Table 3.
Responses of Cells of the CNS to DCEF
| Cell types | Cell lines or primary cell | Electric field (V/m) | Length of exposure (h) | Main published observations/ novel observations |
References |
|---|---|---|---|---|---|
| Neurons | Derived from dorsal root ganglia of chick embryos | 15–140 | 3.7–6.3 | • Neurites grow faster towards the cathode. | (Jaffe and Poo, 1979) |
| Neurons | Derived from neural tube of Xenopus laevis embryos | 4–190 | 16–20 | • 7V/m is identified as the minimal DCEF to induce a change in direction of neurites (towards the cathode). • More neurons grow neurites in 6–8V/m DCEF. |
(Hinkle et al., 1981) |
| Neurons | Derived from neural tube of Xenopus laevis embryos | 100–1000 | 6 | • Neurite growth towards the cathode is accelerated, and decelerated towards the anode. • Those perpendicular to the field change direction towards the cathode. • Neurite sprouting is increased towards the cathode. • The total number of neurons with neurites, as well as neurite length, are increased. These effects are abolished by concanavalin A. |
(Patel and Poo, 1982) |
| Neurons | Derived from neural tube of Xenopus laevis embryos | 50–155 | 3 | • Reabsorption/retraction of neurites facing the anode. • Fewer filipodia on neurites facing the anode and more on neurites facing the cathode. |
(McCaig, 1987) |
| Neurons | NlE-115 mouse neuroblastoma cells | 100–1000 | 1 | • Increase in sprouting, change of direction and growth rate in neurites facing the cathode. • Increase of reabsorption of neurites facing the anode. • Increase in extracellular calcium in the cell compartment facing the cathode. |
(Bedlack et al., 1992) |
| Neurons | PC12 cells | 5–100 | 48 | • Increase in the total of number neurites oriented towards the anode. | (Cork et al., 1994) |
| Neurons | Derived from spinal neurons of Xenopus laevis embryos | 50–200 | 4 | • Branching and direction change in neurites towards the cathode are blocked by aminoglycosides (inositol phospholipid inhibitor). • Combined exposure to neomycin (polyphosphoinositide metabolism inhibitor) and extracellular Ca2+ reverses these effects. • Neurite growth rate is modified by aminoglycosides and external Ca2+. |
(Erskine et al., 1995) |
| Neurons | Derived from neural tube of Xenopus laevis embryos | 50–200 | 5 | • Increased changes in direction, branching and growth rate towards the cathode are modulated by voltage-gated calcium channels and intracellular calcium storage. | (Stewart et al., 1995) |
| Neurons | Derived from neural tube of Xenopus laevis embryos | 100 | 12 | • Change in direction of neurites towards the cathode is independent of intracellular and extracellular Ca2+. | (Palmer et al., 2000) |
| Neurons | Derived from neural tube of Xenopus laevis embryos | 50–200 | 5 | • Neurotrophins promote growth cone guidance and neurite sprouting towards the cathode but decrease neurite growth towards the anode. | (McCaig et al., 2000) |
| Neurons | Derived from spinal neurons of Xenopus laevis embryos | 150 | 5 | • Dynamics of microfilaments and microtubules is essential for the migration of neurites towards the cathode. | (Rajnicek et al., 2006b) |
| Neurons | Derived from spinal neurons of Xenopus laevis embryos | 150 | 5 | • Rho, Rac and Cdc42 (of the Rho family of GTPases) are necessary for the initial neurite change in direction towards the cathode. • Following 2h of stimulation, Rho and Cdc42 are still important but Rac signaling dominates. • PI-3K, MAPK and ERK1/2 are not needed for redirection towards the cathode. |
(Rajnicek et al., 2006a) |
| Neurons | Derived from dorsal root ganglia of chick embryos | 24–44 | 0.167–1.167 | • Neurite length is greater 24h after DCEF stimulation. • This is not influenced by the type of media, the surface coating nor growth supplements. |
(Wood and Willits, 2009) |
| Neurons | Rat dorsal root ganglion | 10–100 | 8 | • Neurite outgrowth is enhanced by DCEF. • This outgrowth is greater in co-cultures of neurons and Schwann cells. |
(Koppes et al., 2011) |
| Neurons | N2a cells | 25–100 | 24 | • No differences in cell viability between stimulation intensities. • Cell bodies orient parallel to the DCEF and elongate when stimulated at 25 and 50V/m. • Neurites are elongated and reoriented towards the cathode. • GAP-43 protein is increased at 25 and 50V/m. |
Present observations |
| Neurons | Dopaminergic explants | 50 | 24 | • Neurites orient and are longer towards the cathode. | Present observations |
| Astrocytes | Rat primary cortical asctrocytes | 50–500 | 7–15.5 | • Cell protrusions reorient perpendicularly the DCEF following an initial retraction of the neurites followed by an extension. | (Borgens et al., 1994) |
| Astrocytes | Rat primary cortical asctrocytes | 50–1500 | 0.5 | • Reduced glycolysis rate at 50V/m, unchanged at 100V/m and increased at >150V/m. | (Huang et al., 1997) |
| Astrocytes | Rat primary cortical asctrocytes | 500 | 24 | • Cells align perpendicularly to the electric field. | (Alexander et al., 2006) |
| Astrocytes | C8-D1A cells | 25–100 | 24 | • Cells bodies and protrusions are elongated. • Cells bodies and protrusions align perpendicularly to the electric field. |
Present observations |
| Microglia | Quiescent BV-2 cells | 25–100 | 24 | • The number of cells with protrusions is increased at 25 and 50V/m. • Cell protrusion length is increased at 25V/m and 50V/m. • Cell bodies and protrusions reorient perpendicular to the electric field. • COX-2 expression is increased at 100V/m. |
Present observations |
| Microglia | Activated BV-2 cells | 25–100 | 24 | • The number of viable cells and cells with protrusions is reduced by the electric field. • Shrinking of cell bodies and protrusions. |
Present observations |
Abbreviations: Cdc42, cell division control protein 42 homolog; COX-2, cyclooxygenase-2; DCEF, direct current electric field; ERK1/2, extracellular-signal-regulated kinase; GAP-43, growth-associated protein-43; GTP, guanosine triphosphate; PI-3K, phosphoinositide 3-kinase; MAPK, mitogen-activated protein kinase; Rac, ras-related C3 botulinum toxin substrate.