Review Article

Modulation of Adult Hippocampal Neurogenesis by Early-Life Environmental Challenges Triggering Immune Activation

Table 1

A summary of the studies investigating the effect of perinatal immune activation on postnatal hippocampal neurogenesis.

ReferenceAnimal modelInflammation-stimulating agentTime of exposureTime of neurogenesis assessmentEffect on proliferationEffect on survivalEffect on differentiationBehavioural correlatesEvidence of underlying cellular mechanism

Cui et al., (2009) [47]  Pregnant Sprague-Dawley ratsLPS 0.1 mg/kgGD 15/16PND 14Decrease No significant effectNo effect n/a n/a
LPS 0.05 mg/kgGD 18/19PND 14

PND 60 for both
n/a

No effect
Decrease in prolif/survival1
 No effect
No effect

No effect

Graciarena et al., (2010) [44]Pregnant Wistar ratsLPS 0.5 mg/kgGD 14–20 repeated injections every other dayPND 60Decrease No effectDecrease in the number of cells becoming young and mature neuronsImpaired recognition memory in novel object recognition taskMicroglial activation specific for DG; TGFβ 1 decrease in the DG

Graciarena et al., (2013) [49] Pregnant Wistar ratsLPS 0.5 mg/kgGD 14–20 repeated injections every other dayPND 60Decrease in cell proliferationNo effectDecrease in the number of cells becoming young and mature neurons n/aMicroglial activationand TGFβ 1 and Smad2/3 pathway involvement
Adult offspringLPS 1 mg/kgPND 60–68
injections every other day
PND 68Decrease No effect
Transient microglial activation, no change in TGFβ 1
PND 120 No effect

Järlestedt et al., (2013) [51] C57BL6 mice LPS 1 mg/kg PND 9 PND 41
Decrease n/a Decrease in the number of neurons and astrocytes n/a n/a
PND 60n/aDecrease in prolif/survival specific for dorsal hippocampus n/a

Jiang et al., (2012, 2013) [53, 54] Pregnant Sprague-Dawley ratsE. coli (endocervical injection) GD 15PND 3, 7, 14, 28Increase peaked at
PND 7
n/an/an/aIncrease in BDNF and TrkB protein levels in the hippocampus
PND 28No changeNo effectNo effectImpaired spatial learning in MWM taskNormalised BDNF and TrkB protein content

Lin and wang (2014) [50] Pregnant Sprague-Dawley ratsLPS 0.066 mg/kgGD 10.5PND 21

PND 90
Decrease

Decrease
No effect

No effect
Decrease in the number of young neurons
 Decrease in the number of young neurons



Increased expression of depressive-like behaviours
n/a

Meyer et al., (2006) [42]Pregnant C57BL6
mice
Poly I:C
5 mg/kg
GD 9PND 24n/an/aIncreased number of young neurons in subgranular and outer granular layerIncreased adulthood anxiety in OFIncreased reelin in hippocampus
GD 17PND 24 Increased number of young neurons in outer granular layer of DGPerseveration-like behaviourIncreased Caspase-3 in hippocampus

Prolif/survival: a parameter measured by the total number of BrdU+ cells few weeks after BrdU incorporation which combines effects of proliferation and survival. OF: open field; DG: dentate gyrus.