A Transcription Factor Code Defines Nine Sensory Interneuron Subtypes in the Mechanosensory Area of the Spinal Cord

Alpinia oxyphylla is a traditional Chinese medicine widely used for treating diarrhea, ulceration, and enuresis. Moreover, A. oxyphylla is effective for cognitive function improvement and nerve regeneration. Multiple sclerosis (MS) is a chronic neuronal inflammatory autoimmune disease that commonly affects young adults in high-latitude regions. The aim of this study was to evaluate the beneficial effects of A. oxyphylla in an experimental autoimmune encephalomyelitis (EAE) mouse model, which is an extensively used model for human MS. The ethanolic extract of A. oxyphylla fruit (AO-1) was orally administered to EAE mice. Our results showed AO-1 significantly reduced EAE symptoms. Histopathological analysis showed AO-1 reduced demyelination, inflammation, gliosis, and axonal swelling in the spinal cord. Furthermore, immunohistochemistry and quantitative polymerase chain reaction (qPCR) studies revealed that the infiltration of CD4+, CD8+ T cells, and CD11b+ monocytes into the spinal cord decreased in the AO-1-treated group. Mechanistically, the Th1 transcription factor T-bet, Th17 transcription factor retinoic acid receptor–related orphan receptor γ (RORγt), and inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17 were reduced in the spinal cords of mice treated with AO-1. The expression levels of T-bet and RORγt were also lowered in the spleens of those mice. Further in vitro study showed AO-1 inhibited production of IFN-γ, IL-2, and tumor necrosis factor-α from MOG35-55-peptide-stimulated splenocytes. One component isolated from AO-1, yakuchinone A, inhibited IL-17 production in vitro and reduced EAE symptoms in the mice. Collectively, our results indicate that AO-1 ameliorated the severity of EAE in mice and may involve the regulation of Th1/Th17 response. A. oxyphylla warrants further investigation, particularly regarding its clinical benefits for MS.

Download Full-text

Transcription factor co-expression patterns indicate heterogeneity of oligodendroglial subpopulations in adult spinal cord

Glia ◽

10.1002/glia.20354 ◽

2006 ◽

Vol 54 (1) ◽

pp. 35-46 ◽

Cited By ~ 82

Author(s):

Masaaki Kitada ◽

David H. Rowitch

Keyword(s):

Spinal Cord ◽

Transcription Factor ◽

Expression Patterns ◽

Adult Spinal Cord

Download Full-text

Unc-4 acts to promote neuronal identity and development of the take-off circuit in the Drosophila CNS

10.1101/2019.12.24.887679 ◽

2019 ◽

Cited By ~ 1

Author(s):

Haluk Lacin ◽

W. Ryan Williamson ◽

Gwyneth M. Card ◽

James B. Skeath ◽

James W. Truman

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Transcription Factor ◽

Nerve Cord ◽

Ventral Nerve Cord ◽

Functional Organization ◽

Neuronal Circuits ◽

Sense Organs ◽

Neuronal Identity ◽

Cholinergic Neurotransmitter

ABSTRACTThe Drosophila ventral nerve cord (VNC), the fly equivalent of the spinal cord, is composed of thousands of neurons that are born from a set of individually identifiable stem cells. The VNC harbors neuronal circuits required for the execution of vital behaviors, such as flying and walking. Taking advantage of the lineage-based functional organization of the VNC and genetic tools we developed, we investigated the molecular and developmental basis of behavior by focusing on lineage-specific functions of the homeodomain transcription factor, Unc-4. We found that Unc-4 functions in lineage 11A to promote cholinergic neurotransmitter identity and suppress the GABA fate. In 7B lineage, Unc-4 promotes proper neuronal projections to the leg neuropil, the hub for leg-related neuronal circuits and a specific flight-related take-off behavior. We also uncovered that Unc-4 acts peripherally to promote the development of proprioceptive sense organs and the abilities of flies to execute specific leg-related behaviors such as walking, climbing, and grooming. Our findings, thus, initiates the work on revealing molecular and developmental events that shape the VNC related behaviors.

Download Full-text

Motoneurons regulate the central pattern generator during drug-induced locomotor-like activity in the neonatal mouse

eLife ◽

10.7554/elife.26622 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 29

Author(s):

Melanie Falgairolle ◽

Joshua G Puhl ◽

Avinash Pujala ◽

Wenfang Liu ◽

Michael J O’Donovan

Keyword(s):

Spinal Cord ◽

Transcription Factor ◽

Gap Junctions ◽

Central Pattern Generator ◽

Choline Acetyltransferase ◽

Pattern Generator ◽

Drug Induced ◽

Partial Blockade ◽

Lumbar Cord

Motoneurons are traditionally viewed as the output of the spinal cord that do not influence locomotor rhythmogenesis. We assessed the role of motoneuron firing during ongoing locomotor-like activity in neonatal mice expressing archaerhopsin-3 (Arch), halorhodopsin (eNpHR), or channelrhodopsin-2 (ChR2) in Choline acetyltransferase neurons (ChAT+) or Arch in LIM-homeodomain transcription factor Isl1+ neurons. Illumination of the lumbar cord in mice expressing eNpHR or Arch in ChAT+ or Isl1+ neurons, depressed motoneuron discharge, transiently decreased the frequency, and perturbed the phasing of the locomotor-like rhythm. When the light was turned off motoneuron firing and locomotor frequency both transiently increased. These effects were not due to cholinergic neurotransmission, persisted during partial blockade of gap junctions and were mediated, in part, by AMPAergic transmission. In spinal cords expressing ChR2, illumination increased motoneuron discharge and transiently accelerated the rhythm. We conclude that motoneurons provide feedback to the central pattern generator (CPG) during drug-induced locomotor-like activity.

Download Full-text