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Neonatal 6‐hydroxydopamine treatment affects GABA A receptor subunit expression during postnatal development of the rat cerebellum
Author(s) -
Podkletnova I.,
Alho H.,
Mäkelä R.,
Lüddens H.,
Helén P.,
Korpi E.R.
Publication year - 2000
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/s0736-5748(00)00003-4
Subject(s) - cerebellum , in situ hybridization , granule cell , protein subunit , hydroxydopamine , biology , medicine , endocrinology , receptor , granule (geology) , messenger rna , central nervous system , biochemistry , dentate gyrus , paleontology , dopaminergic , dopamine , gene
Neurotoxic elimination of noradrenergic terminals by 6‐hydroxydopamine (6‐OHDA) leads to alteration of the granule cell layer formation. We have studied the developmental expression of GABA A receptor subunits in rat cerebellum after neonatal administration of 6‐OHDA during the first postnatal month of life. 6‐OHDA was injected subcutaneously. The expression of GABA A receptor subunits was studied by in situ hybridization and immunohistochemistry. The alterations were observed in the neocerebellum — the part of the cerebellum which starts development postnatally. The migration of granule cells was delayed, and the total area of the granule cell layer in the neocerebellum from 6‐OHDA‐treated rats was reduced to 22.6±5% of the corresponding area from control rats. In situ hybridization with subunit‐specific antisense oligonucleotide probes was performed for α1, α2, α3, α5, α6, β1, β2, γ1 and γ2 subunits of the GABA A receptor. In neocerebellum, 6‐OHDA treatment caused a significant reduction in the α1, α6 and γ2 subunit mRNA levels. The expression of the other subunits was not changed. It has been shown that in the postnatal cerebellum α1 and α6 subunits can be detected in granule cells only when the cells had migrated to their final destination. Our findings indicate that a noradrenergic influence may be necessary for the normal maturation and migration of cerebellar granule cells.