title: The role of interleukin-1, interleukin-6, and glia in inducing growth of neuronal terminal arbors in mice.
abstract: After injury to the substantia nigra pars compacta (SNpc), remaining neurons sprout to ensure normal dopamine delivery to the striatum. The consequent striatal reinnervation is highly regulated, with remaining cells sprouting so that density of dopamine terminals returns to normal. Sprouting as a result of injury is accompanied by a strong glial response; however, it is difficult to know whether this response is as a result of the injury or whether it is aiding in the sprouting. The two cytokines interleukin-1 (IL-1) and interleukin-6 (IL-6) are important modulators of the glia response. This study demonstrates their role in regulating the sprouting of dopaminergic neurons and the associated glia response as a means to examine the role of glia in sprouting. Sprouting was induced by 6-hydroxydopamine lesions of the SNpc and by haloperidol treatment (in the absence of injury). In wild-type animals, sprouting in association with microglial and astrocyte proliferation followed partial lesions of the SNpc and haloperidol treatment. Neither treatment evoked sprouting or glia proliferation in the type I IL-1 receptor-deficient mice, whereas in IL-6-deficient mice, both treatments resulted in glial proliferation but not sprouting. We conclude that IL-1 plays a role in modulating glia proliferation and thereby guidance and trophic factors for new fibers, whereas IL-6 may be important in triggering the outgrowth of new fibers. This study demonstrates that these cytokines play an important role in plasticity and regeneration that is separate from the inflammatory response associated with brain injury.
authors.affiliation: Neurosciences Group, Department of Medicine, Monash University, Monash Medical Centre, Clayton 3168, Australia.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Parish
authors.forename: David I
authors.initials: DI
authors.lastname: Finkelstein
authors.forename: Wanida
authors.initials: W
authors.lastname: Tripanichkul
authors.forename: Abhay R
authors.initials: AR
authors.lastname: Satoskar
authors.forename: John
authors.initials: J
authors.lastname: Drago
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Horne
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006220:Haloperidol / Q000494:pharmacology; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D015850:Interleukin-6 / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D016627:Oxidopamine / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D017472:Receptors, Interleukin-1 / Q000172:deficiency / Q000378:metabolism; D053573:Receptors, Interleukin-1 Type I; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol