Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High amplitude spiking representative of seizures, accompanied by an unusual motor behavior pattern of rearing and forelimbic clonus resembling "boxing," was elicited by microinjection of the cholinergic agonist, carbachol, 4 micrograms, into the medial prefrontal cortex of the rat. A rating scale devised to score the behavior revealed a motor pattern elicited by carbachol from the medial anterior cortex which was similar to that described by Racine for electrical stimulation of the amygdala. Topographical analysis of the areas surrounding the medial anterior cortex region revealed that the motor manifestations of seizures were elicited over a wide region of the anterior cortex, with scores significantly lower at carbachol microinjection sites greater than 1 mm rostral, 2 and 3 mm caudal, and 2 mm lateral to the standard medial prefrontal cortex site. Unilateral microinjection of carbachol yielded motor seizures primarily from the contralateral forepaw, suggesting involvement of a crossed pathway. Retrograde tracing with fast blue dye, combined with immunostaining for choline acetyltransferase and NADPH-diaphorase, found that the cholinergic neurons innervating the standard microinjection site were the dorsolateral tegmental cells, as previously reported, which have been shown to also contain substance P and corticotropin releasing factor. In addition, cholinergic neurons of the nucleus basalis of Meynert region were found to innervate the standard microinjection site. These findings implicate cholinergic innervation of the rostral cortex in classical limbic seizures.
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PMID:Anatomical analysis of frontal cortex sites at which carbachol induces motor seizures in the rat. 317 34

Cryptogenic temporal lobe epilepsy develops in the absence of identified brain injuries, infections, or structural malformations, and in these cases, an unidentified pre-existing abnormality may initiate febrile seizures, hippocampal sclerosis, and epilepsy. Although a role for GABAergic dysfunction in epilepsy is intuitively obvious, no causal relationship has been established. In this study, hippocampal GABA neurons were targeted for selective elimination to determine whether a focal hippocampal GABAergic defect in an otherwise normal brain can initiate cryptogenic temporal lobe epilepsy with hippocampal sclerosis. We used Stable Substance P-saporin conjugate (SSP-saporin) to target rat hippocampal GABA neurons, which selectively and constitutively express the neurokinin-1 receptors that internalize this neurotoxin. Bilateral and longitudinally extensive intrahippocampal microinjections of SSP-saporin caused no obvious behavioral effects for several days. However, starting ~4 days postinjection, rats exhibited episodes of immobilization, abnormal flurries of "wet-dog" shakes, and brief focal motor seizures characterized by facial automatisms and forepaw clonus. These clinically subtle behaviors stopped after ~4 days. Convulsive status epilepticus did not develop, and no deaths occurred. Months later, chronically implanted rats exhibited spontaneous focal motor seizures and extreme hippocampal sclerosis. These data suggest that hippocampal GABAergic dysfunction is epileptogenic and can produce the defining features of cryptogenic temporal lobe epilepsy.
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PMID:Targeted hippocampal GABA neuron ablation by Stable Substance P-saporin causes hippocampal sclerosis and chronic epilepsy in rats. 3096 45