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.

Species	Susceptibility genes (animal model)	Experimental approach	Effects on neurogenesis	Effects on behavior	References
C57BL6/Jmouse	DISC1	Knockdown of Disc1 via retroviral-mediated shRNA approach.	Enhanced dendritic outgrowth, soma hypertrophy, overextended migration, accelerated synapse formation of newborn granule neurons.	NS	[18]
C57BL6/Jmouse	DISC1	Knockdown of Disc1 via retroviral-mediated shRNA approach.	Mistargeted axonal mossy fibers and presynaptic differentiation of newborn granule neuron.	NS	[19]
C57BL6/Jmouse	DISC1	Knockdown of Disc1 via lentiviral-mediated shRNA approach.; Proliferation: BrdU (1 × 40 mg/kg, ip) at 2 hours pulsing chase.	Decreased cell proliferation	Hyperlocomotion in a novel environment.; Depressive-like behavior.	[20]
129/SvEv	DISC1; (Disc1^Tm1Kara 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 13	Decreased 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/Jmouse	SREB2; 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/Jmouse	Prenatal injection of synthetic double-stranded RNA polyriboinosinic polyribocytidylic acid (PolyI:C) into mice	BrdU (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]