title: On the plasticity of the cerebellar renin-angiotensin system: localization of components and effects of mechanical perturbation.
abstract: This study focuses on the renin-angiotensin system (RAS) in the cerebellar cortex and changes within this system after mechanically induced cerebellar injury. Using radioactive and non-radioactive in situ hybridization and immunocytochemistry angiotensinogen mRNA, angiotensinogen, angiotensin II and, for the first time, N-terminal angiotensin fragment (1-7) immunoreactivities, respectively, were demonstrated in the rat cerebellum. Angiotensinogen mRNA and angiotensinogen immunoreactivity (IR) were both present in glial cell populations of all layers, especially in the Purkinje and granular cell layers and within the cerebellar nuclei. Angiotensin II IR was demonstrated in glial cell populations in all layers using a monoclonal angiotensin II antibody, while with a polyclonal angiotensin II antiserum (Denise) some Purkinje cell bodies were labelled. After lesioning the cerebellar cortex mechanically by an injection cannula a strong increase in angiotensinogen gene expression as well as in angiotensin II and angiotensin (1-7) immunoreactivities were observed in the glial cell populations. Furthermore, putative Bergmann glial processes, as indicated from the morphological appearance became strongly angiotensin II and angiotensinogen immunoreactive in the region close to the mechanically induced lesion. It could inter alia be demonstrated for the first time using confocal laser microscopy of ANG II IR and GFAP IR that ANG II in vivo in the intact cerebellar cortex is present in astroglial processes in the molecular layer and presumably secreted into the extracellular space in form of small spheric bodies and/or taken up by other cell types. In contrast, the N-terminal fragment angiotensin (1-7) IR was restricted to the glial cell populations and appeared only after the lesion event. Thus, it is suggested that the cerebellar RAS shows marked changes in response to mechanically induced lesions. The expression of angiotensinogen as well as the production of angiotensinogen IR and angiotensin II like IR is even after mechanical lesion restricted to astrocytes, i.e., cerebellar astrocytes and putative Bergmann glial cells, and in case of immunoreactivities it spreads to the radially oriented Bergmann glial processes in the molecular layer.
authors.affiliation: Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Lippoldt
authors.forename: B
authors.initials: B
authors.lastname: Bunnemann
authors.forename: A
authors.initials: A
authors.lastname: Ueki
authors.forename: L
authors.initials: L
authors.lastname: Rosén
authors.forename: A
authors.initials: A
authors.lastname: Cintra
authors.forename: U
authors.initials: U
authors.lastname: Hasselrot
authors.forename: R
authors.initials: R
authors.lastname: Metzger
authors.forename: U
authors.initials: U
authors.lastname: Hilgenfeldt
authors.forename: B
authors.initials: B
authors.lastname: Brosnihan
authors.forename: D
authors.initials: D
authors.lastname: Ganten
mesh_terms: D000803:Angiotensin I / Q000032:analysis; D000804:Angiotensin II / Q000032:analysis; D000808:Angiotensinogen / Q000032:analysis; D000818:Animals; D002531:Cerebellum / Q000737:chemistry* / Q000293:injuries* / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000737:chemistry; D009473:Neuronal Plasticity; D010446:Peptide Fragments / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System
chemical_list: D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; D012333:RNA, Messenger; D000808:Angiotensinogen; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)