Abstract
The signal transducer and activator of transcription 5 (STAT5) is a transcription factor recruited by numerous cytokines. STAT5 is important for several physiological functions, including body and tissue growth, mammary gland development, immune system and lipid metabolism. However, the role of STAT5 signaling for brain functions is still poorly investigated, especially regarding cognitive aspects. Therefore, the objective of the present study was to investigate whether brain STAT5 signaling modulates learning and memory formation. For this purpose, brain-specific STAT5 knockout (STAT5 KO) mice were studied in well-established memory tests. Initially, we confirmed a robust reduction in STAT5a and STAT5b mRNA levels in different brain structures of STAT5 KO mice. STAT5 KO mice showed no significant alterations in metabolism, growth, somatotropic axis and spontaneous locomotor activity. In contrast, brain-specific STAT5 ablation impaired learning and memory formation in the novel object recognition, Barnes maze and contextual fear conditioning tests. To unravel possible mechanisms that might underlie the memory deficits of STAT5 KO mice, we assessed neurogenesis in the hippocampus, but no significant differences were observed between groups. On the other hand, reduced insulin-like growth factor-1 (IGF-1) mRNA expression was found in the hippocampus and hypothalamus of STAT5 KO mice. These findings collectively indicate that brain STAT5 signaling is required to attain normal learning and memory. Therefore, STAT5 is an important downstream cellular mechanism shared by several cytokines to regulate cognitive functions.
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Acknowledgements
We thank Ana M.P. Campos, Amanda de Alencar, Dr. Claudia P. Figueiredo and Dr. Miriam F. Suzuki for the technical assistance, and Dr. Lothar Hennighausen for kindly providing the STAT5a/b-flox mice.
Funding
Work in JDJr’s lab was funded by the São Paulo Research Foundation (FAPESP) (2012/24345-4, 2012/02388-3, 2014/11752-6, 2015/10992-6, 2016/09679-4, 2016/20897-3 and 2017/02983-2). FGF was funded by grants from Alzheimer Society of Canada, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) and National Institute for Translational Neuroscience.
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Furigo, I.C., Melo, H.M., Lyra e Silva, N.M. et al. Brain STAT5 signaling modulates learning and memory formation. Brain Struct Funct 223, 2229–2241 (2018). https://doi.org/10.1007/s00429-018-1627-z
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DOI: https://doi.org/10.1007/s00429-018-1627-z