The effects of thyrotropin-releasing hormone and scopolamine in Alzheimer's disease and normal volunteers

Molchan, Susan E.; Mellow, Alan M.; Hill, James L.; Weingartner, Herbert; Martínez, Rick A.; Vitiello, Benedetto; Sunderland, Trey

doi:10.1177/026988119200600404

Cited by 19 publications

(6 citation statements)

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“…A similar facilitation has also been seen in patients with Alzheimer's disease following TRH treatment (Mellow et al 1989(Mellow et al ,1993Molchan et al 1992) and in volunteer subjects treated with scopolamine (Molchan et al 1990(Molchan et al ,1992. However, the effectiveness of systemic neuropeptidergic treat-…”

mentioning

confidence: 54%

Further Evidence for a Dissociation Between Different Forms of Mnemonic Expressions in a Mouse Model of Age-related Cognitive Decline: Effects of Tacrine and S 17092, a Novel Prolyl Endopeptidase Inhibitor

Marighetto¹,

Touzani²,

Etchamendy³

et al. 2000

Learn. Mem.

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It has been demonstrated previously on the radial maze that the emergence of an age-related mnemonic impairment is critically dependent on the form which the discrimination problems took. Hence, when the arms were presented one by one (i.e., successive go-no-go discrimination), both adult and aged mice learned to distinguish between positive (baited) and negative (unbaited) arms readily, as evidenced by their increased readiness to enter positive relative to negative arms (i.e., by a differential in arm-entry latencies). A selective impairment in the aged mice was seen when these arms were presented subsequently as pairs, such that the mice were confronted with an explicit choice (i.e., simultaneous 2-choice discrimination). When discriminative performance was measured by the differential run speed between positive and negative arms, aged mice were also impaired. This was particularly pronounced in the 2-choice discrimination condition. We examined the effects of tacrine (3mg/kg, subcutaneously) or S 17092 (10mg/kg, orally) in aged mice on the three behavioral indices of this 2-stage spatial discrimination paradigm. The results indicated that: (1) Tacrine, but not S 17092, enhanced the acquisition of go-no-go discrimination as reflected in arm-entry latencies; (2) both drugs improved choice accuracy in simultaneous discrimination, although the effect of tacrine was less striking and, in particular, far from statistical significance in the very first 2-choice responses; and (3) neither drugs significantly affected run-speed performance. We conclude further that the specific patterns of drug effects on the three indices of discriminative performance might suggest that each index is associated with a distinct form of mnemonic expression relying on separate neural systems.In humans, declarative/explicit memory appears to be more vulnerable to deterioration in senescence than procedural/ implicit memory (Poon 1985;Gabrieli 1996;Schugens et al. 1997). One cardinal characteristic of declarative memory is its flexibility as exemplified by its capacity to support inferential use of memories in novel situations (Cohen 1984). Using a two-stage paradigm of discrimination learning, Marighetto et al. (1999) have previously demonstrated that aged mice displayed impaired inferential abilities when they were required to make an explicit choice between two eventualities that were only encountered before separately, but never conjointly. In Stage 1, the mice learned to discriminate between the valence of three baited (positive) and three unbaited (negative) arms in a radial maze with each of the arms presented one at a time, i.e., successive go-no-go discrimination. Successful discrimination was indicated by the animals' increased readiness to enter positive arms relative to negative ones. In Stage 2, the animals were confronted with an explicit choice between one positive arm and one negative arm they had learned to discriminate previously. Aged mice, but not young ones, were unable to translate their preference for the positive ...

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confidence: 54%

Further Evidence for a Dissociation Between Different Forms of Mnemonic Expressions in a Mouse Model of Age-related Cognitive Decline: Effects of Tacrine and S 17092, a Novel Prolyl Endopeptidase Inhibitor

Marighetto¹,

Touzani²,

Etchamendy³

et al. 2000

Learn. Mem.

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“…This suggestion is further supported by evidence for a beneficial effect on mnemonic performance of SP in aged rats (15). A similar facilitation has also been seen in patients with Alzheimer's disease following TRH treatment (32,33,34) and in volunteer subjects treated with scopolamine (34,35). However, the effectiveness of systemic neuropeptidergic treatments is generally viewed with scepticism because of the relative impermeability of the blood brain barrier for these peptides.…”

Section: Introductionmentioning

confidence: 71%

S 17092: A Prolyl Endopeptidase Inhibitor as a Potential Therapeutic Drug for Memory Impairment. Preclinical and Clinical Studies

et al. 2002

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Any treatment that could positively modulate central neuropeptides levels would provide a promising therapeutic approach to the treatment of cognitive deficits associated with aging and/or neurodegenerative diseases. Therefore, based on the activity in rodents, S 17092 (2S,3aS,7aS)-1{[(R,R)-2-phenylcyclopropyl]carbonyl}-2-[(thiazolidin-3-yl)carbonyl]octahydro-1H-indole) has been selected as a potent inhibitor of cerebral prolylendopeptidase (PEP). By retarding the degradation of neuroactive peptides, S 17092 was successfully used in a variety of memory tasks. These tasks explored short-term, longterm, reference and working memory in aged mice, as well as in rodents and monkeys with chemically induced amnesia or spontaneous memory deficits. S 17092 has also been safely administered to humans, and showed a clear peripheral expression of its mechanism of action through its inhibitory effect upon PEP activity in plasma. S 17092 exhibited central effects, as evidenced by EEG recording in healthy volunteers, and could improve a delayed verbal memory task. Collectively, the preclinical and clinical effects of S 17092 have suggested a promising role for this compound as an agent for the treatment of cognitive disorders associated with cerebral aging.

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“…Findings of previous studies have shown that a similar symptom was induced by SCOP (24), which is known as a cholinergic receptor antagonist. SCOP-treated animals have been widely used to estimate memory impairment and screening of potential cognition-enhancing agents.…”

Section: Discussionmentioning

confidence: 89%

Bushen-Yizhi formula ameliorates cognition deficits and attenuates oxidative stress-related neuronal apoptosis in scopolamine-induced senescence in mice

Hou

Wu²,

Zhang

et al. 2014

International Journal of Molecular Medicine

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Bushen-Yizhi formula (BSYZ), a traditional Chinese medicine formula consisting of six herbs has been reported to possess a neuroprotective effect. The present study aimed to investigate the effects of BSYZ on learning and memory abilities, as well as oxidative stress and neuronal apoptosis in the hippocampus of scopolamine (SCOP)-induced senescence in mice, in order to reveal whether BSYZ is a potential therapeutic agent for Alzheimer’s disease (AD). A high-performance liquid chromatography (HPLC) fingerprint was applied to provide a chemical profile of BSYZ. Extracts of BSYZ were orally administered to mice with SCOP-induced memory impairment for two weeks. The learning and memory abilities were determined by the Morris water maze test. The oxidant stress-related indices, such as activity of superoxide dismutase (SOD) and levels of glutathione (GSH) and malondialdehyde (MDA) were examined in hippocampus of SCOP-treated mice. The cell death ratio was assessed by TUNEL staining, while apoptotic-related proteins including Bcl-2 and Bax were determined by immunofluorescent staining and western blot analysis. Caspase-3 was determined by western blot analysis. Consequently, a chromatographic condition, which was conducted at 35°C with a flow rate of 0.8 ml/min on the Gemini C18 column with mobile phase of acetonitrile and water-phosphoric acid (100:0.1, v/v), was established to yield common fingerprint chromatography under 203 nm with a similarity index of 0.986 within 10 batches of BSYZ samples. BSYZ at a dose of 2.92 g/kg significantly improved the cognitive ability, restored the abnormal activity of SOD and increased the levels of MDA and GSH induced by SCOP. Moreover, the neural apoptosis in the hippocampus of SCOP-treated mice was reversed by BSYZ by regulating the expression of Bcl-2, Bax and caspase-3. The results demonstrated that BSYZ had neuroprotective effects in SCOP-induced senescence in mice by ameliorating oxidative stress and neuronal apoptosis in the brain, supporting its potential in AD treatment.

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The effects of thyrotropin-releasing hormone and scopolamine in Alzheimer's disease and normal volunteers

Cited by 19 publications

References 64 publications

Further Evidence for a Dissociation Between Different Forms of Mnemonic Expressions in a Mouse Model of Age-related Cognitive Decline: Effects of Tacrine and S 17092, a Novel Prolyl Endopeptidase Inhibitor

Further Evidence for a Dissociation Between Different Forms of Mnemonic Expressions in a Mouse Model of Age-related Cognitive Decline: Effects of Tacrine and S 17092, a Novel Prolyl Endopeptidase Inhibitor

S 17092: A Prolyl Endopeptidase Inhibitor as a Potential Therapeutic Drug for Memory Impairment. Preclinical and Clinical Studies

Bushen-Yizhi formula ameliorates cognition deficits and attenuates oxidative stress-related neuronal apoptosis in scopolamine-induced senescence in mice

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