Paradoxical increase in striatal neuropeptide gene expression following ischemic lesions of the cerebral cortex.
Ischemic lesions of the cerebral cortex occur frequently in humans as a result of stroke. One major consequence of the death of cortical neurons is the loss of excitatory cortical projections to subcortical regions. Little is known, however, about the transsynaptic effect of such lesions on neurotransmitter expression in subcortical structures. We have examined the effects of ischemic cortical lesions on the peptidergic neurotransmitters enkephalin and tachykinins in the striatum, a brain region massively innervated by glutamatergic cortical inputs. The levels of enkephalin and tachykinin mRNAs increased in the striatum of adult rats after thermocoagulation of pial vessels. The effects were more pronounced in the striatal region most heavily innervated by the lesioned cortex but were also observed in other striatal regions and on the contralateral side. Increased gene expression was accompanied by increased immunoreactivity for the two peptides. Elevated levels of enkephalin mRNA were observed up to 3 months after surgery in the ipsilateral striatum. Whereas results of previous studies of acute cortical ablations suggested that excitatory corticostriatal neurons were necessary to maintain normal peptide levels in striatal efferent neurons, the present data indicate that lesions of the same corticostriatal neurons secondary to local ischemia result in a paradoxical transsynaptic activation of neuropeptide synthesis in subcortical structures. This effect may play a role in the functional consequences of cortical strokes and progressive cortical atrophy in humans and may have critical bearing for their treatment and prognosis.
Salin
P
P
Department of Pharmacology, University of Pennsylvania, Philadelphia 19104.
Chesselet
M F
MF
D000818:Animals; D002545:Brain Ischemia / Q000235:genetics*; D003342:Corpus Striatum / Q000502:physiology*; D004745:Enkephalins / Q000235:genetics*; D015870:Gene Expression; D017403:In Situ Hybridization; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015320:Tachykinins / Q000235:genetics*
D004745:Enkephalins; D012333:RNA, Messenger; D015320:Tachykinins