TABLE 5.
Comparison of Histologic, Neuromorphologic, Neurocognitive, and Behavioral Outcomes Between Animal Models of Maternal Immune Activation (MIA), DISC1, and Neuregulin-1
| MIA Modela | DISC1b | Neuregulin-1c |
|---|---|---|
| Histologic abnormalities | ||
|
| ||
| Smaller, denser neurons in hippocampus; pyknotic cells in hippocampus | Reduced hippocampal gray matter volume and altered engagement of the hippocampus during several cognitive tasks in schizophrenia patients and healthy subjects with mutant DISC1 (72) | Hippocampal hypofunction and loss of interneurons (73) |
| Densely packed pyramidal cells; pyramidal cell atrophy | Defects in axonal targeting to CA3 pyramidal cells and development of synaptic outputs (74) | Decreased spine density on hippocampal pyramidal neurons (73) |
| Abnormal neuronal migration to layers II/III in cortex (unpublished, described in reference 56) | DISC1 suppression via RNAi resulted in abnormal neuronal migration to layers II/III in cerebral cortex (70) | Impaired thalamocortical migration (75) |
| Reduced NMDA receptor subunit 1 (NR1) expression in the hippocampus | No studies | Perfusion of neuregulin increased internalized NMDA receptor expression in cultured prefrontal cortex cells (76) |
| Reduced parvalbumin+ neurons in prefrontal cortex | Reduced parvalbumin+ neurons in medial prefrontal cortex. Parvalbumin+ cells displaced in dorsolateral frontal cortex (77) | Neuregulin receptor ErbB4 preferentially expressed by majority of parvalbumin+ interneurons in cerebral cortex (78) |
| Layer- and region-specific changes in the expression of SNAP-25 | Decrease in SNAP-25 (71) | No studies |
| Delay in hippocampal myelination | Compromised DISC1 function in zebrafish disrupts oligodendrocyte development and results in myelination defects (69) | Hypomyelination (79) |
|
| ||
| Neuromorphologic abnormalities | ||
|
| ||
| Ventricular enlargement | Mild ventricular enlargement in mice expressing mutant human DISC1 (80) | Ventricular enlargement (73) |
|
| ||
| Neurocognitive abnormalities | ||
|
| ||
| Working memory deficit | Working memory and executive function deficits (81) | Working and short-term memory deficits (73); impaired recognition memory (82) |
|
| ||
| Behavioral abnormalities | ||
|
| ||
| Latent inhibition deficit | Latent inhibition deficit, reversed with antipsychotic treatment (83) | Latent inhibition deficit (84) |
| Prepulse inhibition deficit, corrected with antipsychotic treatment | Prepulse inhibition deficit, corrected with antipsychotic treatment (83) | Prepulse inhibition deficit, corrected with chronic nicotine treatment (73) |
| Deficit in open field exploration | Hyperactivity in open field (males only) (71) | Increased baseline motor activity in open field (85) |
| Social interaction deficit | Alterations in social interaction (males only) (71) | Reduced social affiliative behavior (86); abnormal social dyadic interactions, including increased aggression (87) |
a
Reviewed in detail in Patterson (56).
b
Findings are from mutant mouse model unless otherwise noted.
c
Findings are from a heterozygous neuregulin-1 mutant mouse model unless otherwise noted.