Electrical stimulation of the medullary pyramid promotes proliferation and differentiation of oligodendrocyte progenitor cells in the corticospinal tract of the adult rat

doi:10.1016/j.neulet.2010.05.043

Neuroscience Letters

Volume 479, Issue 2, 26 July 2010, Pages 128-133

https://doi.org/10.1016/j.neulet.2010.05.043 Get rights and content

Abstract

Endogenous tri-potential neural stem cells (eNSCs) exist in the adult spinal cord and differentiate primarily into oligodendrocytes (OLs) and astrocytes. Previous in vivo and in vitro studies have shown that during development proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) depend on activity in neighboring axons. However, this activity-dependent development of OPCs has not been examined in the adult CNS. In the present study, we stimulated unilateral corticospinal (CS) axons of the adult rat and investigated proliferation and differentiation of OPCs in dorsal corticospinal tract (dCST). eNSCs were labeled with the mitotic indicator 5-bromo-2′-deoxyuridine (BrdU). Phenotypes of proliferating cells were identified by double-immunolabeling of BrdU with a panel of antibodies to cell markers: NG2, Nkx2.2, APC, GFAP, and Glut-1. Electrical stimulation of CS axons increased BrdU labeled eNSCs and promoted the proliferation and differentiation of OPCs, but not astrocytes and endothelial cells. Our findings demonstrate the importance of neural activity in regulating OPC proliferation/differentiation in the mature CNS. Selective pathway electrical stimulation could be used to promote remyelination and recovery of function in CNS injury and disease.

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Acknowledgements

This work was supported by Hugo W. Moser Research Institute at Kennedy Krieger (JWM), NIH NS064004 (JHM) and NYS Spinal Injury Research Program grant C022064 (JHM).

References (27)

D. Becker et al.
Functional electrical stimulation helps replenish progenitor cells in the injured spinal cord of adult rats
Exp. Neurol.
(2010)
A.R. Calver et al.
Oligodendrocyte population dynamics and the role of PDGF in vivo
Neuron
(1998)
R.D. Fields et al.
ATP: an extracellular signaling molecule between neurons and glia
Trends Neurosci.
(2000)
R.D. Fields
Volume transmission in activity-dependent regulation of myelinating glia
Neurochem. Int.
(2004)
J.M. Gensert et al.
Endogenous progenitors remyelinate demyelinated axons in the adult CNS
Neuron
(1997)
B. Stevens et al.
Adenosine: a neuron-glial transmitter promoting myelination in the CNS in response to action potentials
Neuron
(2002)
P. Van Heyningen et al.
Control of progenitor cell number by mitogen supply and demand
Curr. Biol.
(2001)
B.A. Barres et al.
Proliferation of oligodendrocyte precursor cells dependents on electrical activity in axons
Nature
(1993)
M. Belci et al.
Magnetic brain stimulation can improve clinical outcome in incomplete spinal cord injured patients
Spinal Cord
(2004)
W. Bruce et al.
Remyelination in multiple sclerosis
J. Neurol. Sci.
(2003)

M. Brus-Ramer et al.

Electrical stimulation of spared corticospinal axons augments connections with ipsilateral spinal motor circuits after injury

J. Neurosci.

(2007)

D. Demerens et al.

Induction of myelination in the central nervous system by electrical activity

Proc. Natl. Acad. Sci.

(1996)

U. Engel et al.

Oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells derived from adult rat spinal cord: in vitro characteristics and response to PDGF, bFGF and NT-3

Glia

(1996)

Cited by (122)

Electrical stimulation promotes functional recovery after spinal cord injury by activating endogenous spinal cord-derived neural stem/progenitor cell: an in vitro and in vivo study
2024, Spine Journal
Electrical stimulation is a noninvasive treatment method that has gained popularity in the treatment of spinal cord injury (SCI). Activation of spinal cord-derived neural stem/progenitor cell (SC-NSPC) proliferation and differentiation in the injured spinal cord may elicit considerable neural regenerative effects.
This study aimed to explore the effect of electrical stimulation on the neurogenesis of SC-NSPCs.
This study analyzed the effects of electrical stimulation on neurogenesis in rodent SC-NSPCs in vitro and in vivo and evaluated functional recovery and neural circuitry improvements with electrical stimulation using a rodent SCI model.
Rats (20 rats/group) were assigned to sham (Group 1), SCI only (Group 2), SCI + electrode implant without stimulation (Group 3), and SCI + electrode with stimulation (Group 4) groups to count total SC-NSPCs and differentiated neurons and to evaluate morphological changes in differentiated neurons. Furthermore, the Basso, Beattie, and Bresnahan scores were analyzed, and the motor- and somatosensory-evoked potentials in all rats were monitored.
Biphasic electrical currents enhanced SC-NSPC proliferation differentiation and caused qualitative morphological changes in differentiated neurons in vitro. Electrical stimulation promoted SC-NSPC proliferation and neuronal differentiation and improved functional outcomes and neural circuitry in SCI models. Increased Wnt3, Wnt7, and β-catenin protein levels were also observed after electrical stimulation.
Our study proved the beneficial effects of electrical stimulation on SCI. The Wnt/β-catenin pathway activation may be associated with this relationship between electrical stimulation and neuronal regeneration after SCI.
The study confirmed the benefits of electrical stimulation on SCI based on cellular, functional, electrophysiological, and histological evidence. Based on these findings, we expect electrical stimulation to make a positive and significant difference in SCI treatment strategies.
Hebbian activity-dependent plasticity in white matter
2022, Cell Reports
Citation Excerpt :
This distinct plastic process has been confirmed to have two properties similar to synaptic plasticity: it is activity dependent, and it is implicated in learning. Its activity dependence has now been confirmed in animal models across a broad range of methods, including electrical stimulation (Li et al., 2010), optogenetics (Gibson et al., 2014), chemogenetics (Mitew et al., 2018), prevention of synaptic vesicle release by tetanus toxin (Mensch et al., 2015), and non-invasive transcranial magnetic stimulation (Cullen et al., 2021). Regarding its link to behavior, active myelination is critical for a wide range of learning behaviors (Kaller et al., 2017), including motor learning (McKenzie et al., 2014), fear learning (Pan et al., 2020), and spatial memory (Steadman et al., 2019).
Synaptic plasticity is required for learning and follows Hebb’s rule, the computational principle underpinning associative learning. In recent years, a complementary type of brain plasticity has been identified in myelinated axons, which make up the majority of brain’s white matter. Like synaptic plasticity, myelin plasticity is required for learning, but it is unclear whether it is Hebbian or whether it follows different rules. Here, we provide evidence that white matter plasticity operates following Hebb’s rule in humans. Across two experiments, we find that co-stimulating cortical areas to induce Hebbian plasticity leads to relative increases in cortical excitability and associated increases in a myelin marker within the stimulated fiber bundle. We conclude that Hebbian plasticity extends beyond synaptic changes and can be observed in human white matter fibers.
White Matter Changes Following Chronic Restraint Stress and Neuromodulation: A Diffusion Magnetic Resonance Imaging Study in Young Male Rats
2022, Biological Psychiatry Global Open Science
Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuromodulation technique, is an effective treatment for depression. However, few studies have used diffusion magnetic resonance imaging to investigate the longitudinal effects of rTMS on the abnormal brain white matter (WM) described in depression.
In this study, we acquired diffusion magnetic resonance imaging from young adult male Sprague Dawley rats to investigate 1) the longitudinal effects of 10- and 1-Hz low-intensity rTMS (LI-rTMS) in healthy animals; 2) the effect of chronic restraint stress (CRS), an animal model of depression; and 3) the effect of 10 Hz LI-rTMS in CRS animals. Diffusion magnetic resonance imaging data were analyzed using tract-based spatial statistics and fixel-based analysis.
Similar changes in diffusion and kurtosis fractional anisotropy were induced by 10- and 1-Hz stimulation in healthy animals, although changes induced by 10-Hz stimulation were detected earlier than those following 1-Hz stimulation. Additionally, 10-Hz stimulation increased axial and mean kurtosis within the external capsule, suggesting that the two protocols may act via different underlying mechanisms. Brain maturation–related changes in WM, such as increased corpus callosum, fimbria, and external and internal capsule fiber cross-section, were compromised in CRS animals compared with healthy control animals and were rescued by 10-Hz LI-rTMS. Immunohistochemistry revealed increased myelination within the corpus callosum in LI-rTMS–treated CRS animals compared with those that received sham or no stimulation.
Overall, decreased WM connectivity and integrity in the CRS model corroborate findings in patients experiencing depression with high anxiety, and the observed LI-rTMS–induced effects on WM structure suggest that LI-rTMS might rescue abnormal WM by increasing myelination.
Translational perspective: Neuroregenerative strategies and therapeutics for traumatic spinal cord injury
2022, Neural Repair and Regeneration after Spinal Cord Injury and Spine Trauma
The last three decades have witnessed transformative advances in biology and neuroscience. Still, regeneration of axons after traumatic spinal cord injury (SCI) remains a significant medical challenge and need. The central nervous system has a limited capacity for endogenous repair as compared to other tissues such as nerve, bone, skin, and liver. Key knowledge areas contributing to the multidisciplinary field of neuroregeneration therapeutics include molecular and developmental neurobiology, stem cell and peripheral nerve biology, experimental neuropathology, neurophysiology, and biomedical and materials engineering. Key experimental techniques include cell culture, microfluidics, high-throughput screening, animal modeling, and human clinical trials. This chapter reviews key concepts with a particular view of the field's evolution, what has been tested in people with SCI, and what therapeutic applications seem feasible in the near future to accomplish more effective regeneration. We briefly describe some unifying key molecular pathways as currently understood, such as PTEN inhibition of the PI3K–Akt–mTOR pathway, and while we emphasize specific interactions such as reducing axonal growth inhibition, few of the molecules discussed have only one activity. The reader is referred to online resources such as the Kegg Pathway database (https://www.genome.jp/kegg/pathway.html) for greater detail and omics integrated systems analyses focused on SCI.
Visual deprivation induces transient upregulation of oligodendrocyte progenitor cells in the subcortical white matter of mouse visual cortex
2021, IBRO Neuroscience Reports
Sensory experience influences proliferation and differentiation of oligodendrocyte progenitor cells (OPCs). Enhanced sensorimotor experience promoted the lineage progression of OPCs and myelination in the gray matter and white matter (WM) of sensorimotor cortex. In the visual cortex, reduced experience reportedly delayed the maturation of myelination in the gray matter, but whether and how such experience alters the subcortical WM is unclear. Here we investigated if binocular enucleation from the onset of eye opening (i.e., P15) affects the cell state of OPCs in mouse primary visual cortex (V1). Proliferative cells in the WM declined nearly half over 3 days from postnatal day (P) 25. A 3-day BrdU-labeling showed gradual decline in proliferation rates from P19 to P28. Binocular enucleation resulted in an increase in the cycling state of the OPCs that were proliferated from P22 to P25 but not before or after this period. This increase in proliferative OPCs was not associated with lineage progression toward differentiated oligodendrocytes. Proliferative OPCs arose mostly due to symmetric cell division but also asymmetric formation of proliferative and quiescent OPCs. By P30, almost all the proliferated cells exited the cell cycle. Maturing oligodendrocytes among the proliferated cells increased at this age, but most of them disappeared over 25 days. The cell density of the maturing oligodendrocytes was unaffected by binocular enucleation, however. These data suggest that binocular enucleation transiently elevates proliferative OPCs in the subcortical WM of V1 during a specific period of the fourth postnatal week without subsequently affecting the number of maturing oligodendrocytes several days later.
Life-long oligodendrocyte development and plasticity
2021, Seminars in Cell and Developmental Biology
Oligodendrocyte precursor cells (OPCs) originate in localized germinal zones in the embryonic neural tube, then migrate and proliferate to populate the entire central nervous system, both white and gray matter. They divide and generate myelinating oligodendrocytes (OLs) throughout postnatal and adult life. OPCs express NG2 and platelet-derived growth factor receptor alpha subunit (PDGFRα), two functionally important cell surface proteins, which are also widely used as markers for OPCs. The proliferation of OPCs, their terminal differentiation into OLs, survival of new OLs, and myelin synthesis are orchestrated by signals in the local microenvironment. We discuss advances in our mechanistic understanding of paracrine effects, including those mediated through PDGFRα and neuronal activity-dependent signals such as those mediated through AMPA receptors in OL survival and myelination. Finally, we review recent studies supporting the role of new OL production and “adaptive myelination” in specific behaviours and cognitive processes contributing to learning and long-term memory formation. Our article is not intended to be comprehensive but reflects the authors’ past and present interests.

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Neuroscience Letters

Abstract

Section snippets

Acknowledgements

References (27)

Functional electrical stimulation helps replenish progenitor cells in the injured spinal cord of adult rats

Exp. Neurol.

Oligodendrocyte population dynamics and the role of PDGF in vivo

Neuron

ATP: an extracellular signaling molecule between neurons and glia

Trends Neurosci.

Volume transmission in activity-dependent regulation of myelinating glia

Neurochem. Int.

Endogenous progenitors remyelinate demyelinated axons in the adult CNS

Neuron

Adenosine: a neuron-glial transmitter promoting myelination in the CNS in response to action potentials

Neuron

Control of progenitor cell number by mitogen supply and demand

Curr. Biol.

Proliferation of oligodendrocyte precursor cells dependents on electrical activity in axons

Nature

Magnetic brain stimulation can improve clinical outcome in incomplete spinal cord injured patients

Spinal Cord

Remyelination in multiple sclerosis

J. Neurol. Sci.

Electrical stimulation of spared corticospinal axons augments connections with ipsilateral spinal motor circuits after injury

J. Neurosci.

Induction of myelination in the central nervous system by electrical activity

Proc. Natl. Acad. Sci.

Oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells derived from adult rat spinal cord: in vitro characteristics and response to PDGF, bFGF and NT-3

Glia

Cited by (122)

Electrical stimulation promotes functional recovery after spinal cord injury by activating endogenous spinal cord-derived neural stem/progenitor cell: an in vitro and in vivo study

Hebbian activity-dependent plasticity in white matter

White Matter Changes Following Chronic Restraint Stress and Neuromodulation: A Diffusion Magnetic Resonance Imaging Study in Young Male Rats

Translational perspective: Neuroregenerative strategies and therapeutics for traumatic spinal cord injury

Visual deprivation induces transient upregulation of oligodendrocyte progenitor cells in the subcortical white matter of mouse visual cortex

Life-long oligodendrocyte development and plasticity