scholarly journals Innervated adrenomedullary microphysiological system to model prenatal nicotine and opioid exposure

2020 ◽  
Author(s):  
Jonathan R. Soucy ◽  
Gabriel Burchett ◽  
Ryan Brady ◽  
David T. Breault ◽  
Abigail N. Koppes ◽  
...  
Keyword(s):  
Sympathetic Neurons ◽  
Critical Role ◽  
Catecholamine Release ◽  
Control Mechanisms ◽  
Adrenal Chromaffin Cell ◽  
Pinning Effect ◽  
Organ Systems ◽  
Functional Immaturity ◽  
Prenatal Nicotine ◽  
Adrenal Chromaffin

The transition to extrauterine life results in a critical surge of catecholamines necessary for increased cardiovascular, respiratory, and metabolic activity. The mechanisms mediating adrenomedullary catecholamine release are poorly understood, given the sympathetic adrenomedullary control systems’ functional immaturity. Important mechanistic insight is provided by newborns delivered by cesarean section or subjected to prenatal nicotine or opioid exposure, demonstrating the impaired release of adrenomedullary catecholamines. To investigate mechanisms regulating adrenomedullary innervation, we developed compartmentalized 3D microphysiological systems (MPS) by exploiting the meniscus pinning effect via GelPins, capillary pressure barriers between cell-laden hydrogels. The MPS comprises discrete 3D cultures of adrenal chromaffin cells and preganglionic sympathetic neurons within a contiguous bioengineered microtissue. Using this model, we demonstrate that adrenal chromaffin innervation plays a critical role in hypoxia-medicated catecholamine release. Furthermore, opioids and nicotine were shown to affect adrenal chromaffin cell response to a reduced oxygen environment, but neurogenic control mechanisms remained intact. GelPin containing MPS represent an inexpensive and highly adaptable approach to study innervated organ systems and improve drug screening platforms by providing innervated microenvironments.

The Main Sequence of Human Optokinetic Afternystagmus (OKAN)

2009 ◽  
Vol 101 (6) ◽  
pp. 2889-2897 ◽  
Author(s):  
Andre Kaminiarz ◽  
Kerstin Königs ◽  
Frank Bremmer
Keyword(s):  
Neural Networks ◽  
Eye Movements ◽  
Main Sequence ◽  
Critical Role ◽  
Saccade Target ◽  
Control Mechanisms ◽  
Visually Guided ◽  
Background Characteristics ◽  
Optokinetic Afternystagmus

Different types of fast eye movements, including saccades and fast phases of optokinetic nystagmus (OKN) and optokinetic afternystagmus (OKAN), are coded by only partially overlapping neural networks. This is a likely cause for the differences that have been reported for the dynamic parameters of fast eye movements. The dependence of two of these parameters—peak velocity and duration—on saccadic amplitude has been termed “main sequence.” The main sequence of OKAN fast phases has not yet been analyzed. These eye movements are unique in that they are generated by purely subcortical control mechanisms and that they occur in complete darkness. In this study, we recorded fast phases of OKAN and OKN as well as visually guided and spontaneous saccades under identical background conditions because background characteristics have been reported to influence the main sequence of saccades. Our data clearly show that fast phases of OKAN and OKN differ with respect to their main sequence. OKAN fast phases were characterized by their lower peak velocities and longer durations compared with those of OKN fast phases. Furthermore we found that the main sequence of spontaneous saccades depends heavily on background characteristics, with saccades in darkness being slower and lasting longer. On the contrary, the main sequence of visually guided saccades depended on background characteristics only very slightly. This implies that the existence of a visual saccade target largely cancels out the effect of background luminance. Our data underline the critical role of environmental conditions (light vs. darkness), behavioral tasks (e.g., spontaneous vs. visually guided), and the underlying neural networks for the exact spatiotemporal characteristics of fast eye movements.

Propofol-induced Inhibition of Catecholamine Release Is Reversed by Maintaining Calcium Influx

2016 ◽  
Vol 124 (4) ◽  
pp. 878-884 ◽  
Author(s):  
Liping Han ◽  
Stephen Fuqua ◽  
Quanlin Li ◽  
Liyu Zhu ◽  
Xiaoyan Hao ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Calcium Influx ◽  
Sympathetic Neurons ◽  
Reduce Blood Pressure ◽  
Catecholamine Release ◽  
Unexpected Finding ◽  
Norepinephrine Release ◽  
Triggered Release ◽  
Induced Hypotension ◽  
High K

Abstract Background Propofol (2,6-diisopropylphenol) is one of the most frequently used anesthetic agents. One of the main side effects of propofol is to reduce blood pressure, which is thought to occur by inhibiting the release of catecholamines from sympathetic neurons. Here, the authors hypothesized that propofol-induced hypotension is not simply the result of suppression of the release mechanisms for catecholamines. Methods The authors simultaneously compared the effects of propofol on the release of norepinephrine triggered by high K+-induced depolarization, as well as ionomycin, by using neuroendocrine PC12 cells and synaptosomes. Ionomycin, a Ca2+ ionophore, directly induces Ca2+ influx, thus bypassing the effect of ion channel modulation by propofol. Results Propofol decreased depolarization (high K+)-triggered norepinephrine release, whereas it increased ionomycin-triggered release from both PC12 cells and synaptosomes. The propofol (30 μM)-induced increase in norepinephrine release triggered by ionomycin was dependent on both the presence and the concentration of extracellular Ca2+ (0.3 to 10 mM; n = 6). The enhancement of norepinephrine release by propofol was observed in all tested concentrations of ionomycin (0.1 to 5 μM; n = 6). Conclusions Propofol at clinically relevant concentrations promotes the catecholamine release as long as Ca2+ influx is supported. This unexpected finding will allow for a better understanding in preventing propofol-induced hypotension.

scholarly journals Effects of Cultured Adrenal Chromaffin Cell Implants on Hindlimb Reflexes of the6-OHDA Lesioned Rat

1994 ◽  
Vol 5 (2) ◽  
pp. 89-102 ◽  
Author(s):  
Bruce E. Pulford ◽  
Andrea R. Mihajlov ◽  
Howard O. Nornes ◽  
L. Ray Whalen
Keyword(s):  
Spinal Cord ◽  
Glyoxylic Acid ◽  
Reflex Activity ◽  
Emg Activity ◽  
Lumbar Region ◽  
Adrenal Chromaffin Cell ◽  
Electrophysiological Testing ◽  
Withdrawal Reflexes ◽  
6 Hydroxydopamine ◽  
Adrenal Chromaffin

The effects of implantation of cultured adrenal medullary cells on the recovery of neurotransmitter specific reflex activity were studied in the rat spinal cord using electrophysiological testing methods. Cell suspensions of cultured neonatal adrenal medullary chromaffin (AM) cells (which produce catecholamines), or Schwann (Sc) cells (controls) were implanted into the lumbar region of the spinal cord 2 weeks after catecholamine (CA) denervation by intracisternal injection of 6-hydroxydopamine (6-OHDA). All cells were taken from 7 day neonates and cultured for 10 days in the presence of nerve growth factor (NGF). Three months after implantation, the extent of implant-associated recovery of reflex activity was determined by measuring electromyogram (EMG) activity and force associated with the long latency component of the hindlimb withdrawal reflex (which is CA modulated). After the electrophysiological testing, rats were anesthetized, and the spinal cords were rapidly removed and frozen. Spinal cords were sectioned longitudinally, and implanted cells were visualized using glyoxylic acid techniques. Labelled sections were examined to determine cell survival. Results indicate that 1) chromaffin cells survive for 3 months in the segments of the cord into which they have been implanted and 2) rats implanted with AM cells have significantly more forceful withdrawal reflexes than those that received Sc cells or received no implant after lesioning.

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