Abstract
Elevated glucocorticoid level in the early postnatal period is associated with glucocorticoid therapy prescribed at preterm delivery most often has severe long-lasting neurodevelopmental and behavioural effects. Detailed molecular mechanisms of such programming action of antenatal glucocorticoids on behaviour are still poorly understood. To address this question we studied neurotrophins: Bdnf, Nt-3, Ngf and their receptors: p75ngfr, Sorcs3 expression changes after subcutaneous dexamethasone (DEX) 0.2 mg/kg injection to P2 rat pups. Neurotrophins expression level was studied in the hippocampus (HPC). Disturbances in these brain regions have been implicated in the emergence of multiple psychopathologies. p75ngfr and Sorcs3 expression was studied in the brainstem—region where monoamine neurons are located. Immunohistochemically P75NTR protein level changes after DEX were investigated in the brainstem Locus Coereleus norepinephrine neurons (NE). In the first hours after DEX administration elevation of neurotrophins expression in HPC and decline of receptor’s expression in the NE brainstem neurons were observed. Another critical time point during maturation is adolescence. Impact of elevated glucocorticoid level in the neonatal period and unpredictable stress (CMUS) at the end of adolescence on depressive-like behaviour was studied. Single neonatal DEX injection leads to decrease in depressive-like behaviour, observed in FST, independently from chronic stress. Neonatal DEX administration decreased Ntf3 and SorCS1 expression in the brainstem. Also Bdnf mRNA level in the brainstem of these animals didn’t decrease after FST. CMUS at the end of adolescence changed p75ngfr and SorCS3 expression in the brainstem in the animals that received single neonatal DEX administration.
Highlights
Period of life is crucial for the proper organism development especially the brain and nervous s ystem[1,2,3]
Disturbances of neurotrophins expression in the hippocampus during early neonatal period by glucocorticoids could have long-lasting programmable effects on behaviour, memory and depression. To answer this question we studied neurotrophins mRNA Ngf, Bdnf, Nt-3 expression level changes in the hippocampus (HPC) after single subcutaneous dexamethasone injection to P2 rat pups
Bdnf (F(8,50) = 11.129, p < 0.05, n = 4–13) and Nt-3 mRNA level had increased 6 h after DEX administration, but Bdnf mRNA level was elevated for longer lime, till 120 h after injection
Summary
Period of life is crucial for the proper organism development especially the brain and nervous s ystem[1,2,3]. We are far from detailed and systemic understanding of GC influence on neurotrophins and their receptors expression in the neonatal brain, especially recently discovered (sorcs[1,2,3]). These signaling molecules are synthesized in the cells as a proforms, which undergoes proteolytic cleavage to the mature form 34. In this research we studied Bdnf expression in the hippocampus and p75ngfr receptor expression in the brainstem after single dexamethasone injection at P2 Another aspect of the study was modulation of elevated glucocorticoids level in neonatal periods with stress during adolescence, which could have paradoxical and opposite results on memory and behaviour at the same time. After chronic mild unpredictable stress during late adolescence period P45-P60 p75ngfr and Sorcs[3] expression in the brainstem were studied in comparison with acute stress situation and non-stress animals on the background of neonatal DEX administration
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