Abstract P358: Cardiac Innervation Remodeling And Impaired Brain Derived Neurotrophic Factor (bdnf) Levels In Physiological Aging Vivo Model

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Andrea Elia ◽  
Alessandro Cannavo ◽  
Giuseppina Gambino ◽  
Maria Cimini ◽  
Nicola Ferrara ◽  
...  
Keyword(s):  
Nervous System ◽  
Nerve Fibers ◽  
Autonomic Nerve ◽  
Cardiac Innervation ◽  
Neuronal Function ◽  
Rat Serum ◽  
Physiological Aging ◽  
Protein Levels ◽  
Old Rats

Aging is a multifactorial process associated with gradual loss of function and decay involving several neurohormonal systems, such as the autonomic nervous system (ANS). Progressive remodeling of ANS, induces a circulating catecholamines spillover and cardiac autonomic fibers depletion with raising both morbidities and mortality risk. Neurotrophic factors (NF) play a pivotal role in modulating neuronal function and are impaired in cardiovascular disorders. Whether and how physiological aging impacts these neurobiomarkers and cardiac innervation remains still unclear. Therefore, we investigated the impact of aging on neurotrophins (such as BDNF and NGF) production and secretion and its consequences, on cardiac nervous system homeostasis. In vivo, we used young (age: 3 months; n=10) and old (age: 24 months; n=11) male Fisher rats. In vitro, human neuroblastoma cells (SH-SY5Y) were stimulated with serum withdrawn from both experimental groups. Old rats showed a significant reduction in overall ANS fiber density, sympathetic (marked by dopamine β-hydroxylase, dβh) and cholinergic compartment (evidenced by vesicular acetylcholine transporter, VaChT) compared to the young group, assessed by immunohistochemical staining. In addition, we observed a marked downregulation of GAP-43 and BDNF protein levels in left ventricle total lysates via immunoblot analysis, in aged hearts as opposed to young ones. Conversely, no changes were observed in NGF protein expression. To further investigate the autocrine effect of aging on autonomic nerve fibers, we treated SH-SY5Y cells in vitro, with blood serum obtained by young or old rats. Both stimuli induced a remarkable increase in neuronal sprouting, as evidenced via crystal violet assay. Nevertheless, we found a bulky drop in the neuronal function of cells stimulated with old rat serum. Interestingly, this effect was accompanied by a sizeable blunt in GAP-43 and BDNF protein levels, compared to cells treated with young rat serum. Taken together, our data suggest that neuronal function impairment aging-induced associated with significant BDNF impoverishment, might favor maladaptive remodeling of cardiac ANS.

Cellular Engineering: Molecular Repair of Membranes to Rescue Cells of the Damaged Nervous System

Neurosurgery ◽  
2001 ◽  
Vol 49 (2) ◽  
pp. 370-379 ◽  
Author(s):  
Richard B. Borgens
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
New Technology ◽  
Mechanical Damage ◽  
Nerve Impulse ◽  
Nerve Fibers ◽  
Acute Administration ◽  
Hydrophobic Core

Abstract PURPOSE The acute administration of hydrophilic polymers (polyethylene glycol) can immediately seal nerve membranes, preventing their continuing dissolution and secondary axotomy. Polymer application can even be used to reconnect, or fuse, the proximal and distal segments of severed axons in completely transected adult mammalian spinal cord. CONCEPT The sealing or fusion of damaged nerve membranes leads to a very rapid (minutes or hours) recovery of excitability in severely damaged nerve fibers, observed as a rapid return of nerve impulse conduction in vitro, as well as an in vivo recovery of spinal cord conduction and behavioral loss in spinal cord-injured adult guinea pigs. RATIONALE Surfactant application produces a rapid repair of membrane breaches through mechanisms of interaction between the polymers and the aqueous phase of damaged membranes, and their ability to insert into, or seal, the hydrophobic core of the axolemma exposed by mechanical damage. DISCUSSION This new technology applied to severe neurotrauma offers a clinically safe and practical means to rescue significant populations of spinal cord nerve fibers within 8 hours after damage—preventing their continued dissolution and secondary axotomy by secondary injury mechanisms. Application of this novel technology to other injuries to the peripheral and central nervous system is discussed, as well as a general application to soft tissue trauma.

scholarly journals Role of the Enteric Nervous System in the Elongated Sigmoid Colon of Patients With Sigmoid Volvulus

2014 ◽  
Vol 99 (6) ◽  
pp. 699-704
Author(s):  
Ryouichi Tomita ◽  
Kiminobu Sugitou ◽  
Kenichi Sakurai ◽  
Shigeru Fujisaki ◽  
Taro Ikeda ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Sigmoid Colon ◽  
Electrical Field Stimulation ◽  
Sigmoid Volvulus ◽  
Colon Resection ◽  
Autonomic Nerve ◽  
Cholinergic Nerves ◽  
Before And After

Abstract To clarify the physiologic function of the enteric nervous system (ENS) in the elongated sigmoid colon (ESC) of patients with sigmoid volvulus (SV), we examined the enteric nerve responses in lesional and normal longitudinal muscle strips (LMS) derived from patients with ESC and patients who underwent colon resection for colonic cancers. Thirty preparations of LMS were taken from the lesional sigmoid colons of 10 ESC patients with SV (8 men and 2 women, aged 53 to 80 years, mean 66.2 years). Forty preparations of LMS were taken from the normal sigmoid colons (NSC) of 20 patients with colonic cancer (12 men and 8 women, aged 55 to 76 years, mean 62.3 years). A mechanographic technique was used to evaluate in vitro muscle responses to electrical field stimulation (EFS) before and after treatment with various autonomic nerve blockers. Response to EFS before blockade of the adrenergic and cholinergic nerves was as follows: NSC and ESC significantly demonstrated relaxation reaction rather than contraction reaction (P = 0.0253, P < 0.0001, respectively). ESC showed relaxation reaction more than NSC (P = 0.1138). Response to EFS after blockade of the adrenergic and cholinergic nerves was as follows: NSC and ESC significantly demonstrated relaxation reaction via nonadrenergic noncholinergic (NANC) inhibitory nerves rather than contraction reaction via NANC excitatory nerves (P < 0.0001, P < 0.0001, respectively). ESC with SV significantly showed relaxation reaction more than NSC (P = 0.0092). An increased response of relaxation mediated NANC inhibitory nerves may play a role in impaired motility in the ESC of patients with SV.

scholarly journals Neuronal sensitivity to hyperoxia, hypercapnia, and inert gases at hyperbaric pressures

2003 ◽  
Vol 95 (3) ◽  
pp. 883-909 ◽  
Author(s):  
Jay B. Dean ◽  
Daniel K. Mulkey ◽  
Alfredo J. Garcia ◽  
Robert W. Putnam ◽  
Richard A. Henderson
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Ambient Pressure ◽  
Inert Gases ◽  
Neuronal Function ◽  
Cellular Mechanisms ◽  
Electrophysiological Studies ◽  
The Central Nervous System ◽  
Electrophysiological Methods

As ambient pressure increases, hydrostatic compression of the central nervous system, combined with increasing levels of inspired Po2, Pco2, and N2partial pressure, has deleterious effects on neuronal function, resulting in O2toxicity, CO2toxicity, N2narcosis, and high-pressure nervous syndrome. The cellular mechanisms responsible for each disorder have been difficult to study by using classic in vitro electrophysiological methods, due to the physical barrier imposed by the sealed pressure chamber and mechanical disturbances during tissue compression. Improved chamber designs and methods have made such experiments feasible in mammalian neurons, especially at ambient pressures <5 atmospheres absolute (ATA). Here we summarize these methods, the physiologically relevant test pressures, potential research applications, and results of previous research, focusing on the significance of electrophysiological studies at <5 ATA. Intracellular recordings and tissue Po2measurements in slices of rat brain demonstrate how to differentiate the neuronal effects of increased gas pressures from pressure per se. Examples also highlight the use of hyperoxia (≤3 ATA O2) as a model for studying the cellular mechanisms of oxidative stress in the mammalian central nervous system.

Species-specific action and distribution of tachykinin-related peptides in the foregut of the cockroaches Leucophaea maderae and Periplaneta americana.

1998 ◽  
Vol 201 (10) ◽  
pp. 1615-1626 ◽  
Author(s):  
D R Nässel ◽  
M Eckert ◽  
J E Muren ◽  
H Penzlin
Keyword(s):  
Nervous System ◽  
Periplaneta Americana ◽  
Large Cell ◽  
Nerve Fibers ◽  
Maximal Response ◽  
Dependent Manner ◽  
Stomatogastric Nervous System ◽  
Leucophaea Maderae ◽  
Species Specific

Nine tachykinin-related peptides (TRPs) have been isolated from the brain and intestine of the cockroach Leucophaea maderae. In the present investigation, two of the nine TRPs, LemTRP 1 and 5, were tested for their ability to stimulate contractions in the foregut of the cockroaches L. maderae and Periplaneta americana in vitro. The two LemTRPs and the related locust peptide locustatachykinin I (LomTK I) induced contractions in the foregut of P. americana in a dose-dependent manner, but had no myostimulatory action in L. maderae. A half-maximal response for the LemTRPs and LomTK I was obtained at 5x10(-9)mol l-1. In both species, the neuropeptide proctolin stimulated foregut contractions. Using an antiserum to LomTK I, we demonstrated that in both species there are LomTK-like-immunoreactive (LomTK-LI) cell bodies and fibers within the ganglia and nerves of the stomatogastric nervous system. However, correlated with the species-specific action of the TRPs, we found efferent LomTK-LI nerve fibers supplying muscle fibers in the foregut of P. americana, but not in L. maderae. In both cockroach species, there is a rich supply of proctolin-immunoreactive fibers to the foregut muscle. Some of the LomTK-LI fibers supplying the P. americana foregut muscle contain co-localized proctolin immunoreactivity. These fibers appear to be derived from a large cell body in the frontal ganglion which also displayed co-localized immunoreactivities. Since TRP-containing neurons are restricted to the nerves and ganglia of the stomatogastric nervous system both in P. americana and L. maderae, TRPs may be involved in the control of foregut movements in both species, but in P. americana the control may be more complex with the additional peripherally projecting LomTK-LI neurons.

scholarly journals PDK1 is a negative regulator of axon regeneration

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hyemin Kim ◽  
Jinyoung Lee ◽  
Yongcheol Cho
Keyword(s):  
Nervous System ◽  
Axon Regeneration ◽  
Dorsal Root Ganglion Neurons ◽  
Negative Regulator ◽  
Protein Levels ◽  
Adult Mice ◽  
The Central Nervous System ◽  
Ganglion Neurons

AbstractAxon regeneration in the central nervous system is inefficient. However, the neurons in the peripheral nervous system display robust regeneration after injury, indicating that axonal regeneration is differentially controlled under various conditions. To identify those molecules regulating axon regeneration, comparative analysis from dorsal root ganglion neurons at embryonic or adult stages is utilized, which reveals that PDK1 is functions as a negative regulator of axon regeneration. PDK1 is downregulated in embryonic neurons after axotomy. In contrast, sciatic nerve axotomy upregulated PDK1 at protein levels from adult mice. The knockdown of PDK1 or the chemical inhibition of PDK1 promotes axon regeneration in vitro and in vivo. Here we present PDK1 as a new player to negatively regulate axon regeneration and as a potential target in the development of therapeutic applications.

scholarly journals Peripheral nervous system involvement in systemic amyloidosis

2018 ◽  
Vol 10 (3) ◽  
pp. 12-18
Author(s):  
E. I. Safiulina ◽  
O. E. Zinovyeva ◽  
V. V. Rameev ◽  
L. V. Kozlovskaya-Lysenko
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Multiple Organ ◽  
Pathological Process ◽  
Nerve Fibers ◽  
Systemic Amyloidosis ◽  
Autonomic Nerve ◽  
Autonomic Nervous System Dysfunction ◽  
Sensorimotor Polyneuropathy ◽  
System Involvement

Peripheral nervous system involvement may be a main manifestation of systemic amyloidosis or occur in the later stages of the disease in the presence of multiple organ pathology. Focal, multiple mononeuropathy, radiculopathy, polyneuropathy, autonomic nervous system dysfunction, and myopathy develop depending on the localization of amyloid deposits in the peripheral nervous system. The most characteristic symptom in systemic amyloidosis is sensorimotor polyneuropathy accompanied in most cases by the involvement of autonomic nerve fibers in the pathological process. In cases of systemic amyloidosis, peripheral nervous system involvement is progressive, leading to disability, which makes the early diagnosis of the disease and its neurological manifestations and subsequent pathogenetic therapy relevant.

scholarly journals Effects of Manipulation of Noradrenergic Activities on the Expression of Dopaminergic Phenotypes in Aged Rat Brains

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110550
Author(s):  
Fei Zeng ◽  
Yan Fan ◽  
Russell W. Brown ◽  
Wesley Drew Gill ◽  
Jennifer B. Price ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Sensorimotor Gating ◽  
Rat Striatum ◽  
Protein Levels ◽  
Adrenoceptor Antagonist ◽  
Phosphorylated Akt ◽  
The Status ◽  
P300 Binding ◽  
Old Rats

This study investigated the effects of the pharmacological manipulation of noradrenergic activities on dopaminergic phenotypes in aged rats. Results showed that the administration of L-threo-3,4-dihydroxyphenylserine (L-DOPS) for 21 days significantly increased the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the striatum and substantia nigra (SN) of 23-month-old rats. Furthermore, this treatment significantly increased norepinephrine/DA concentrations in the striatum and caused a deficit of sensorimotor gating as measured by prepulse inhibition (PPI). Next, old rats were injected with the α2-adrenoceptor antagonist 2-methoxy idazoxan or β2-adrenoceptor agonist salmeterol for 21 days. Both drugs produced similar changes of TH and DAT in the striatum and SN. Moreover, treatments with L-DOPS, 2-methoxy idazoxan, or salmeterol significantly increased the protein levels of phosphorylated Akt in rat striatum and SN. However, although a combination of 2-methoxy idazoxan and salmeterol resulted in a deficit of PPI in these rats, the administration of 2-methoxy idazoxan alone showed an opposite behavioral change. The in vitro experiments revealed that treatments with norepinephrine markedly increased mRNAs and proteins of ATF2 and CBP/p300 and reduced mRNA and proteins of HDAC2 and HDAC5 in MN9D cells. A ChIP assay showed that norepinephrine significantly increased CBP/p300 binding or reduced HDAC2 and HDAC5 binding on the TH promoter. The present results indicate that facilitating noradrenergic activity in the brain can improve the functions of dopaminergic neurons in aged animals. While this improvement may have biochemically therapeutic indication for the status involving the degeneration of dopaminergic neurons, it may not definitely include behavioral improvements, as indicated by using 2-methoxy idazoxan only.

scholarly journals A three-dimensional in vitro model of the peripheral nervous system

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Sunghee Estelle Park ◽  
Jinchul Ahn ◽  
Hyo-Eun Jeong ◽  
Inchan Youn ◽  
Dongeun Huh ◽  
...  
Keyword(s):  
Cell Culture ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
In Vitro Model ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Nerve Fibers ◽  
Coculture Model ◽  
Vitro Model

AbstractRecent advances in three-dimensional (3D) cell culture models developed on organ-on-a-chip or microfluidic devices have shown their capability to recapitulate the in vivo microenvironment as well as their potential as tools in biomedical research. Here, we present an in vitro model of the peripheral nervous system (PNS) by establishing a coculture model of motor neurons (MNs) and Schwann cells (SCs) in a 3D environment in a microengineered extracellular matrix hydrogel scaffold. The collagen scaffold placed at the center of the microdevice provided a 3D cellular microenvironment where the axons of MNs were allowed to actively interact with SCs during their growth and maturation. By treating the MN–SC coculture model with ascorbic acid, we were able to model the myelination process in the PNS, which was evidenced by the increased expression of myelin markers in SCs. Moreover, we show that this can be reversed by treating myelinated nerve fibers with glial growth factor (neuregulin-1 isoform) to potentially block the formation of the myelin sheath and induce demyelination. Our 3D cell culture model may be used to achieve active control of the myelinating and demyelinating processes in the PNS and thus may offer new opportunities to study pathophysiological processes involved in motor neuron diseases by in vitro modeling.

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