Lesions of the dopaminergic nigrostriatal pathway alter preprosomatostatin messenger RNA levels in the striatum, the entopeduncular nucleus and the lateral hypothalamus of the rat.
The distribution and level of labeling for the messenger RNA encoding preprosomatostatin was studied in the striatum and entopeduncular nucleus of rats with and without a selective destruction of the dopaminergic nigrostriatal pathway. 6-Hydroxydopamine was injected unilaterally in the substantia nigra and the animals were killed 2 or 3 weeks after the lesion. Preprosomatostatin messenger RNA was visualized with a 35S-labeled RNA or DNA probe in frontal cryostat-cut sections by in situ hybridization histochemistry. The number of labeled cells as well as the intensity of labeling overlying each cell were measured on radioautograms developed before saturation of the emulsion. In rats with a 6-hydroxydopamine lesion, the number of labeled cells and the intensity of labeling over each cell were decreased in the striatum ipsilateral to the lesion compared to the contralateral side and to both striata of control rats. In the same sections, the number of cells in the cerebral cortex was lower in the ipsilateral side of the lesion but the difference was only significant in the frontoparietal cortex. In contrast, a massive increase (+300%) in the number of labeled cells and in the intensity of labeling per cell was observed in the entopeduncular nucleus and the adjacent lateral hypothalamus on the side ipsilateral to the lesion when compared to the contralateral side and to control rats. The results suggest that dopamine exerts opposite effects on somatostatin gene expression in neurons of the striatum and the entopeduncular nucleus/lateral hypothalamus, effects which are likely to be of importance for the control of basal ganglia output activity. In addition, the dramatic changes observed in the somatostatinergic neurons of the lateral hypothalamus, an area involved in the control of food and water intake, may be related to some aspects of the symptomatology of Parkinson's disease.
Department of Pharmacology, University of Pennsylvania, Philadelphia 19104.
J J
JJ
Soghomonian
M F
MF
Chesselet
D000818:Animals; D001345:Autoradiography; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000378:metabolism* / Q000502:physiology*; D015342:DNA Probes; D004298:Dopamine / Q000502:physiology*; D007026:Hypothalamic Area, Lateral / Q000378:metabolism*; D008297:Male; D008636:Mesencephalon / Q000033:anatomy & histology / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology*; D009693:Nucleic Acid Hybridization; D011498:Protein Precursors / Q000096:biosynthesis*; D015347:RNA Probes; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000096:biosynthesis*; D013238:Stereotaxic Techniques; D013378:Substantia Nigra / Q000033:anatomy & histology / Q000502:physiology*; D013462:Sulfur Radioisotopes
D015342:DNA Probes; D011498:Protein Precursors; D015347:RNA Probes; D012333:RNA, Messenger; D013462:Sulfur Radioisotopes; D013004:Somatostatin; D004298:Dopamine