IL-2 deficiency results in altered septal and hippocampal cytoarchitecture: relation to development and neurotrophins.
We have found previously that brain IL-2 receptors are enriched in the hippocampal formation, and that loss of this cytokine results in cytoarchitectural alterations in the hippocampus and septum and related behavioral changes in IL-2 knockout (IL-2 KO) mice. These alterations included decreased cholinergic somata in the medial septum/vertical limb of the diagonal band of Broca (MS/vDB) and decreased distance across the infrapyramidal (IP) granule cell layer (GCL) of the dentate gyrus (DG). To extend our previous findings, several experiments were conducted comparing IL-2 KO mice and wild-type littermates to determine (1) whether the GABAergic projection neurons of IL-2 KO mice in this region were also affected; (2) if the reduction in septal cholinergic projection neurons found in adult IL-2 KO mice is present at weaning (and prior to the development of peripheral autoimmune disease); and (3) if loss of IL-2 may result in changes in the neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), involved in maintenance of hippocampal neurons. No differences in GABAergic neurons in the MS/vDB were found in adult mice, and the reduction in cholinergic neurons seen in adult IL-2 KO mice was not found in animals at postnatal day 21. The number of neurons in the IP-GCL was also significantly reduced. Compared to wild-type mice, IL-2 KO mice had significantly reduced concentration of BDNF protein and increased concentrations of NGF. These data suggest that the septohippocampal neuronal loss in IL-2 KO mice is selective for the cholinergic neurons and appears to be due to a failure in neuronal maintenance/survival that may be, in part, associated with changes in neurotrophins.
Beck
Ray D
RD
McKnight Brain Institute, L4-118, University of Florida College of Medicine, P.O. Box 100256, Gainesville, FL 32610-0256, USA.
King
Michael A
MA
Ha
Grace K
GK
Cushman
Jesse D
JD
Huang
Zhi
Z
Petitto
John M
JM
D000818:Animals; D001923:Brain Chemistry / Q000235:genetics / Q000276:immunology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000378:metabolism; D002452:Cell Count; D002795:Choline O-Acetyltransferase / Q000096:biosynthesis; D018891:Dentate Gyrus / Q000254:growth & development / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020667:Diagonal Band of Broca / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D006624:Hippocampus / Q000254:growth & development / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007376:Interleukin-2 / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020932:Nerve Growth Factor / Q000096:biosynthesis*; D009474:Neurons / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010320:Parvalbumins / Q000096:biosynthesis; D017966:Pyramidal Cells / Q000254:growth & development / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020665:Septum of Brain / Q000254:growth & development / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis
D019208:Brain-Derived Neurotrophic Factor; D007376:Interleukin-2; D010320:Parvalbumins; D005680:gamma-Aminobutyric Acid; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase