doctoralThesis
Estresse pré-natal: efeitos em longo prazo no comportamento e no balanço dos metabólitos do triptofano
Fecha
2020-09-24Registro en:
MOURA, Clarissa de Almeida. Estresse pré-natal: efeitos em longo prazo no comportamento e no balanço dos metabólitos do triptofano. 2020. 133f. Tese (Doutorado em Psicobiologia) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2020.
Autor
Moura, Clarissa de Almeida
Resumen
Prenatal stress (PNS) directly interferes with fetal programming, a principle by which
the mother's endocrine and metabolic environment can generate long-term
consequences in adult offspring. Among the potential neurochemical pathways affected
by PNS, the tryptophan metabolism by the kynurenine pathway is still poorly
investigated. This study sought to investigate the behavioral and neurochemical
consequences of PNS, with an emphasis on monoamines and metabolites of the
kynurenine pathway, in the adult offspring of mice exposed to PNS. Pregnant females
of Swiss mice were subjected to the restraint stress associated with intense light three
times a day during the last week of gestation (days 14-21). The adult offspring of males
and females submitted to PNS underwent behavioral tests, including open field, object
recognition task, elevated plus maze, social interaction and tail suspension test. For the
neurochemical stage, the adult offspring were euthanized and their brains dissected in
order to quantify the levels of tryptophan, quinolinic acid (QA), kynurenine, 5-
hydroxyindole acetic acid (5-HIAA), serotonin (5-HT), dopamine and noradrenaline in
the hippocampus and brainstem, using the mass spectrometry technique. The prefrontal
cortex (PFC) and hippocampus of the offspring were also dissected in order to evaluate
the gene expression of the following enzymes: indoleamine 2,3-dioxigenase (IDO),
kynurenine monoxygenase (KMO) and kynurenine -aminotransferase 3 (KYAT3),
through the real-time PCR technique. The results revealed that the adult offspring
submitted to the PNS presented: (1) impairment in the object recognition task in the
male and female offspring, with the latter being associated with the estrous cycle; (2)
hyperactivity of the male offspring, accessed by the greater total distance travelled in
the open field, as well as longer time spent in the closed arms in the elevated plus maze
test, suggesting an anxious phenotype, with no changes in monoamine levels, but with
changes in metabolites of the quinurenine pathway, defined by higher levels of QA in
the hippocampus and brainstem and higher levels of kynurenine and tryptophan
exclusively in the hippocampus, (3) increased immobility in the tail suspension test by
the female offspring, suggesting a depressive profile, influenced by the phases of the
estrous cycle, and associated with lower levels of 5-HT in the hippocampus and greater
activity of 5-HT in the hippocampus and brain stem, (4) alteration in the gene
expression of enzymes related to the kynurenine pathway, so that PNS females had
higher expression of KYAT3 in the hippocampus and IDO in the PFC, while the male
offspring showed reduced levels of KMO in the PFC. In conclusion, this study revealed
a sex dependent behavioral and neurochemical profile as a consequence of late PNS in
the mice offspring, evaluating the balance of tryptophan metabolites as a key point.