Neural Plasticity / 2012 / Article / Tab 2

Review Article

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

Table 2

Select animal studies investigating the effect of schizophrenia on adult hippocampal neurogenesis and behavior.

SpeciesSusceptibility genes (animal model)Experimental approachEffects on neurogenesisEffects on behaviorReferences

C57BL6/JmouseDISC1Knockdown of Disc1 via retroviral-mediated shRNA approach.Enhanced dendritic outgrowth, soma hypertrophy, overextended migration, accelerated synapse formation of newborn granule neurons.NS[18]

C57BL6/JmouseDISC1Knockdown of Disc1 via retroviral-mediated shRNA approach.Mistargeted axonal mossy fibers and presynaptic differentiation of newborn granule neuron.NS[19]

C57BL6/JmouseDISC1Knockdown of Disc1 via lentiviral-mediated shRNA approach.
Proliferation: BrdU (1 × 40 mg/kg, ip) at 2 hours pulsing chase.
Decreased cell proliferationHyperlocomotion in a novel environment.
Depressive-like behavior.
[20]

129/SvEvDISC1
(Disc1Tm1Kara mutant)
BrdU (50 mg/kg, ip) for 12 days.Decreased neural progenitors and immature neurons.
Misoriented apical dendrites on immature neurons.
Selective impairment in working memory[21]

129/SvEv
C57BL/6J
mouse
NPAS3
Npas3 null mouse
Proliferation: BrdU daily (50 mg/kg, ip) for 12 days and analysis on day 13Decreased cell proliferation in Npas3 null mouse.Locomotor hyperactivity, subtle gait defects, impairment of prepulse inhibition of acoustic startle, deficit in recognition memory, and altered anxiety-related responses.[22, 23]

C57BL6/JmouseSREB2
Overexpression of SREB2 transgenic mouse (Tg)
SREB2
null mouse
Proliferation: BrdU (3 × 100 mg/kg, ip) interval 2 hours apart and analysis on Day 3 after BrdU injection.
Survival: Three BrdU pulses (100 mg/kg, ip) at 2-hour intervals. Analysis on Day 30 following BrdU injection.
SREB2 Tg: decreased cell proliferation and neuronal maturation.
Dendritic morphology deficits in newborn granule neurons.
SREB2 null mouse: no change in cell proliferation, but increased neuronal survival rate.
SREB2 Tg: decreased discrimination in the spatial pattern separation.
SREB2 null mouse: enhanced discrimination in the spatial pattern separation.
[24]

C57BL6/JmousePrenatal injection of synthetic double-stranded RNA polyriboinosinic polyribocytidylic acid (PolyI:C) into miceBrdU (100 uL/20 g, ip) daily for 3 days and analysis
4weeks later.
Decreased neural progenitors.Behavioral deficits in the open field test and prepulse inhibition of the startle response.[25, 26]