Perinatal malnutrition programs sustained alterations in nitric oxide released by activated macrophages in response to fluoxetine in adult rats.
OBJECTIVE
Nutritional restriction during lactation has long-term consequences on the functioning of neuroimmune systems. Receptors and transporter serotonin (5-HT) are present in macrophages and may influence their role. This study evaluated nitric oxide release by alveolar macrophages (AMs) in adult control rats and rats malnourished during lactation in response to different fluoxetine (FLX) concentrations and 5-HT(1A) and 5-HT(1B) agonists at different times.


METHODS
Male Wistar rats were distributed into two groups according to maternal diet during lactation: a control group of 12 rats whose dams had received a 23% protein diet and a malnourished group of 12 rats whose dams had received an 8% protein diet. After weaning, all rats received a 23% protein diet. On the 90th day after birth, nitric oxide (NO) release kinetics was measured in supernatants of AMs cultured with FLX. The NO release following the adjunction of serotoninergic agonists was also quantified.


RESULTS
The malnourished rats weighed less at weaning (control rats = 15.3 +/- 0.4 g, malnourished rats = 11.8 +/- 0.4 g); this difference persisted until 90 days of life (control rats = 355.4 +/- 8.6 g; malnourished rats = 267.8 +/- 7.9 g). In the presence of 10(-6)M FLX, NO release by AMs in control rats was lower. The addition of agonists did not interfere with NO release by AMs in control rats. NO release by AMs from malnourished rats was modified neither by FLX nor by agonists. As a consequence of malnutrition, there were lower numbers of cells and AMs in the bronchoalveolar lavage fluid, and cell viability and NO release by AMs were impaired.


CONCLUSIONS
Nutritional manipulation in the perinatal period seems to interfere with the functional programming of macrophages; it also seems to affect their serotoninergic regulation through adulthood.
Departamento de Nutrição, Centro de Ciências da Saúde, UFPE, Recife, Brazil. wyllatfs@hotmail.com
Wylla T
WT
Ferreira-E-Silva
Bruno A
BA
Galvão
Kelli N
KN
Ferraz-Pereira
Célia B
CB
de-Castro
Raul
R
Manhães-de-Castro
D000818:Animals; D001835:Body Weight / Q000502:physiology; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000494:pharmacology; D006801:Humans; D007107:Immune System / Q000254:growth & development / Q000503:physiopathology; D007228:Infant Nutrition Disorders / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D007231:Infant, Newborn; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013995:Time
D005473:Fluoxetine; D009569:Nitric Oxide; D044282:Receptor, Serotonin, 5-HT1A; D044302:Receptor, Serotonin, 5-HT1B; D012701:Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors