Fetal domoic acid exposure affects lateral amygdala neurons, diminishes social investigation and alters sensory-motor gating

Abstract

Domoic acid (DA) is an algal neurotoxin that accumulates in marine fish and shellfish. DA can move across the placenta and concentrate in amniotic fluid, which can be swallowed during late gestation. DA also transfers to infants via milk. Preclinical studies to determine effects of developmental DA expose have primarily involved DA exposure during the postnatal period and little is known about late CNS effects following prenatal DA. In the present study, we tested the hypothesis that prenatal exposure of FVB mice to low levels of DA would result in diminished social interaction and sensory motor gating associated with alterations in parvalbumin immunoreactivity in relevant brain regions undergoing development during and following DA exposure. In addition to parvalbumin, we stained with NeuN for a neuronal specific nuclear protein to determine if neuronal loss followed prenatal DA exposure. A single moderate dose of DA administered during gestation produces diminishes social investigation and alters sensorimotor gating, behavioral effects more pronounced in males than females. These behavioral changes were associated with discrete alterations in the parvalbumin-positive subtype of GABAergic neurons in the dentate gyrus and lateral amygdala.

Keywords: Parvalbumin; Prepulse inhibition; Social investigation.

Fig. 1

Prenatal DA exposure impairs social interactions in adolescent male, but not female, mice at PD25 (A) and PD35 (B). *p < 0.05. All data are presented as the mean ± SEM.

Fig. 2

Prenatal DA exposure reduces USVs in male, but not female, adolescent mice at PD35 (B) but not at PD25 (A). *p < 0.05. All data are presented as the mean ± SEM.

Figure 3. Pre-Pulse inhibition (PPI) of the startle response in prenatal saline- and domoic acid-treated mice

Acoustic startle responses following a 110 decibel pulse preceded by pre-pulses of (A) 70, (B) 75, and (C) 80 decibels. *p < 0.05 indicates a significant decrease () in PPI in DA-treated male mice compared to SA-treated male mice.

Figure 4. Parvalbumin-positive cells in the lateral amygdala and dentate gyrus

(A) There was an overall increase in the number of parvalbumin-positive cells in DA- (males and females) compared to SA- (males and females) treated mice. (B) In the dentate gyrus, males showed a greater number of parvalbumin positive cells compared to females. This main effect of sex was primarily driven by a greater number of parvalbumin expressing cells in DA-treated males compared to DA-treated females. Representative images of parvalbumin positive cells in the lateral amygdala (C) and dentate gyrus (D). ^ indicates an overall main effect of prenatal treatment (p < 0.05). * indicates significant difference between DA females and DA males.

Figure 5. NeuN-positive cells in the prelimbic cortex

No differences were found for the number of NeuN-positive cells in the prelimbic cortex between male and female DA- or SA-treated mice.