Alterations in septohippocampal cholinergic neurons resulting from interleukin-2 gene knockout.
Interleukin-2 (IL-2) has potent effects on acetylcholine (ACh) release from septohippocampal cholinergic neurons and trophic effects on fetal septal and hippocampal neuronal cultures. Previous work from our lab showed that the absence of endogenous IL-2 leads to impaired hippocampal neurodevelopment and related behaviors. We sought to extend this work by testing the hypotheses that the loss of IL-2 would result in reductions in cholinergic septohippocampal neuron cell number and the density of cholinergic axons found in the hippocampus of IL-2 knockout mice. Stereological cell counting and imaging techniques were used to compare C57BL/6-IL-2(-/-) knockout and C57BL/6-IL-2(+/+) wild-type mice for differences in choline acetyltransferase (ChAT)-positive somata in the medial septum and vertical limb of the diagonal band of Broca (MS/vDB) and acetylcholine esterase (AChE)-labeled cholinergic axons in hippocampal projection fields. IL-2 knockout mice had significantly lower numbers (26%) of MS/vDB ChAT-positive cell bodies than wild-type mice; however, there were no differences in striatal ChAT-positive neurons. Although AChE-positive axon density in CA1, CA3b, the internal, and external blades of the dentate gyrus did not differ between the knockout and wild-type mice, the distance across the granular cell layer of the external blade of the dentate gyrus was reduced significantly in IL-2 knockout mice. Further research is needed to determine whether these outcomes in IL-2 knockout mice may be due to the absence of central and/or peripheral IL-2 during brain development or neurodegeneration secondary to autoimmunity.
Beck
Ray D
RD
McKnight Brain Institute College of Medicine, University of Florida, PO Box 100256, L4-118, Gainseville, FL 32610-0256, USA.
King
Michael A
MA
Huang
Zhi
Z
Petitto
John M
JM
D000818:Animals; D002795:Choline O-Acetyltransferase / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D002799:Cholinergic Fibers / Q000737:chemistry / Q000502:physiology*; D006624:Hippocampus / Q000737:chemistry / Q000502:physiology*; D007376:Interleukin-2 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020665:Septum of Brain / Q000737:chemistry / Q000502:physiology*
D007376:Interleukin-2; D002795:Choline O-Acetyltransferase