Depression-Associated Negr1 Gene-Deficiency Induces Alterations in the Monoaminergic Neurotransmission Enhancing Time-Dependent Sensitization to Amphetamine in Male Mice

Autor: Maria Kaare, Mohan Jayaram, Toomas Jagomäe, Katyayani Singh, Kalle Kilk, Kaie Mikheim, Marko Leevik, Este Leidmaa, Jane Varul, Helis Nõmm, Kristi Rähn, Tanel Visnapuu, Mario Plaas, Kersti Lilleväli, Michael K. E. Schäfer, Mari-Anne Philips, Eero Vasar
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Brain Sciences, Vol 12, Iss 12, p 1696 (2022)
Druh dokumentu: article
ISSN: 2076-3425
DOI: 10.3390/brainsci12121696
Popis: In GWAS studies, the neural adhesion molecule encoding the neuronal growth regulator 1 (NEGR1) gene has been consistently linked with both depression and obesity. Although the linkage between NEGR1 and depression is the strongest, evidence also suggests the involvement of NEGR1 in a wide spectrum of psychiatric conditions. Here we show the expression of NEGR1 both in tyrosine- and tryptophan hydroxylase-positive cells. Negr1−/− mice show a time-dependent increase in behavioral sensitization to amphetamine associated with increased dopamine release in both the dorsal and ventral striatum. Upregulation of transcripts encoding dopamine and serotonin transporters and higher levels of several monoamines and their metabolites was evident in distinct brain areas of Negr1−/− mice. Chronic (23 days) escitalopram-induced reduction of serotonin and dopamine turnover is enhanced in Negr1−/− mice, and escitalopram rescued reduced weight of hippocampi in Negr1−/− mice. The current study is the first to show alterations in the brain monoaminergic systems in Negr1-deficient mice, suggesting that monoaminergic neural circuits contribute to both depressive and obesity-related phenotypes linked to the human NEGR1 gene.
Databáze: Directory of Open Access Journals
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