Cytokines Effects on Learning and Memory
One of the earliest observations suggesting that cytokines could influence cognitive function in humans came from cancer studies where IL-2 immunotherapy was used to treat some types of neoplasias. Treatment with this pivotal immunoregulatory cytokine induced prominent, untoward neuropsychiatric side effects with patients exhibiting cognitive dysfunction (1,2). Seminal basic studies showed that peripheral immunization led to activation of hypothalamic neurons, and also demonstrated that lymphocytes had the capacity to produce neuropeptides (for reviews see 3,4). This sparked considerable growth in this area of research, and it is now well established that cytokines can communicate with endocrine and brain cells. Just as researchers were surprised several decades ago to discover that digestive peptides such as CCK and VIP were in the brain, cytokines and their receptors once believed to be derived solely from lymphoid cells have been identified in normal brain. They function as neuromodulators and neurotrophic factors, as well as mediators of immune-like responses involved in CNS pathology. As described in subsequent sections of the chapter, in the case of IL-2, a number of basic investigations have shown that this cytokine can modify various neurobiological processes associated with learning and memory.
KeywordsQuantitative Trait Locus Spatial Learning Contextual Fear Conditioning Neurobiological Process Conditioning Quantitative Trait Locus
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- 6.Maier, S.F. and Watkins, L.R. Cytokines for psychologists: Implications of bidirectional immune-to-brain communication for understanding behavior, mood and cognition. Psychol Rev. 1998; 83–107Google Scholar
- 16.Gibertini, M., Newton, C., Klein, T.W., et al. Legionella pneumophila-induced visual learning impairment reversed by anti-interleukin-1 beta. Proceed. Soc. Exp. Biol. Med. 1995; 210:7–11.Google Scholar
- 20.Capuron, L., Ravaud, A., Radat, F., et al. Effects of interleukin-2 and alpha interferon cytokine immunotherapy on the mood and cognitive performance of cancer patients. Neuroimmunomodul. 1998; 22: 9.Google Scholar
- 28.Jankowsky, J., Patterson, P. Cytokine and growth factor involvement in long-term potentiation. Mole. Cell. Neurosci. 1999; 14:273–286.Google Scholar
- 38.Ader, R., Felten, D., Cohen, N. (Eds.) Psychoneuroimmunology, 3rd Edition, Academic Press, San Diego, CA, 2001.Google Scholar
- 41.Hanisch, U.K., Seto, D., Quirion, R. Modulation of hippocampal acetylcholine release: a potent central action of interleukin-2. J. Neurosci. 1993; 12: 3368–3374.Google Scholar
- 52.Petitto, J.M. “Behavioral genetics and immunity”. In Psychoneuroimmunology, Third Edition. Ader, Felten and Cohen eds. San Diego, CA: Academic Press, 2001, pp. 173–186.Google Scholar
- 56.Nishiyama, N. Thymectomy-induced deterioration of learning and memory. Cell. Mole. Biol. 2001;47:161–165.Google Scholar