Neuropeptide substance P improves water maze performance in aged rats

Hasenöhrl, Rüdiger U.; Huston, Joseph P.; Schuurman, T.

doi:10.1007/bf02253712

Cited by 36 publications

(16 citation statements)

References 24 publications

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“…However, it is possible that the memory-facilitating effect of SP is not solely modulated by NK1-Rs on cholinergic neurons, but also by NK3-Rs, because SP, although with highest affinity to NK1-Rs, can also bind to NK3-Rs (9,29). Our current finding of memory facilitation via NK3-R activation by senktide and the consequential increase of ACh release might also account for previously described memory-promoting effects of SP in aged animals (26).…”

Section: Discussionsupporting

confidence: 72%

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Neurokinin3 receptor as a target to predict and improve learning and memory in the aged organism

Silva

Lenz

Rotter

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Impaired learning and memory performance is often found in aging as an early sign of dementia. It is associated with neuronal loss and reduced functioning of cholinergic networks. Here we present evidence that the neurokinin3 receptors (NK3-R) and their influence on acetylcholine (ACh) release may represent a crucial mechanism that underlies age-related deficits in learning and memory. Repeated pharmacological stimulation of NK3-R in aged rats was found to improve learning in the water maze and in object-place recognition. This treatment also enhanced in vivo acetylcholinergic activity in the frontal cortex, hippocampus, and amygdala but reduced NK3-R mRNA expression in the hippocampus. Furthermore, NK3-R agonism incurred a significantly higher increase in ACh levels in aged animals that showed superior learning than in those that were most deficient in learning. Our findings suggest that the induced activation of ACh, rather than basal ACh activity, is associated with superior learning in the aged. To test whether natural variation in NK3-R function also determines learning and memory performance in aged humans, we investigated 209 elderly patients with cognitive impairments. We found that of the 15 analyzed single single-nucleotide ploymorphism (SNPs) of the NK3-R-coding gene, TACR3, the rs2765 SNP predicted the degree of impairment of learning and memory in these patients. This relationship could be partially explained by a reduced right hippocampus volume in a subsample of 111 tested dementia patients. These data indicate the NK3-R as an important target to predict and improve learning and memory performance in the aged organism. senktide | in vivo microdialysis H umans exhibit a decline in cognitive capacity with age, which may progressively lead to dementia (1). Age-dependent morphological and physiological changes within the cholinergic system of the brain have been described as a major mechanism underlying impairments of learning and memory (2, 3). Numerous studies in aged rats have revealed that a degeneration of cholinergic neurons in the basal forebrain is associated with learning and >memory deficits (4). Likewise, the consistent correlations found between cholinergic degeneration and cognitive impairments indicate a high correspondence between acetylcholinergic activity and the magnitude of cognitive decline (4-6). This relationship has also been shown in patients with Alzheimer's disease (7,8).The neuropeptide neurokinins (NKs) substance P, neurokinin A, neurokinin B (NK-B), neuropeptide K, neuropeptide γ, and hemokinin 1 bind to the three known NK-receptors (NK3-R) (NK1-, NK2-, and NK3-R) with different degrees of affinity, whereby NK-B is the preferred ligand to NK3-R (9). NK3-Rs are widespread in the brain, including areas that are implicated in processes governing learning and memory such as the hippocampus, frontal cortex (FC), and medial septum (10, 11). There is a close interaction between NK3-R and the cholinergic system. NK3-R are localized on cholinacetyltransferase-containing neurons in ...

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Section: Discussionsupporting

confidence: 72%

“…Aged humans and animals show considerable individual differences in performance in cognitive tasks (21,22,26,27). Ageassociated differences in sensitivity to NK3-R agonism most likely reflect differences in cholinergic degeneration (35).…”

Section: Discussionmentioning

confidence: 99%

Neurokinin3 receptor as a target to predict and improve learning and memory in the aged organism

Silva

Lenz

Rotter

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…For example, deficiencies in substance P and vasopressin have been reported in postmortem studies of cerebral tissue derived from patients with neurodegenerative diseases (Ferrier et al 1983;Rossor et al 1986;Beal and Mazurek 1987;Husain and Nemeroff 1990). Hence, peptidergic alterations might play a significant role in age-related cognitive decline.This suggestion is further supported by evidence for a beneficial effect on mnemonic performance following substance P treatment in aged rats (Hasenöhrl et al 1990). 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.…”

mentioning

confidence: 60%

“…This suggestion is further supported by evidence for a beneficial effect on mnemonic performance following substance P treatment in aged rats (Hasenöhrl et al 1990). 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.…”

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confidence: 60%

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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“…Administration of SP has also been reported to improve passive and active avoidance performance (Pelleymounter et al 1986;Schlesinger et al 1983) and ICV administration of NKA enhances T-maze learning (Flood et al 1990). Systemic administration of SP has also been demonstrated to counteract age-related learning deficits (Hasenohrl et al 1990(Hasenohrl et al , 1994. In addition, SPfragment studies have demonstrated that the effects of SP seem to be encoded by different SP-sequences with the Nterminal SP1-7 enhancing memory, while the C-terminal heptapeptide and hexapeptide sequences of SP appear to mediate its reinforcing properties (Huston and Hasenohrl 1995).…”

Section: Discussionmentioning

confidence: 98%

Disruption of the neurokinin-3 receptor (NK3) in mice leads to cognitive deficits

et al. 2007

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Neuropeptide substance P improves water maze performance in aged rats

Cited by 36 publications

References 24 publications

Neurokinin3 receptor as a target to predict and improve learning and memory in the aged organism

Neurokinin3 receptor as a target to predict and improve learning and memory in the aged organism

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

Disruption of the neurokinin-3 receptor (NK3) in mice leads to cognitive deficits

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