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Electroconvulsive shock-induced amnesia. Action of neuropeptides
$4-B2-1-03 IMMUNOCYTOCHEMICAL STUDIES ON B-AMYLOIDOGENESlS Takeshi lwatsubo Department of Neuropathology and Neuroscience, Faculty of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan To learn about the pathomechanism of B-amyloidogenesis and especially the carboxyl-terminal extent of amyloid B protein (AB) deposits in Alzheimer's disease (AD) brains, we immunocytochemically probed senile plaques (SPs) with end-specific AB monoclonals that s p e c i f i c a l l y react with the carboxyl terminus of ABI-40 (AB40) and AB42(43) respectively. In the cerebral cortices of sporadic AD, a l l SPs were AB42(43)-positive, one t h i r d of which, on average, were also AB40-positive. Amyloid cores of typical SPs were frequently p o s i t i v e for AB40. Two cases of f a m i l i a l AD with APP717 (Val to l l e ) mutation showed marked predominance of AB42(43)-positive AB40-negative SPs. Diffuse plaques (DPs), that are considered to represent the e a r l i e s t stage of AB deposition, in the cerebral cortex of Down's syndrome (DS), non-demented individuals as well as those in the cerebellum and striatum of AD were e x c l u s i v e l y p o s i t i v e for AB42(43) and negative for AB40. To f u r t h e r c l a r i f y the temporal r e l a t i o n s h i p of the deposition of AB42(43) and AB40 in SPs, 15 DS brains ranging in age from 31 to 64 years were s i m i l a r l y studied. Among 7 cases of 30's and 40's, 4 cases showed almost e x c l u s i v e l y AB42(43)-positive, AB40-negative DPs and others contained some AB40-positive SPs in addition to DPs. Eight cases in 50's and 60's showed frequent typical SPs in addition to DPs or immature SPs and the proportion of AB40positive SPs was increased. These data suggest that ( i ) AB42(43) is the only molecular species that i n i t i a l l y deposits as SP amyloid, ( i i ) AB40 appears l a t e r in a subset of SPs, presumably by p r o t e o l y t i c processing and ( i i i ) the APP717 mutation enhances the deposition of AB42(43).
$4-B2-1-04
ELECTROCONVULSIVE SHOCK-INDUCEDAMNESIA. ACTION OF NEUROPEPTIDES G. Telegdy Institute of Pathophysiology A.Szent-Gy~rgyi Medical University, Szeged, Hungary In passive avoidance learning, which is based on the one-trial passive avoidance paradigm, electroconvulsive shock will cause amnesia when it is applied immediatelly after the learning trial. Number of neuropeptides, tested in our Department, could attenuate or block the electroconvulsion-induced amnesla. Such peptides are as follows: Cholecystokinin-octapeptide in sulfated and non sulfated forms as well as fragments, somatostatin and some analogues, glutaurin, MIF and number of analogues, pipecolic acid, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), bombesin. In order to explore the possible involvement of neurotransmitters in the antiamnesic properties of some of these neuropeptides, the animals were pretreated with transmitter receptor blockers with doses which themselves did not modify the learning itself or the smnesic action of electroconvulsion. The antismnesic action of somatostatin could be blocked by alpha-adrenergic (phenoxybenzamine 2.0 mg/kg i.p.) and beta-adrenergic (propranolol i0 mg/kg i.p.) however dopaminergic receptor blocker (haloperidol i0 ug/kg i.p. ) and cholinergic receptor blocker (atropine 2 mg/kg i.p.) was ineffective. The anticonvulsive action of ANP was prevented by haloperidol, propanolol and atropine. Phenoxobenzamine, bicuculline (i mg/kg i.p.) methysergide (5 mg/kg i.p.) and naloxone were ineffective. BNP action on a~mesia was blocked by alpha-, beta-adrenergic and cholinergic receptor (atropine 2.0 mg/kg i.p.) blockers. Other receptor blockers bad no action. In the antism~nesic action of bombesin only haloperidol was affective in blocking the action. In the CGRP caused antis~mesic action alpha-, beta-adrenergic, cholinergic and opiates (naloxone 0.3 mg/kg i.p.) are involved. The results showed that in the antiamnesic action of different neuropeptides, although their action is similar, in the organization of the actions different neurotransmitters are involved.
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$4-B2-1-04
ELECTROCONVULSIVE SHOCK-INDUCEDAMNESIA. ACTION OF NEUROPEPTIDES G. Telegdy Institute of Pathophysiology A.Szent-Gy~rgyi Medical University, Szeged, Hungary In passive avoidance learning, which is based on the one-trial passive avoidance paradigm, electroconvulsive shock will cause amnesia when it is applied immediatelly after the learning trial. Number of neuropeptides, tested in our Department, could attenuate or block the electroconvulsion-induced amnesla. Such peptides are as follows: Cholecystokinin-octapeptide in sulfated and non sulfated forms as well as fragments, somatostatin and some analogues, glutaurin, MIF and number of analogues, pipecolic acid, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), bombesin. In order to explore the possible involvement of neurotransmitters in the antiamnesic properties of some of these neuropeptides, the animals were pretreated with transmitter receptor blockers with doses which themselves did not modify the learning itself or the smnesic action of electroconvulsion. The antismnesic action of somatostatin could be blocked by alpha-adrenergic (phenoxybenzamine 2.0 mg/kg i.p.) and beta-adrenergic (propranolol i0 mg/kg i.p.) however dopaminergic receptor blocker (haloperidol i0 ug/kg i.p. ) and cholinergic receptor blocker (atropine 2 mg/kg i.p.) was ineffective. The anticonvulsive action of ANP was prevented by haloperidol, propanolol and atropine. Phenoxobenzamine, bicuculline (i mg/kg i.p.) methysergide (5 mg/kg i.p.) and naloxone were ineffective. BNP action on a~mesia was blocked by alpha-, beta-adrenergic and cholinergic receptor (atropine 2.0 mg/kg i.p.) blockers. Other receptor blockers bad no action. In the antism~nesic action of bombesin only haloperidol was affective in blocking the action. In the CGRP caused antis~mesic action alpha-, beta-adrenergic, cholinergic and opiates (naloxone 0.3 mg/kg i.p.) are involved. The results showed that in the antiamnesic action of different neuropeptides, although their action is similar, in the organization of the actions different neurotransmitters are involved.
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