Anatomical localization and regulation of somatostatin gene expression in the basal ganglia and its clinical implications.
The distribution of somatostatin in both the human and rat brain suggests that it is involved in numerous functions, including endocrine regulation, cognition and memory, autonomic regulation and motor activity. We have examined the regulation of somatostatin mRNA in the striatum, a brain region involved in motor and cognitive behaviour. Somatostatin and its mRNA are expressed in this region in interneurons which are resistant to ischaemia, excitotoxicity and Huntington's disease, possibly because they express high levels of superoxide dismutase. Striatal somatostatin mRNA is increased by stimulation of NMDA (N-methyl-D-aspartate) receptors. Ischaemia-induced cortical lesions also increase somatostatin gene expression in the striatum. In contrast, the levels of striatal somatostatin mRNA decrease after treatment with haloperidol, an antipsychotic agent that produces extrapyramidal symptoms, but not clozapine, which does not. Further evidence for a role for striatal somatostatin in extrapyramidal symptoms includes the observation that somatostatin mRNA levels decrease in the striatum after lesions are made in the dopaminergic pathway, a feature of Parkinson's disease. The largest change in somatostatin gene expression after dopaminergic lesions is the increase in somatostatin mRNA level sin neurons of the internal pallidum and lateral hypothalamus projecting to the lateral habenula. The results suggest that changes in brain somatostatin gene expression occur in pathological conditions and may be related to their symptoms.
Chesselet
M F
MF
Department of Pharmacology, University of Pennsylvania, School of Medicine, Philadelphia 19104-6084, USA.
Soghomonian
J J
JJ
Salin
P
P
D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D013004:Somatostatin