scholarly journals Chronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sascha R. A. Alles ◽  
Max A. Odem ◽  
Van B. Lu ◽  
Ryan M. Cassidy ◽  
Peter A. Smith
Keyword(s):  
Dorsal Horn ◽  
Neuronal Excitability ◽  
Defined Medium ◽  
Regulatory Mechanisms ◽  
Superficial Dorsal Horn ◽  
Signal Identification ◽  
Organotypic Cultures ◽  
Serum Free ◽  
Neuronal Populations ◽  
Frequency Independent

AbstractBrain-derived neurotrophic factor (BDNF) is critically involved in the pathophysiology of chronic pain. However, the mechanisms of BDNF action on specific neuronal populations in the spinal superficial dorsal horn (SDH) requires further study. We used chronic BDNF treatment (200 ng/ml, 5–6 days) of defined-medium, serum-free spinal organotypic cultures to study intracellular calcium ([Ca2+]i) fluctuations. A detailed quantitative analysis of these fluctuations using the Frequency-independent biological signal identification (FIBSI) program revealed that BDNF simultaneously depressed activity in some SDH neurons while it unmasked a particular subpopulation of ‘silent’ neurons causing them to become spontaneously active. Blockade of gap junctions disinhibited a subpopulation of SDH neurons and reduced BDNF-induced synchrony in BDNF-treated cultures. BDNF reduced neuronal excitability assessed by measuring spontaneous excitatory postsynaptic currents. This was similar to the depressive effect of BDNF on the [Ca2+]i fluctuations. This study reveals novel regulatory mechanisms of SDH neuronal excitability in response to BDNF.

scholarly journals Chronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activity

2020 ◽  
Author(s):  
Sascha R.A. Alles ◽  
Max A. Odem ◽  
Van B. Lu ◽  
Ryan M. Cassidy ◽  
Peter A. Smith
Keyword(s):  
Dorsal Horn ◽  
Neuronal Excitability ◽  
Defined Medium ◽  
Regulatory Mechanisms ◽  
Superficial Dorsal Horn ◽  
Signal Identification ◽  
Organotypic Cultures ◽  
Serum Free ◽  
Neuronal Populations ◽  
Frequency Independent

AbstractBrain-derived neurotrophic factor (BDNF) is critically involved in the pathophysiology of chronic pain. However, the mechanisms of BDNF action on specific neuronal populations in the spinal superficial dorsal horn (SDH) requires further study. We used chronic BDNF treatment (200 ng/ml, 5-6 days) of defined-medium, serum-free spinal organotypic cultures to study intracellular calcium ([Ca2+]i) fluctuations. A detailed quantitative analysis of these fluctuations using the Frequency-independent biological signal identification (FIBSI) program revealed that BDNF simultaneously depressed activity in some SDH neurons while it unmasked a particular subpopulation of ‘silent’ neurons causing them to become spontaneously active. Blockade of gap junctions disinhibited a subpopulation of SDH neurons and reduced BDNF-induced synchrony in BDNF-treated cultures. BDNF reduced neuronal excitability by measuring spontaneous excitatory postsynaptic currents. This was similar to the depressive effect of BDNF on the [Ca2+]i fluctuations. This study reveals novel regulatory mechanisms of SDH neuronal excitability in response to BDNF.

ERK Integrates PKA and PKC Signaling in Superficial Dorsal Horn Neurons. I. Modulation of A-Type K+ Currents

2003 ◽  
Vol 90 (3) ◽  
pp. 1671-1679 ◽  
Author(s):  
Hui-Juan Hu ◽  
Kathi S. Glauner ◽  
Robert W. Gereau
Keyword(s):  
Protein Kinase ◽  
Dorsal Horn ◽  
Neuronal Excitability ◽  
Potassium Currents ◽  
Superficial Dorsal Horn ◽  
Dorsal Horn Neurons ◽  
Kinase C ◽  
Extracellular Signal ◽  
Whole Cell Recordings ◽  
K Currents

The transient outward potassium currents (also known as A-type currents or IA) are important determinants of neuronal excitability. In the brain, IA is modulated by protein kinase C (PKC), protein kinase A (PKA), and extracellular signal-related kinase (ERK), three kinases that have been shown to be critical modulators of nociception. We wanted to determine the effects of these kinases on IA in superficial dorsal horn neurons. Using whole cell recordings from cultured mouse spinal cord superficial dorsal horn neurons, we found that PKC and PKA both inhibit IA in these cells, and that PKC has a tonic inhibitory action on IA. Further, we provide evidence supporting the hypothesis that PKC and PKA do not modulate IA directly, but rather act as upstream activators of ERKs, which modulate IA. These results suggest that ERKs serve as signal integrators in modulation of IA in dorsal horn neurons and that modulation of A-type potassium currents may underlie aspects of central sensitization mediated by PKC, PKA, and ERKs.

Characterization of Superficial Dorsal Horn Neurons from “Tamamaki” Mice and Stability of their GAD67-EGFP Phenotype in Defined-Medium Organotypic Culture

Neuroscience ◽  
2018 ◽  
Vol 372 ◽  
pp. 126-140 ◽  
Author(s):  
Paul A. Boakye ◽  
Emma K.A. Schmidt ◽  
Vladimir Rancic ◽  
Bradley Kerr ◽  
Klaus Ballanyi ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Organotypic Culture ◽  
Defined Medium ◽  
Superficial Dorsal Horn ◽  
Dorsal Horn Neurons

Primary culture of rat ependymal cells in serum-free defined medium

1986 ◽  
Vol 390 (2) ◽  
pp. 199-209 ◽  
Author(s):  
M WEIBEL ◽  
B PETTMANN ◽  
J ARTAULT ◽  
M SENSENBRENNER ◽  
G LABOURDETTE
Keyword(s):  
Primary Culture ◽  
Defined Medium ◽  
Ependymal Cells ◽  
Serum Free

Dorsal Horn Pain Mechanisms

2019 ◽  
pp. 444-469 ◽  
Author(s):  
Hanns Ulrich Zeilhofer ◽  
Robert Ganley
Keyword(s):  
Dorsal Horn ◽  
Neuronal Excitability ◽  
Functional Organization ◽  
Synaptic Integration ◽  
Synaptic Efficacy ◽  
Pain Mechanisms ◽  
Pain Pathway ◽  
Pathological Pain ◽  
The Subject ◽  
Equivalent Structure

The spinal dorsal horn and its equivalent structure in the brainstem constitute the first sites of synaptic integration in the pain pathway. A huge body of literature exists on alterations in spinal nociceptive signal processing that contribute to the generation of exaggerated pain states and hence to what is generally known as “central sensitization.” Such mechanisms include changes in synaptic efficacy or neuronal excitability, which can be evoked by intense nociceptive stimulation or by inflammatory or neuropathic insults. Some of these changes cause alterations in the functional organization of dorsal horn sensory circuits, leading to abnormal pathological pain sensations. This article reviews the present state of this knowledge. It does not cover the contributions of astrocytes and microglia in detail as their functions are the subject of a separate chapter.

scholarly journals Brain Long Noncoding RNAs: Multitask Regulators of Neuronal Differentiation and Function

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3951
Author(s):  
Sarva Keihani ◽  
Verena Kluever ◽  
Eugenio F. Fornasiero
Keyword(s):  
Neuronal Differentiation ◽  
Neuronal Excitability ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Regulatory Mechanisms ◽  
Control Robustness ◽  
Living Organisms ◽  
And Function ◽  
Regulatory Functions ◽  
Neuronal Physiology

The extraordinary cellular diversity and the complex connections established within different cells types render the nervous system of vertebrates one of the most sophisticated tissues found in living organisms. Such complexity is ensured by numerous regulatory mechanisms that provide tight spatiotemporal control, robustness and reliability. While the unusual abundance of long noncoding RNAs (lncRNAs) in nervous tissues was traditionally puzzling, it is becoming clear that these molecules have genuine regulatory functions in the brain and they are essential for neuronal physiology. The canonical view of RNA as predominantly a ‘coding molecule’ has been largely surpassed, together with the conception that lncRNAs only represent ‘waste material’ produced by cells as a side effect of pervasive transcription. Here we review a growing body of evidence showing that lncRNAs play key roles in several regulatory mechanisms of neurons and other brain cells. In particular, neuronal lncRNAs are crucial for orchestrating neurogenesis, for tuning neuronal differentiation and for the exact calibration of neuronal excitability. Moreover, their diversity and the association to neurodegenerative diseases render them particularly interesting as putative biomarkers for brain disease. Overall, we foresee that in the future a more systematic scrutiny of lncRNA functions will be instrumental for an exhaustive understanding of neuronal pathophysiology.

scholarly journals Connectivity of pacemaker neurons in the neonatal rat superficial dorsal horn

2015 ◽  
Vol 523 (7) ◽  
pp. 1038-1053 ◽  
Author(s):  
Jie Li ◽  
Elizabeth Kritzer ◽  
Neil C. Ford ◽  
Shahriar Arbabi ◽  
Mark L. Baccei
Keyword(s):  
Dorsal Horn ◽  
Neonatal Rat ◽  
Superficial Dorsal Horn ◽  
Pacemaker Neurons

scholarly journals Subpopulation-specific patterns of intrinsic connectivity in mouse superficial dorsal horn as revealed by laser scanning photostimulation

2013 ◽  
Vol 591 (7) ◽  
pp. 1935-1949 ◽  
Author(s):  
Masafumi Kosugi ◽  
Go Kato ◽  
Stanislav Lukashov ◽  
Gautam Pendse ◽  
Zita Puskar ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Laser Scanning ◽  
Superficial Dorsal Horn ◽  
Intrinsic Connectivity ◽  
Laser Scanning Photostimulation

Continuous in vitro culture of Babesia divergens in a serum-free medium

Parasitology ◽  
1997 ◽  
Vol 115 (1) ◽  
pp. 81-89 ◽  
Author(s):  
N. GRANDE ◽  
E. PRECIGOUT ◽  
M. L. ANCELIN ◽  
K. MOUBRI ◽  
B. CARCY ◽  
...  
Keyword(s):  
Human Serum ◽  
Reduced Glutathione ◽  
Lipid Fraction ◽  
Basal Medium ◽  
Defined Medium ◽  
Specific Lipids ◽  
Serum Free ◽  
Babesia Divergens ◽  
Lipid Fractions

Babesia divergens was cultivated in RPMI 1640 (25 mM HEPES) supplemented with 10% human serum (RPMI-10% HS) with a high percentage of parasitized erythrocytes (PPE) ([ges ]40%). Standardization of in vitro tests, purification of exoantigens, biochemical studies and the safety of the culture handler motivated the development of a serum-free defined medium. Removal of serum greatly reduced the PPE but, after a period of adaptation, the culture was continuous and the parasite was able to develop a 3% routine PPE. Addition of vitamins or reduced glutathione in basal medium (RPMI) did not improve the PPE. The supplementation of basal medium with lipidic carrier (Albumax I or bovine serum albumin–Cohn's fraction V) promoted the growth of B. divergens with high PPE (>30%) close to those obtained in RPMI–10% HS. Neither protein nor lipid fractions alone were able to restore the growth of B. divergens. Nevertheless, the whole lipid fraction from serum or Albumax I added to delipidated albumin partially restored the growth (7% PPE), indicating that the presentation of specific lipids by a carrier is crucial for the parasite. All the data indicate that Albumax I can replace human serum offering the advantages of safety, standardization for chemosensitivity tests, and exoantigen purification.

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