Table 3.
Animal studies demonstrating that in utero exposure to maternal brain-reactive antibodies can permanently alter the brain, leading to behavioral and cognitive deficits.
| Target | Animal model | Characteristics | References |
|---|---|---|---|
| Cerebellar Purkinje cells and brainstem neurons | Passive transfer: daily maternal serum injections into pregnant mice from E10 to E17 | Decreased exploration Altered motor coordination Cerebellar metabolite abnormalities. | (79) |
| Unknown | Passive transfer: IV injections of pooled maternal IgG to pregnant rhesus macaque on gestation days 27, 41 and 55 | Hyperactivity Increased stereotypies | (92) |
| LDH/STIP1/CRMP1 (antigens of molecular weights 37 and 73 kDa) | Passive transfer: single IV injection of purified maternal IgG into pregnant mice on E12 | Delayed pre-weaning motor and sensory development. Increased number of USVs on P8 Males had a longer total USV duration on P8 Increased anxiety-like behaviors in males Slightly shorter social interaction in males | (93) |
| Passive transfer: IV maternal IgG injection into rhesus macaque throughout pregnancy | Aberrant social behaviors Enlarged brain volume due to increases in white matter in male offspring. | (94) | |
| Single intraventricular maternal IgG injection into E14 mouse embryos | Increased repetitive behaviors measured as digging in the marble test and grooming Impaired social interactions | (95) | |
| Single intraventricular maternal IgG injection into E14 or E16 mouse embryos | Greater number of proliferating stem cells in the SVZ of the neocortex and ganglionic eminence Increased adult brain size and weight Increased adult cortical neuron some volume | (96) | |
| Single intraventricular maternal IgG injection into E14 mouse embryos | Decreased basal dendritic arborization in layer V pyramidal neurons of the frontal cortex Reduced the dendritic spine number and density in several brain regions | (97) | |
| Endogenous production: female mice were immunized prior to pregnancy with antigenic peptides recognized by anti- LDH/STIP1/CRMP1 antibodies. | Impaired social interactions Impaired social communication measured by USVs neonatally and as adults. Increased repetitive behaviors measured as grooming | (98) | |
| Unknown | Passive transfer: daily IP injections of pooled maternal IgG to pregnant mice from E13 to E18. | Hyperactivity Increased anxiety Impaired social interactions Increased IL-12 levels on E16 and microglia activation on E18 fetal brains. | (99) |
| Passive transfer: daily IP injections of pooled maternal IgG to pregnant mice from E13 to E18. | Greater cell proliferation in the SVZ and SGZ post-natally. Decreased cortical cell survival post-natally. | (100) | |
| Caspr2 | Passive transfer: single IV injection of anti-Caspr2 IgG to pregnant mice on E13.5 | Male fetuses: 1. Thinner cortical plate 2. Fewer proliferating cells in the VZ 3. Reduced number of neurons in the entorhinal cortex Adult males: 1. Decreased number of GABAergic neurons in the hippocampus 2. Decreased dendritic arborization and spine density in CA1 pyramidal neurons 3. Increased stereotypic behaviors: increased digging measured as digging in the marble test 4. Impaired flexible learning 5. Impaired social interactions |
(91) |
| DNA and NMDAR | Endogenous production: female mice were immunized prior to pregnancy with a peptide mimetope of DNA. Passive transfer: single IV injection of NMDAR reactive IgG on E14 to pregnant mice | Fetuses: 1. Increased cortical cell death and proliferation 2. Thinner cortical plate • Adults: 1. Decreased cortical neuron size 2. Decreased cortical volume 3. Cognitive impairments in males |
(101) |
| Endogenous production: female mice were immunized prior to pregnancy with a peptide mimetope of DNA. | Increased female fetal death rate | (102) |
E, Embryonic day; IV, intravenous; LDH, lactate dehydrogenase; STIP1, stress-induced phosphoprotein 1; CRMP, collapsing response mediator protein 1; SVZ, subventricular zone; USVs, ultrasonic vocalizations; P, ponstnatal day; IP, intraperitoneal; SGZ, subgranular zone; Caspr2, Contactin-associated protein-like 2; VZ, ventricular zone; NMDAR, N-Methyl-D-aspartate receptor.