Impaired learning and memory and altered hippocampal neurodevelopment resulting from interleukin-2 gene deletion

Interleukin-2 (IL-2), the protypical T cell growth factor and immunoregulat ory cytokine produced by lymphocytes, has been implicated as a brain neurot rophic factor and neuromodulator, The consequences of the absence of endoge nous IL-2 on brain development and function were unknown. Brain IL-2 recept ors are enriched in the hippocampal formation, an area critical for the acq uisition and consolidation of spatial learning and memory, Thus, we tested the hypothesis that mice lacking IL-2 would exhibit alterations in hippocam pal-dependent learning and neurodevelopment, Compared with C57BL/6-IL-2(+/) wild-type mice, we observed that C57BL/6-IL-2(-/-) gene knockout mice had markedly impaired spatial learning and memory in the Morris water maze. No significant deficits in parameters of learning and memory performance were found in severe combined immunodeficient (SCID) mice (C57BL/6scid), howeve r, suggesting that the impaired spatial learning and memory exhibited by IL -2 knockout mice is not attributable to generalized immunodeficiency result ing from the absence of endogenous IL-2. Examination of other domains of be havioral performance showed that the IL-2 knockout and wild-type mice did n ot differ in measures of fearfulness or locomotor activity in an elevated p lus maze, or in reflexive startle responses to auditory stimuli-although pr epulse inhibition of acoustic startle (PPI) was increased significantly in IL-2 knockout mice. The spatial learning and memory impairment in IL-2 knoc kout mice was accompanied by reductions in hippocampal infrapyramidal mossy neuronal fiber length, a factor shown previously to correlate positively w ith spatial learning ability, These findings indicate that, in addition to being a pivotal cytokine in immune regulation, IL-2 may play a role in the development and regulation of brain neurons involved in spatial learning an d memory. J, Neurosci, Res. 56:441-446, 1999, (C) 1999 Wiley-Liss, Inc.