Effects of Iron Deficiency on Serotonin Uptake In Vitro by Rat Brain Synaptic Vesicles

Abstract

The effects of moderate and severe degrees of iron deficiency on brain and liver nonhaem iron levels and 5-hydroxytryptamine (serotonin; 5-HT) uptake by synaptic vesicles in vitro were investigated in experimental rats. Data obtained suggested that in both moderate and severe forms of iron deficiency, 5-HT uptake by brain synaptic vesicles is decreased and is accompanied by a reduction in brain and liver nonhaem iron levels. On repletion with iron for 4 weeks, the deficient group of rats showed a normalisation of 5-HT uptake by synaptic vesicles and liver nonhaem iron content, whereas the brain nonhaem iron concentration still showed a significant deficit. The data thus suggest that changes in the uptake of 5-HT by brain synaptic vesicles that accompany iron depletion and repletion are more rapid than changes in the total nonhaem iron concentration in the brain. The observation that 5-HT uptake by brain synaptic vesicles is decreased in iron deficiency suggests a probable role for iron in 5-HT storage in rat brain.

Biochemical Basis for the Manifestations of Iron Deficiency

“…Analogous results for serotonin (SHT) were reported by Kaladhar & Rao (93). SHT is also an important neurotransmitter whose function is linked to slow-wave sleep.…”

“…This deficit is unusual in that it cannot be reversed, even after other manifestations of iron deficiency have been corrected by iron treatment. The physiological implications of this finding remain uncertain since the relatively few other biochemical manifestations of iron deficiency in brain that have been described are reversed with iron administration (83,92,93).…”

“…Although, iron deficiency appears to affect systemic cate cholamine metabolism, the changes in the brain seem less profound. The notable exceptions, to be described in more detail, involve not synthesis or catabolism, but an impairment in the binding of DA to the D2 receptor of the caudate nucleus (92) and of SHT to brain synaptic vesicles (93).…”

Iron deficiency: Differential effects on monoamine transporters

“…Serotonin transporters affected by iron deficiency in males included those in the olfactory tubercle, lateral parabrachial nucleus, superficial gray of the superior colliculus, optic tract, nucleus accumbens and cerebral cortex (Kaladhar 1982(Kaladhar ,1983. For the first three of these areas, iron repletion failed to restore the values to normal.…”

Genetically Epilepsy‐Prone Rats are Characterized by Altered Tissue Trace Element Concentrations

“…Low brain iron in the seizure-prone strain of rats is potentially very significant because brain has a variety of iron-containing proteins involved in oxidative metabolism; an impairment in oxidative metabolism could have a serious impact on neuronal function. As reported in a recent review of trace elements in brain metabolism (Prohaska, 1987), efforts to study neurotransmitter metabolism in iron deficiency have been few and inconclusive, although roles for iron in dopamine receptor binding (Youdim et al, 1983) and in serotonin storage (Kaladhar and Rao, 1982) have been suggested.…”