Perinatal Nutritional Iron Deficiency Impairs Noradrenergic-Mediated Synaptic Efficacy in the CA1 Area of Rat Hippocampus ,

Abstract

Many studies have shown that perinatal nutritional iron deficiency (ID) produces learning impairments in children. Research has also shown that catecholamines like epinephrine and norepinephrine play a pivotal role in the consolidation of memories. In this study, we sought to determine if perinatal ID impairs the following: 1) noradrenergic synaptic function in the hippocampus; and 2) several forms of hippocampus-dependent fear learning. Electrophysiological brain slice methods were used to examine noradrenergic-mediated synaptic efficacy in the CA1-hippocampus of rats that were subjected to perinatal ID or control (CN) diets. Rats were fed ID (3 mg Fe/kg) or CN (45 mg Fe/kg) diets on gestational d 14. These diets were maintained until postnatal d (P) 12 after which all rats were switched to the CN diet. Hippocampal slices were prepared between P26 and P30. The noradrenergic agonist isoproterenol (ISO) (1, 2, or 4 micromol) was used to induce modulatory increases in synaptic efficacy in the hippocampal slices. CN slices showed a long-lasting increase in synaptic efficacy as the result of ISO perfusion in the slice bath, whereas ID slices did not show increases in synaptic efficacy as the result of ISO perfusion. ID and CN groups did not differ when ISO was perfused through slices from adult rats (P61). Both young and adult ID rats showed reduced levels of hippocampus-dependent fear learning compared with the young and adult CN rats. Together, these findings suggest that ID may impair early forms of noradrenergic-mediated synaptic plasticity, which may in turn play a role in adult learning deficits.

Iron deficiency on neuronal function

“…A recent study showed that rats deprived of iron in the perinatal period, acquired a diminished emotional response to the contextual fear conditioning compared with control rats; while the anxiety related to innate emotional responses, showed no differences between the groups (McEchron et al 2010). Because both emotional responses, acquired and innate, possess different neurobiological substrates, the data suggest that ID differentially affects hippocampus and others brain areas.…”

“…This study examined the effect of isoproterenol (ISO), a b-adrenergic agonist, whose application in the bath produces a long-lasting potentiation of the field recordings and population spikes in hippocampal area CA1 (Gelinas and Nguyen 2005). Hippocampal slices from rats exposed to perinatal ID, did not show enhanced synaptic responses while the control animals did (McEchron et al 2010). In the previous section we discussed evidence supporting the impact of ID on the noradrenergic system .…”

“…A recent study explored the effect of the ID in rats on synaptic efficacy mediated by noradrenergic agonists (McEchron et al 2010). This study examined the effect of isoproterenol (ISO), a b-adrenergic agonist, whose application in the bath produces a long-lasting potentiation of the field recordings and population spikes in hippocampal area CA1 (Gelinas and Nguyen 2005).…”

“…Furthermore, it has been well established that hippocampal-dependent memory processes such as recognition memory and fear conditioning are strongly affected by perinatal ID (Lukowski et al 2010) (Carlson et al 2009;Gewirtz et al 2008;Hernandez-Martinez et al 2011;Lukowski et al 2010;McEchron et al 2005;McEchron et al 2010;Rao et al 2011;Schmidt et al 2007;Siddappa et al 2004).…”

Issues in the Timing of Integrated Early Interventions: Contributions from Nutrition, Neuroscience, and Psychological Research

“…Rodent models of gestational/lactational vs postnatal dietary iron deficiency reveal variable impairments in spatial navigation, trace fear conditioning, and procedural memory, all consistent with functional and structural abnormalities in the hippocampus and striatum, as well as abnormalities in myelin formation and monoamine regulation based on the timing of the deficiency. [31][32][33][34][35][36][37][38][39] A differential timing effect is also seen in rhesus monkeys, where late gestational iron deficiency results in a less fearful and more impulsive animal, while postnatal iron deficiency results in a more inhibited and anxious one. 40 …”