Copyright
©The Author(s) 2022.
World J Stem Cells. Mar 26, 2022; 14(3): 219-230
Published online Mar 26, 2022. doi: 10.4252/wjsc.v14.i3.219
Published online Mar 26, 2022. doi: 10.4252/wjsc.v14.i3.219
Genes or signaling pathways | Effects on adult neurogenesis | Behavior deviations | Ref. | Post-mortem or genetic studies |
DISC1 | Suppression of Disc1 expression results in accelerated neuronal integration, mispositioning of new DG granule cells, accelerated dendritic development, premature cell cycle exit and differentiation | Hyper-locomotion, depressive-like behavior, cognitive deficits (object place recognition test, Morris water maze test) | [16,18,20,23] | [130-132] |
NRG1 | NRG1 treatment induces increased ventral DG cell proliferation and neurogenesis.NRG1 regulates both excitatory and inhibitory synaptic transmission in the adult brain and abnormal neurotransmission and/or synaptic plasticity have been observed in the schizophrenic brain | Nrg1 hypomorphs showed hyperactivity in a number of tests, including the novel open-field test and the alternating-Y maze, impaired social behavior and increased aggression | [36,37,133] | [30-32] |
SNAP-25 | Snap-25 mutant mice display histologically and electrophysiologically immature DG neurons. Inactivation of Snap-25 in adult neural stem cells results in enhancement of proximal dendritic branching of new-born neurons in the DG and robust efferent mossy fiber output to the CA3 region | Working memory deficits, impaired contextual fear-discrimination learning | [47,48] | [43,44] |
CACNA1C | Cacna1c deletion results in decreased progenitor proliferation and reduced survival of new-born neurons | Cacna1c heterozygous mice display reduced locomotion, fear learning, and impaired spatial memory | [57-61] | [53-56] |
Reelin | Adult Reeler mutants show decreased proliferation, aberrant migration and dendritic development of new-born neurons | Heterozygous Reeler mice show a significant reduction in contextual fear conditioned learning and an age-dependent decrease in prepulse inhibition of startle | [82-84,86] | [69-71,74-77] |
Wnt signaling | Overexpression of stabilized β-catenin leads to enlarged brain and expanded neural precursor population. Wnt7a knockout mice show fewer neural stem cells. Wnt5a knockdown decreases the number of immature neurons. Tcf4 heterozygotes show reduced size of neural stem cell pool and impaired maturation and survival of adult-born neurons | Dvl knockout mice display reduced social interaction and deficits in prepulse inhibition of acoustic and tactile startle. Forebrain-specific β-catenin knockout mice show a depression-like phenotype. Apc heterozygote shows hypoactivity and a severe performance deficit in working memory | [90,96,106,107,134,135] | [98-100,112] |
Notch signaling | Inactivation of Notch1 blocks self-renewal of neural stem cells, reduces mitotic progenitors and neurogenesis. Adult deletion of RBPj leads to depletion and exhaustion of neural stem cells | Notch1 heterozygote displays deficits in spatial learning and memory | [100,121,122,128,129] | [116-118] |
- Citation: Hu L, Zhang L. Adult neural stem cells and schizophrenia. World J Stem Cells 2022; 14(3): 219-230
- URL: https://www.wjgnet.com/1948-0210/full/v14/i3/219.htm
- DOI: https://dx.doi.org/10.4252/wjsc.v14.i3.219