying mechanisms of progressive neurophysiological phenomena, neural interfaces should interact bi-directionally with brain circuits over extended periods of time. However, such interfaces remain limited by the foreign body response that stems from the chemo-mechanical mismatch between the probes and the neural tissues. To address this challenge, we developed a multifunctional sensing and actuation platform consisting of multimaterial fibers intimately integrated within a soft hydrogel matrix mimicking the brain tissue. These hybrid devices possess adaptive bending stiffness determined by the hydration states of the hydrogel matrix. This enables their direct insertion into the deep brain regions, while minimizing tissue damage associated with the brain micromotion after implantation. The hydrogel hybrid devices permit electrophysiological, optogenetic, and behavioral studies of neural circuits with minimal foreign body responses and tracking of stable isolated single neuron potentials in freely moving mice over 6 months following implantation.

scholarly journals Cerebral derailment after myocardial infarct: mechanisms and effects of the signaling from the ischemic heart to brain

2021 ◽  
Author(s):  
Paolo Gelosa ◽  
Laura Castiglioni ◽  
Joanna Rzemieniec ◽  
Majeda Muluhie ◽  
Marina Camera ◽  
...  
Keyword(s):  
Clinical Evidence ◽  
Heart Diseases ◽  
Myocardial Infarct ◽  
Cardiovascular Complications ◽  
Ischemic Heart ◽  
Underlying Mechanisms ◽  
Anxiety Depression ◽  
The Brain ◽  
A Current

AbstractMyocardial infarction (MI) is the leading cause of death among ischemic heart diseases and is associated with several long-term cardiovascular complications, such as angina, re-infarction, arrhythmias, and heart failure. However, MI is frequently accompanied by non-cardiovascular multiple comorbidities, including brain disorders such as stroke, anxiety, depression, and cognitive impairment. Accumulating experimental and clinical evidence suggests a causal relationship between MI and stroke, but the precise underlying mechanisms have not yet been elucidated. Indeed, the risk of stroke remains a current challenge in patients with MI, in spite of the improvement of medical treatment among this patient population has reduced the risk of stroke. In this review, the effects of the signaling from the ischemic heart to the brain, such as neuroinflammation, neuronal apoptosis, and neurogenesis, and the possible actors mediating these effects, such as systemic inflammation, immunoresponse, extracellular vesicles, and microRNAs, are discussed.

Alamandine but not angiotensin-(1-7) produces cardiovascular effects at the rostral insular cortex

2021 ◽  
Author(s):  
Fernanda Ribeiro Marins ◽  
Aline Cristina Oliveira ◽  
Fatimunnisa Qadri ◽  
Daisy Motta-Santos ◽  
Natalia Alenina ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Brain Region ◽  
Insular Cortex ◽  
Cardiovascular Effects ◽  
Endogenous Ligand ◽  
Renal Sympathetic Nerve Activity ◽  
G Protein Coupled ◽  
The Brain ◽  
Renal Sympathetic ◽  
Made In

Experiments aimed to evaluate the tissue distribution of Mas-related G-protein coupled receptor D (MrgD) revealed the presence of immunoreactivity for the MrgD protein in the rostral insular cortex (rIC), an important area for autonomic and cardiovascular control. In order to investigate the relevance of this finding, we evaluated the cardiovascular effects produced by the endogenous ligand of MrgD, alamandine, in this brain region. Mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded in urethane anesthetized rats. Unilateral microinjection of equimolar doses of alamandine (40pmol/100nl), angiotensin-(1-7), angiotensin II, angiotensin A and Mas/MrgD antagonist D-Pro7-Ang-1-7 (50pmol/100nl), Mas antagonist A779 (100pmol/100nl) or vehicle (0.9% NaCl) were made in different rats (N=4-6 per group) into rIC. To verify the specificity of the region, a microinjection of alamandine was also performed into intermediate insular cortex (iIC). Microinjection of alamandine in rIC produced an increase in MAP (Δ=15±2mmHg), HR (Δ=36±4bpm) and RSNA (Δ=31±4%), but was without effects at iIC. Strikingly, an equimolar dose of angiotensin-(1-7) at rIC did not produce any change in MAP, HR and RSNA. Angiotensin II and angiotensin A produced only minor effects. Alamandine effects were not altered by A-779, a Mas antagonist, but were completely blocked by the Mas/MrgD antagonist D-Pro7-Ang-(1-7). Therefore, we have identified a brain region in which alamandine/MrgD receptor but not angiotensin-(1-7)/Mas could be involved in the modulation of cardiovascular-related neuronal activity. This observation also suggests that alamandine might possess unique effects unrelated to angiotensin-(1-7) in the brain.

scholarly journals Underlying Mechanisms of Tinnitus: Review and Clinical Implications

2014 ◽  
Vol 25 (01) ◽  
pp. 005-022 ◽  
Author(s):  
James A. Henry ◽  
Larry E. Roberts ◽  
Donald M. Caspary ◽  
Sarah M. Theodoroff ◽  
Richard J. Salvi
Keyword(s):  
Health Care Professionals ◽  
Behavioral Interventions ◽  
Auditory Pathway ◽  
Common Denominator ◽  
Clear Understanding ◽  
Underlying Mechanisms ◽  
Normal Input ◽  
Central Auditory Pathway ◽  
The Brain

Background: The study of tinnitus mechanisms has increased tenfold in the last decade. The common denominator for all of these studies is the goal of elucidating the underlying neural mechanisms of tinnitus with the ultimate purpose of finding a cure. While these basic science findings may not be immediately applicable to the clinician who works directly with patients to assist them in managing their reactions to tinnitus, a clear understanding of these findings is needed to develop the most effective procedures for alleviating tinnitus. Purpose: The goal of this review is to provide audiologists and other health-care professionals with a basic understanding of the neurophysiological changes in the auditory system likely to be responsible for tinnitus. Results: It is increasingly clear that tinnitus is a pathology involving neuroplastic changes in central auditory structures that take place when the brain is deprived of its normal input by pathology in the cochlea. Cochlear pathology is not always expressed in the audiogram but may be detected by more sensitive measures. Neural changes can occur at the level of synapses between inner hair cells and the auditory nerve and within multiple levels of the central auditory pathway. Long-term maintenance of tinnitus is likely a function of a complex network of structures involving central auditory and nonauditory systems. Conclusions: Patients often have expectations that a treatment exists to cure their tinnitus. They should be made aware that research is increasing to discover such a cure and that their reactions to tinnitus can be mitigated through the use of evidence-based behavioral interventions.

scholarly journals How repair-or-dispose decisions under stress can initiate disease progression

2019 ◽  
Author(s):  
Andreas Nold ◽  
Danylo Batulin ◽  
Katharina Birkner ◽  
Stefan Bittner ◽  
Tatjana Tchumatchenko
Keyword(s):  
Tissue Damage ◽  
Decision Making Process ◽  
Biological Functions ◽  
Short Term ◽  
Damage Propagation ◽  
Underlying Mechanisms ◽  
The Brain ◽  
Insight Into ◽  
Conflicting Goals

AbstractGlia, the helper cells of the brain, are essential in maintaining neural resilience across time and varying challenges: By reacting to changes in neuronal health glia carefully balance repair or disposal of injured neurons to prevent further tissue damage. Malfunction of these interactions is implicated in many neurodegenerative diseases. Reductionist models with a minimal number of parameters provide the opportunity to gain insight into biological functions and inform experimental designs. We introduce such a model that mimics long-term implications of repair-or-dispose decisions. Depending on the functionality of the decision-making process, the model assumes four distinct tissue states: healthy, challenged, primed tissue at risk of acute damage propagation, and chronic neurodegeneration. These states of the model correspond to the progression stages observed in the most common neurodegenerative conditions. The underlying mechanisms are in agreement with experimental observations of glia-neuron crosstalk and reproduce a homeostatic balance between repairing and damage-inducing reactions. The model suggests that the onset of neurodegeneration results from a tug-of-war between two conflicting goals: short-term resilience to stressors vs long-term prevention of tissue damage.

scholarly journals The role of the brainstem in migraine: Potential brainstem effects of CGRP and CGRP receptor activation in animal models

Cephalalgia ◽  
2018 ◽  
Vol 39 (3) ◽  
pp. 390-402 ◽  
Author(s):  
Philip Robert Holland ◽  
Chonlawan Saengjaroentham ◽  
Marta Vila-Pueyo
Keyword(s):  
Regulatory Networks ◽  
Receptor Activation ◽  
Brain Disorder ◽  
Disability Adjusted Life ◽  
Unmet Demand ◽  
Hypothalamic Nuclei ◽  
Life Years ◽  
Underlying Mechanisms ◽  
The Brain

Background Migraine is a severe debilitating disorder of the brain that is ranked as the sixth most disabling disorder globally, with respect to disability adjusted life years, and there remains a significant unmet demand for an improved understanding of its underlying mechanisms. In conjunction with perturbed sensory processing, migraine sufferers often present with diverse neurological manifestations (premonitory symptoms) that highlight potential brainstem involvement. Thus, as the field moves away from the view of migraine as a consequence of purely vasodilation to a greater understanding of migraine as a complex brain disorder, it is critical to consider the underlying physiology and pharmacology of key neural networks likely involved. Discussion The current review will therefore focus on the available evidence for the brainstem as a key regulator of migraine biology and associated symptoms. We will further discuss the potential role of CGRP in the brainstem and its modulation for migraine therapy, given the emergence of targeted CGRP small molecule and monoclonal antibody therapies. Conclusion The brainstem forms a functional unit with several hypothalamic nuclei that are capable of modulating diverse functions including migraine-relevant trigeminal pain processing, appetite and arousal regulatory networks. As such, the brainstem has emerged as a key regulator of migraine and is appropriately considered as a potential therapeutic target. While currently available CGRP targeted therapies have limited blood brain barrier penetrability, the expression of CGRP and its receptors in several key brainstem nuclei and the demonstration of brainstem effects of CGRP modulation highlight the significant potential for the development of CNS penetrant molecules.

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