The absence of a functional thymus is associated with alterations in peripheral and central neurotransmitters and neurotrophins

It is at present well established that there are physiological interactions between the nervous, endocrine, and immune systems. This work focuses on the impact that the lack of a functional thymus has on neurotransmitter and neurotrophin concentrations in the spleen and in defined brain regions, using as a model homozygous Foxn1nu mice. This spontaneous mutation results in defective development of the thymus anlage, and therefore, in lack of mature T cells. The first part of this work shows that Foxn1nu mice have: 1) an increased splenic sympathetic innervation that is maintained during adult life; 2) alterations in noradrenergic and serotonergic neurotransmitters in defined brain regions comparable to those in the spleen; 3) increased density of noradrenergic fibers in the spleen and hypothalamus; 4) increased brain-derived nerve growth factor (BDNF) and neurotrophin-3 (NT-3) concentrations, and BDNF signals in the spleen and hippocampus; 5) marked alterations in the anatomy of the hippocampus; and 6) increased corticosterone blood levels. All these alterations are abolished in Foxn1nu mice reconstituted by thymus transplantation at birth. The second part studied whether the alterations detected in nude mice reflect a more general condition that causally relates the catecholaminergic system with the expression of neurotrophins. The results demonstrate that destruction of noradrenergic neurons by administration of a neurotoxin, results in a permanent or transient denervation that is paralleled by increased or decreased neurotrophin concentrations in the spleen and in the brain and in corticosterone blood levels, depending on the age at which mice are denervated. Taken together, the results reported here indicate that the alterations in neurotransmitters and neurotrophins observed in homozygous Foxn1nu mice are not just an epiphenomenon fortuitously associated with the absence of a functional thymus, but that most likely mature T cells, by acting either directly or indirectly, exert an inhibitory influence on the development of splenic sympathetic innervation and of catecholaminergic and serotonergic mechanisms in the central nervous system. In more general terms, these results provide new evidence that the immune system can affect the nervous and endocrine systems.