Microglial response to the neurotoxicity of 6-hydroxydopamine in neonatal rat cerebellum.
Depletion of noradrenaline in newborn rats by 6-hydroxydopamine (6-OHDA) affects the postnatal development and reduces the granular cell area in the neocerebellum (lobules V-VII). During the first postnatal month, Bergmann glial fibers guide the migration of immature granule cells to the internal granule cell layer. Microglia and Bergmann glia may play an important role in this process, but the exact mechanism behind this phenomenon is not known. We studied the effect of systemic administration of 6-OHDA on the expression and localization on microglia and Bergmann glia in the neonatal cerebellum by immunohistochemistry. In the neocerebellum, 6-OHDA treatment caused a significant increase in the number of activated microglia. The increase was observed mainly in the granule cell layer and the cerebellar medulla. Bergmann glial cells in treated brains were abnormally located, did not form intimate associations with Purkinje cells, and the glial fibers were structurally different. Our findings indicate that a noradrenergic influence may be necessary for the normal maturation and migration of granule cells, and abnormal migration may be the result of Bergmann glia destruction and the activation of microglia. Activated microglia in the granule cell layer may be used as a marker for an injured cerebellar area.
Podkletnova
I
I
University of Tampere, Medical School, PO Box 607, 33101, Tampere, Finland. Ilirpo@uta.fi
Rothstein
J D
JD
Helén
P
P
Alho
H
H
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D037102:Lectins / Q000493:pharmacokinetics; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology; D037121:Plant Lectins; D051381:Rats; D017207:Rats, Sprague-Dawley; D013565:Sympatholytics / Q000494:pharmacology
D015415:Biomarkers; C045475:Griffonia simplicifolia lectins; D037102:Lectins; D009498:Neurotoxins; D037121:Plant Lectins; D013565:Sympatholytics; D016627:Oxidopamine; D009638:Norepinephrine