IMMUNOCYTOCHEMICAL LOCALIZATION OF ANGIOTENSINOGEN IN THE FETAL AND NEONATAL RAT-BRAIN

The aim of this study was to define the temporal appearance and region al distribution of angiotensinogen in the fetal and neonatal rat brain . This was done by immunocytochemical localization of angiotensinogen in brains from embryonic day 16 to postnatal day 12. Immunostaining wa s first observed on embryonic day 18, and persisted to postnatal day 2 , in the choroid plexus and ependymal cells lining the third ventricle . This initial expression of angiotensinogen at embryonic day 18 was f ollowed at postnatal day 20 by a rapid progression of angiotensinogen staining appearing in astrocytes ib the paraventricular nucleus, media l preoptic area, ventromedial and arcuate hypothalamic nuclei; these a reas showed the highest astrocyte staining intensity in the brain. Thi s was followed sequentially by staining in areas of the thalamus, midb rain, forebrain and brainstem. In general, neuroglial staining was hig her in regions proximal to the cerebral ventricles and cerebral aquedu ct. Neuronal angiotensinogen was observed al day postnatal day 0 and l ater. The most consistent immunopositive areas were in the forebrain a nd thalamus; in particular, the hippocampus, anterior and posterior ci ngulate cortex, basal and lateral amygdala, the caudate-putamen, globu s pallidus, lateral septum, medial habenular nuclei and lateral thalam ic nuclei. Most of the immunopositive cells in the hypothalamus and br ainstem were astrocytes, while those in the cortex were almost exclusi vely neurons. Staining in thalamic regions was both neuronal and neuro glial. From the intensity of staining and cell density, it was determi ned that a rapid increase in angiotensinogen occurs between embryonic day 20 and postnatal day 0, followed by further, smaller increases pos tnatally. In conclusion, this study has shown that angiotensinogen, th e protein from which angiotensin II is generated, is present in the ra t fetal brain. The timing of its appearance supports the establishment of a renin-angiotensin system by late gestation. Its predominance in fetal hypothalamic nuclei and in thalamic, cerebellar and cortical neu rons suggests major roles in perinatal fluid and electrolyte balance, in sensorimotor development and in brain muturation.