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Monoamine metabolism in the central nervous system is altered by dietary iron deficiency, with a stronger effect seen during the active than rest span of the circadian cycle. In this report, we examined changes in intracellular and extracellular monoamine levels, synthetic enzymes, transporter and receptor densities, and responses to amphetamine-induced dopamine (DA) efflux in iron-deficient and iron-sufficient mice. Extracellular striatal DA levels were 15-20% higher in all groups during the active dark phase compared to the inactive light phase, with correspondingly lower dopamine transporter (DAT) and higher tyrosine hydroxylase levels. Iron deficiency decreased DAT density by 20% and 28% in the light and dark phases, respectively, and elevated the DOPAC/DA ratio only in the dark, indicating that iron deficiency does interact with the normal diurnal cues for cyclicity. Enhanced DA efflux after amphetamine stimulation indicates no limitation on monoamine synthesis and release and is consistent with altered synaptic efficacy and perhaps recycling of DA in iron deficiency. These experimental findings provide new evidence that brain iron insufficiency does have a differential effect on the DA system at different biological times of the day and night and may be causally related to the phasic motor symptoms observed in Restless Legs Syndrome. [ABSTRACT FROM AUTHOR]

Scant information is available on the diurnal variation of peripheral neurotrophic factors, including brain-derived neurotrophic factor (BDNF), in human beings. We explored plasma and serum BDNF levels at three different clock times in a study of 28 healthy subjects of both sexes. Statistically significant diurnal variation in plasma BDNF level was detected in men, with the peak at 08:00 h and nadir at 22:00 h. At this time, the plasma BDNF concentration of men was significantly lower than that of women (p=.02). However, no diurnal variation was found either in plasma BDNF of women, in either the follicular or luteal phases of the menstrual cycle, or in serum BDNF level in both men and women. These findings support the concept of rhythmic variation in plasma BDNF regulation that seems to be sex-related. (Author correspondence: dmarazzi@psico.med.unipi.it) [ABSTRACT FROM AUTHOR]