Delayed-onset Deficit Research Articles

Heroin neuroteratogenicity: delayed-onset deficits in catecholaminergic synaptic activity

Prenatal heroin exposure evokes neurochemical and behavioral deficits that, in part, reflect disruption of septohippocampal cholinergic function. In earlier studies, we found that cholinergic synaptic defects involve primary changes in cell signaling proteins that are shared by other transmitter systems. In the current study, we determined whether heroin also targets noradrenergic and dopaminergic inputs that operate through the same signaling cascades. Mice exposed to prenatal heroin showed significant deficits in norepinephrine and dopamine levels and much more pronounced effects on neurotransmitter turnover, an index of synaptic activity. Adverse effects were not present in the immediate postnatal period but rather emerged just before weaning and worsened subsequently. By young adulthood, the most highly-affected regions (hippocampus, cerebral cortex) displayed almost complete inactivation of noradrenergic and dopaminergic tonic activity. These effects arise after prior deficits in cell signaling are discernible, suggesting that the presynaptic effects are secondary to actions on signal transduction cascades shared by numerous neurotransmitter inputs and targeted by other neuroteratogens. These results may explain why apparently unrelated developmental neurotoxicants may ultimately produce a common set of neurochemical and behavioral anomalies.

Delayed-Onset Deficits in Verbal Encoding Strategies Among Patients With Mild Traumatic Brain Injury.

Knowledge obtained from longitudinal animal models was used to predict the course of verbal memory deficits in 19 concussed patients and 19 control patients who were given versions of the Hopkins Verbal Learning Test--Revised at 2 hr, 48 hr, and 1 week postconcussion. The physiological literature suggests that concussed patients should exhibit a decline in performance from 2 hr to 48 hr postconcussion on a measure of complex memory strategies. Consistent with this hypothesis, mixed-factor analysis of covariance revealed that concussed patients used less semantic clustering strategies than control patients at 48 hr postconcussion, whereas minimal differences were found at 2 hr postinjury. Furthermore, a chi-square analysis showed that a significant number of concussed patients experienced a decline in the number of semantic clusters they used from 2 hr to 48 hr. No differences were found between the groups at the 1-week testing session.