Supervisors info:
Κουτσιλιέρης Μιχαήλ, Καθηγητής, Ιατρική, ΕΚΠΑ
Δάλλα Χριστίνα, Επίκουρος Καθηγητής, Ιατρική, ΕΚΠΑ
Τσαρμπόπουλος Αντώνης, Αναπληρωτής Καθηγητής, Ιατρική, ΕΚΠΑ
Summary:
Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are synthetized in the
brain, as well as in peripheral tissues and glands, like the adrenals. Νeurosteroids and
DHEA in particular, play a role in neurodegeneration and neural protection. Moreover,
DHEAS impacts the composition and secretion of catecholamine by the adrenal glands.
However, natural neurosteroids are metabolized in androgens, estrogens or other
metabolites. In order to avoid endocrine actions and improve the anti-apoptotic and
neuroprotective properties of DHEA, novel compounds with analogous properties have
been composed with the positions C3 or C17 modified. Compounds like BNN27, are
called microtrophins and they are designed to mimic the neurotrophic / neuroprotective
properties of DHEA, but not its endocrine properties (androgenic and estrogenic). The
current study took place in the Dep. of Pharmacology at the Medical School of the
National Kapodistrian University of Athens and it included samples from male and
female rat brains which had been injected with two BNN27 (10 and 30 mg/kg, i.p.) or
vehicle, in order to identify potential antidepressant and anxiolytic properties of BNN27.
Rats were subjected to the forced swim test, elevated plus maze, open field and light/dark
tests. BNN27 had no anxiolytic or antidepressant properties, but a mild sedative effect of
BNN27 at high dose in both sexes was identified. The goal of this thesis was the
qualitative and quantitative identification of amino acids neurotransmitters in the brain
areas of the hippocampus and the prefrontal cortex of male and female rats treated with
BNN27 or vehicle. The analysis was conducted through the wet technique of
chromatography of high pressure with an electrochemical detector (HPLC-ED). The
amino acids that were analyzed were asparagine (ASN), glutamic acid (GLU), glutamine
(GLN), taurine (TAU) and gamma-aminobutyric acid (GABA). The statistical analysis,
using a two-way ANOVA, revealed that BNN27 increases the levels of glutamine in the
area of the hippocampus, irrespectively of the dosage and the sex of the animals.
Furthermore, the levels of glutamate in the areas of the hippocampus and the prefrontal
cortex were higher in males than in females. No effect of BNN27was identified in the
rest of the amino acids’ levels. In conclusion, it appears that BNN27 does not exert
anxiolytic or antidepressant properties and it does not influence the levels of
neurotransmitters GABA and glutamate in the brain. However, BNN27 treatment seems
to influence the levels of glutamine and thus indirectly, the glutamatergic system in the
hippocampus. This finding may be linked with BNN’s possible capacity to improve
cognitive function in neurodegenerative disorders.
Keywords:
Neurochemical analysis, Rats, BNN27, Amino acids
