Elsevier

Biological Psychiatry

Volume 62, Issue 5, 1 September 2007, Pages 505-512
Biological Psychiatry

Original Article
Electroconvulsive Seizures Stimulate Glial Proliferation and Reduce Expression of Sprouty2 within the Prefrontal Cortex of Rats

https://doi.org/10.1016/j.biopsych.2006.11.014Get rights and content

Background

Reductions in cell number are found within the medial prefrontal cortex (PFC) in major depression and bipolar disorder, conditions for which electroconvulsive therapy (ECT) is a highly effective treatment. We investigated whether electroconvulsive seizure (ECS) in rats stimulates cellular proliferation in the PFC immediately and four weeks after the treatments. In parallel, we examined if ECS also alters the expression of Sprouty2 (SPRY2), an inhibitor of cell proliferation.

Methods

Sprague-Dawley rats received 10 days of ECS treatments and bromodeoxyuridine (BrdU) injections. After a four week survival period, we estimated the density and number of BrdU-, proliferating cell nuclear antigen (PCNA)-, and SPRY2-immunoreactive cells in the medial (infralimbic) PFC (ILPFC). We also determined the percentage of BrdU-labeled cells that were immunoreactive for markers specific to oligodendrocytes, astrocytes, endothelial cells and neurons.

Results

ECS dramatically enhanced the proliferation of new cells in the infralimbic PFC, and this effect persisted four weeks following the treatments. The percentage of new cells expressing oligodendrocyte precursor cell markers increased slightly following ECS. In contrast, ECS dramatically reduced the number of cells expressing SPRY2.

Conclusions

ECS stimulates long-lasting increases in glial proliferation within the ILPFC. ECS also decreases SPRY2 expression in the same region, an effect that might contribute to increased glial proliferation.

Section snippets

Rats, ECS and BrdU Procedures

A total of 10 Male Sprague–Dawley rats (Charles River Labs, Wilmington, Massachusetts) weighing 150–200 g at the beginning of the study were used, and they were housed in groups of 3-4 under standard conditions with free access to food and water. Experiments were conducted in accordance with the 1996 Guide for the Care and Use of Laboratory Animals (National Institute of Health), as well as McLean Hospital policies.

ECS-treated rats (n = 5) were administered seizures once daily for 10 days in

Results

When ILPFC volume and all cell counts were analyzed together, there was a significant overall effect of ECS treatment (F(1,10) = 4.769, p < .05). There were no significant differences between hemispheres (F(1,10) = .217, ns), so data from both hemispheres were averaged and the mean values were used in subsequent analyses.

Discussion

ECS stimulates cellular proliferation in the medial prefrontal cortex, a region with impaired cellular plasticity in mood disorders. We observed a three-fold increase in the number of new (i.e., BrdU-immunoreactive) cells produced at the time of ECS as well as proliferating (PCNA-labeled) cells four weeks following the end of ECS. We also found that a higher percentage of newly born cells express NG2, a marker for oligodendrocyte precursor cells (Levine et al. 2001); there was a trend towards

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      Such tDCS-induced metaplastic changes (increased neuronal excitability after anodal stimulation) had been noted before in human and animal studies (Liebetanz et al., 2002) while the major involvement of glia was a novel find. Some of the effects of ECT, tDCS and TMS may be due to an increase in glial number, since at least ECT has been shown to induce proliferation of glial cells expressing NG2 or oligodendrocyte markers in rat PFC (Madsen et al., 2005; Ongur et al., 2007), and NG2 or OX-42 microglial markers in amygdala (Wennstrom et al., 2004) and hippocampus (Wennstrom et al., 2003). However, cellular proliferation does not necessarily guarantee long-term survival of the new cells, which also depends on environmental factors.

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