Depression-Associated Gene Negr1-Fgfr2 Pathway Is Altered by Antidepressant Treatment

摘要

The gene has been significantly associated with major depression in genetic studies. encodes for a cell adhesion molecule cleaved by the protease Adam10, thus activating Fgfr2 and promoting neuronal spine plasticity. We investigated whether antidepressants modulate the expression of genes belonging to pathway in Flinders sensitive line (FSL) rats, in a corticosterone-treated mouse model of depression, and in mouse primary neurons. and were the genes mostly affected by antidepressant treatment, and in opposite directions. was down-regulated by escitalopram in the hypothalamus of FSL rats, by fluoxetine in the hippocampal dentate gyrus of corticosterone-treated mice, and by nortriptyline in hippocampal primary neurons. mRNA was increased by nortriptyline administration in the hypothalamus, by escitalopram in the hippocampus of FSL rats, and by fluoxetine in mouse dorsal dentate gyrus. Similarly, nortriptyline increased expression in hippocampal cultures. expression was increased by nortriptyline in the hypothalamus of FSL rats and in hippocampal neurons. , another IgLON family protein, increased in mouse dentate gyrus after fluoxetine treatment. These findings suggest that pathway plays a role in the modulation of synaptic plasticity induced by antidepressant treatment to promote therapeutic efficacy by rearranging connectivity in corticolimbic circuits impaired in depression.