Review Article

Functional Role of Adult Hippocampal Neurogenesis as a Therapeutic Strategy for Mental Disorders

Table 4

Select animal studies investigating the effect of electroconvulsive therapy (ECT) and deep brain stimulation (DBS) on adult hippocampal neurogenesis.

SpeciesECT treatmentExperimental approachEffects on neurogenesisMolecular targetReferences

Electroconvulsive therapy

Wistar ratSingle ECTBrdU (2 × 37.5 mg/kg, ip) at 12-hour intervals, starting at 0, 3, 5, 7, and 9 days after ECT and analysis 48 hours after the last injection of BrdU.Increased cell proliferation.NS[37]

Sprague-Dawley ratChronic ECT: once daily for 10 days
Proliferation: BrdU (4 × 45 mg/kg, ip) with 2-hour intervals, on 4 days after ECT and analysis at 24 hours after last BrdU injection.
Survival: BrdU (4 × 45 mg/kg, ip) with 2-hour intervals before ECT treatment and analysis at 28 days after last BrdU injection.
Increased cell proliferation and survival rate.NS[38]

Sprague-Dawley ratSingle ECT
Chronic ECT: once daily for 7 days
BrdU (150 mg/kg, ip) at 2 or 24 hours pulsing chase.2-hour BrdU pulse chase after single ECT: increased quiescent neural progenitors (QNPs) and slightly increased amplifying neural progenitors (ANPs) with no statistical significance.
At 24-hour BrdU pulse chase after single and chronic ECT: increased QNPs and ANPs.
VEGF[39]

Wistar ratECT every second day for a course of 8 seizuresStarting with seizure number 5, BrdU (1 × 50 mg/kg, ip) at 2-or 3-hour intervals following each ECT treatment. Injections were also given at the same time during the 3 days between treatments, resulting in a total of seven injections.Increased maturation of newborn neurons.NS[40]

Sprague-Dawley ratECT two timesNIT-GFP retroviral injection after ECT treatment.Increased mushroom spine density on newborn granule neuron dendrites.NS[41]

C57BL6/J
mouse
Single ECTBrdU (1 × 200 mg/kg, ip) at 2-hour pulsing chase.
GFP retroviral injection.
Increased cell proliferation.
Increased total dendritic length and dendritic complexity.
Gadd45b[42]

Bonnet monkeyECT: three times a week for four weeksProliferation: BrdU (100 mg/kg, iv) daily for 4 days.
Survival: BrdU (100 mg/kg, iv) daily for 4 days and analysis at 4 weeks after BrdU injection.
Increased cell proliferation and neuronal maturation.BCL2[43]

Deep Brain Stimulation

Sprague-Dawley ratAnterior thalamic nucleus was stimulated at 2.5 V, 90 μse of pulse width, and variable frequencies (10, 50, 130 Hz) for an hour.
BrdU (4 × 50 mg/kg, ip) with 3-hour interval and analysis at 24 hours or 4 weeks after last BrdU injection.
Increased cell proliferation.
No change in neuronal maturation
NS[44]

C57BL/6 mouse and nestin-CFPnuc transgenic mouseAnterior Thalamic Nucleus was stimulated at 2.5 V, 90 μs of pulse width, and frequencies 10 Hz (low) and 130 Hz (high) for an hour.
BrdU (3 × 50 mg/kg, ip) with 3-hour intervals and analysis at 24 hours or 30 days after last BrdU injection.Increased cell proliferation in high frequency but not low frequency.
Increased proliferation of amplifying neural progenitors (ANPs), but no change in quiescent neural progenitors (QNPs) at high frequency.
Increased neuronal maturation at high frequency but not low frequency.
NS[45]

Mixed genetic background between C57BL/6NTacfBr and 129Svev miceEntorhinal cortex at at 0–500 μA current, for 30–120 minutes, at 90 μs of pulse width and 130 Hz frequency.
Proliferation: BrdU (1 × 200 mg/kg, ip) injection on day 1, 3, 5, or 7 after stimulation and analysis at 24 hours after BrdU injection.
Neuronal maturation: IdU (57 mg/kg, ip) injections during the period of stimulation-induced increased proliferation (postoperative days 3–5), CldU (42.5 mg/kg, i.p.) injections during a similar period of baseline proliferation (postoperative days 7–9), and analysis about 10 weeks later.
Survival: BrdU daily (100 mg/kg, ip) with 8-hour intervals for 3 days on 1, 10, or 30 days before stimulation and postoperative analysis 3 weeks later.
Dendritic development: GFP-retroviral injection.
Increased cell proliferation after 60 or 120 minutes of stimulation and at 50, 250, and 500 μA.
No change in fate determination of newborn cells.
Increased dendritic length of newborn granule neurons but no change in nodes per neuron and dendritic spine size.
Improved spatial memory formation measured by water maze.[46]