ON THE PLASTICITY OF THE CEREBELLAR RENIN-ANGIOTENSIN SYSTEM - LOCALIZATION OF COMPONENTS AND EFFECTS OF MECHANICAL PERTURBATION

This study focuses on the renin-angiotensin system (RAS) in the cerebe llar cortex and changes within this system after mechanically induced cerebellar injury. Using radioactive and non-radioactive in situ hybri dization and immunocytochemistry angiotensinogen mRNA, angiotensinogen , angiotensin II and, for the first time, N-terminal angiotensin fragm ent (1-7) immunoreactivities, respectively, were demonstrated in the r at cerebellum. Angiotensinogen mRNA and angiotensinogen immunoreactivi ty (IR) were both present in glial cell populations of all layers, esp ecially in the Purkinje and granular cell layers and within the cerebe llar nuclei. Angiotensin II IR was demonstrated in glial cell populati ons in all layers using a monoclonal angiotensin II antibody, while wi th a polyclonal angiotensin II antiserum (Denise) some Purkinje cell b odies were labelled. After lesioning the cerebellar cortex mechanicall y by an injection cannula a strong increase in angiotensinogen gene ex pression as well as in angiotensin II and angiotensin (1-7) immunoreac tivities were observed in the glial cell populations. Furthermore, put ative Bergmann glial processes, as indicated from the morphological ap pearance became strongly angiotensin II and angiotensinogen immunoreac tive in the region close to the mechanically induced lesion. It could inter alia be demonstrated for the first time using confocal laser mic roscopy of ANG II IR and GFAP IR that ANG II in vivo in the intact cer ebellar cortex is present in astroglial processes in the molecular lay er and presumably secreted into the extracellular space in form of sma ll spheric bodies and/or taken up by other cell types. In contrast, th e N-terminal fragment angiotensin (1-7) IR was restricted to the glial cell populations and appeared only after the lesion event. Thus, it i s suggested that the cerebellar RAS shows marked changes in response t o mechanically induced lesions. The expression of angiotensinogen as w ell as the production of angiotensinogen IR and angiotensin II like IR is even after mechanical lesion restricted to astrocytes, i.e., cereb ellar astrocytes and putative Bergmann glial cells, and in case of imm unoreactivities it spreads to the radially oriented Bergmann glial pro cesses in the molecular layer.