Zinc and glutamine improve brain development in suckling mice subjected to early postnatal malnutrition.
OBJECTIVE
The effect of zinc and glutamine on brain development was investigated during the lactation period in Swiss mice.


METHODS
Malnutrition was induced by clustering the litter size from 6-7 pups/dam (nourished control) to 12-14 pups/dam (undernourished control) following birth. Undernourished groups received daily supplementation with glutamine by subcutaneous injections starting at day 2 and continuing until day 14. Glutamine (100 mM, 40-80 microL) was used for morphological and behavioral studies. Zinc acetate was added in the drinking water (500 mg/L) to the lactating dams. Synaptophysin and myelin basic protein brain expressions were evaluated by immunoblot. Zinc serum and brain levels and hippocampal neurotransmitters were also evaluated.


RESULTS
Zinc with or without glutamine improved weight gain as compared to untreated, undernourished controls. In addition, zinc supplementation improved cliff avoidance and head position during swim behaviors especially on days 9 and 10. Using design-based stereological methods, we found a significant increase in the volume of CA1 neuronal cells in undernourished control mice, which was not seen in mice receiving zinc or glutamine alone or in combination. Undernourished mice given glutamine showed increased CA1 layer volume as compared with the other groups, consistent with the trend toward increased number of neurons. Brain zinc levels were increased in the nourished and undernourished-glutamine treated mice as compared to the undernourished controls on day 7. Undernourished glutamine-treated mice showed increased hippocampal gamma-aminobutyric acid and synaptophysin levels on day 14.


CONCLUSIONS
We conclude that glutamine or zinc protects against malnutrition-induced brain developmental impairments.
Ladd
Fernando V L
FV
Department of Surgery, College of Veterinary Medicine, University of São Paulo, São Paulo, SP, Brazil.
Ladd
Aliny A B L
AA
Ribeiro
Antônio Augusto C M
AA
Costa
Samuel B C
SB
Coutinho
Bruna P
BP
Feitosa
George André S
GA
de Andrade
Geanne M
GM
de Castro-Costa
Carlos Maurício
CM
Magalhães
Carlos Emanuel C
CE
Castro
Ibraim C
IC
Oliveira
Bruna B
BB
Guerrant
Richard L
RL
Lima
Aldo Angelo M
AA
Oriá
Reinaldo B
RB
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D019587:Dietary Supplements; D004359:Drug Therapy, Combination; D005260:Female; D005973:Glutamine / Q000494:pharmacology* / Q000627:therapeutic use; D007774:Lactation; D044342:Malnutrition / Q000097:blood / Q000188:drug therapy*; D051379:Mice; D018977:Micronutrients / Q000097:blood / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D011247:Pregnancy; D013550:Swimming; D016708:Synaptophysin / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects*; D015032:Zinc / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D019345:Zinc Acetate / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018977:Micronutrients; D016708:Synaptophysin; D005973:Glutamine; D005680:gamma-Aminobutyric Acid; D019345:Zinc Acetate; D015032:Zinc