Changes in the Hippocampal Genes Transcriptome in Depression Model Mice upon Intranasal Exposure to M2 Macrophage Secretome Factors
Shevela E.Y.1, Markova E.V.1,2, Knyazheva M.A.1, Proskurina A.S.3, Efremov Y.R.2,3, Molodtsov V.V.2,4, Seledtsov I.A.4, Ostanin A.A.1, Bogachev S.S.3, Kolchanov N.A.3, Chernykh E.R.1
1Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia
2Novosibirsk National Research State University, Novosibirsk, Russia
3Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
4Softberry Inc., New-York, USA
Abstract. In the current report, the effect of bioactive compounds of the M2 macrophage secretome on transcription of hippocampal genes in mice with a depression-like condition caused by social stress has been investigated. Surgically resected hippocampus was used for mRNA isolation with following RNA sequencing procedures. Comparative analysis of transcriptomes from the control depressive mice treated with physiological saline solution and mice after intranasal administration of M2 macrophages-conditioned medium revealed that remission of the depressive-like state is associated with a significant up- and downregulation of a number of genes, which were found to participate in restoration/regulation of ATP/Adenosine balance. Among the events associated with positive changes in behavioral pattern of depressive mice, the switch of microglial environment from a pro-inflammatory phenotype to an anti-inflammatory one, and subsequent restoration of compromised cannabinoid and glutamatergic transmitter pathways has been predicted.
Key words: ATP, cannabinoid system, glutamate, microglia, neurons, RNAseq.