Hippocampal brain derived neurotrophic factor levels are mediated by T cells in response to stress

• Published in: Brain, behavior, and immunity Vol. 49; p. e20
• Main Authors: Clark, S.M, Li, X, Tonelli, L.H
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-10-2015
• Subjects: Allergy and Immunology; Psychiatry
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2015.06.088

Brain derived neurotrophic factor (BDNF) is ubiquitously expressed throughout the central nervous system and is vital for the maintenance of neuronal survival and function. Recent studies examining mRNA levels and total BDNF expression have suggested that the adaptive immune system may contribute to brain homeostasis and neuronal function via modulation of this neurotrophin. Taking into consideration BDNF processing and the opposing roles of pro-BDNF and mature BDNF on synaptic plasticity, we evaluated levels of both BDNF forms in the hippocampus of wild type C57Bl/6 and Rag2-/- mice that underwent stress exposure in the learned helplessness paradigm. Using this model, in conjunction with the reconstitution of Rag2-/- mice with naive T cells, we have shown that T cells modulate BDNF levels and the ratio of mature BDNF to pro-BDNF following exposure to inescapable stress. Compared to wild type mice, Rag2-/- mice displayed elevated levels of pro- and mature BDNF, concurrent with an increase in the mature:pro-BDNF ratio, two hours after stress exposure. Furthermore, adoptive transfer of naive T cells was sufficient to block this increase. Evaluation of BDNF levels after subsequent exposure to escapable stress did not reveal any differences in expression. These findings suggest that T cells modulate hippocampal BDNF levels as part of the development of adaptive processes in response to stress.