Identifying the Threshold of Iron Deficiency in the Central Nervous System of the Rat by the Auditory Brainstem Response

Abstract

The deleterious effects of anemia on auditory nerve (AN) development have been well investigated; however, we have previously reported that significant functional consequences in the auditory brainstem response (ABR) can also occur as a consequence of marginal iron deficiency (ID). As the ABR has widespread clinical use, we evaluated the ability of this electrophysiological method to characterize the threshold of tissue ID in rats by examining the relationship between markers of tissue ID and severity of ABR latency defects. To generate various levels of ID, female Long-Evans rats were exposed to diets containing sufficient, borderline, or deficient iron (Fe) concentrations throughout gestation and offspring lifetime. We measured hematological indices of whole body iron stores in dams and offspring to assess the degree of ID. Progression of AN ID in the offspring was measured as ferritin protein levels at different times during postnatal development to complement ABR functional measurements. The severity of ABR deficits correlated with the level of Fe restriction in each diet. The sufficient Fe diet did not induce AN ID and consequently did not show an impaired ABR latency response. The borderline Fe diet, which depleted AN Fe stores but did not cause systemic anemia resulted in significantly increased ABR latency isolated to Peak I.The low Fe diet, which induced anemia and growth retardation, significantly increased ABR latencies of Peaks I to IV. Our findings indicate that changes in the ABR could be related to various degrees of ID experienced throughout development.

Iron deficiency without anaemia is a potential cause of fatigue: meta-analyses of randomised controlled trials and cross-sectional studies

“…Animal studies present evidence supporting this hypothesis. Rats exposed to a marginal Fe diet (20 mg/kg) through gestation and weaning exhibited abnormal auditory brainstem responses ( 47 ) . Marginally Fe-deficient rats without decreased Hb showed abnormal behaviour (i.e.…”

Iron as a model nutrient for understanding the nutritional origins of neuropsychiatric disease

“…Additionally, the diameter of myelinated axons is significantly decreased in developmentally ID rats, even in adulthood, suggesting that iron is critical for establishment of myelination (54). This has been noted to correspond functionally with decreased conduction velocity (65).…”

Impairment of the Developing Human Brain in Iron Deficiency: Correlations to Findings in Experimental Animals and Prospects for Early Intervention Therapy

“…Structurally, influences include structural defects in general brain development [48], and more specifically, the development of dendritic length and arborization, and effects on the formation of synapses [44,53,57,58]. A particular focus in many studies has been the effects of changes in the expression level of genes related to the functioning of synaptic transmission [55,59], vascularization [55], and hormones improving metabolism [61]. Studies have also reported on defects in the synthesis of monoaminergic neurotransmitters [46,47,57], and growth factors [48].…”