Cutamesine Overcomes REM Sleep Deprivation-Induced Memory Loss: Relationship to Sigma-1 Receptor Occupancy

Nisha Kuzhuppilly Ramakrishnan; Marianne Schepers; Gert Luurtsema; Csaba J. Nyakas; Philip H. Elsinga; Kiichi Ishiwata; Rudi A. J. O. Dierckx; Aren van Waarde

doi:10.1007/s11307-014-0808-2

Cutamesine Overcomes REM Sleep Deprivation-Induced Memory Loss: Relationship to Sigma-1 Receptor Occupancy

Nisha Kuzhuppilly Ramakrishnan, Marianne Schepers, Gert Luurtsema, Csaba J. Nyakas, Philip H. Elsinga, Kiichi Ishiwata, Rudi A. J. O. Dierckx, Aren van Waarde^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

6 Citations (Scopus)

Abstract

Rapid eye movement (REM) sleep deprivation (SD) decreases cerebral sigma-1 receptor expression and causes cognitive deficits. Sigma-1 agonists are cognitive enhancers. Here, we investigate the effect of cutamesine treatment in the REM SD model.

Sigma-1 receptor occupancy (RO) in the rat brain by cutamesine was determined using 1-[2-(3,4-dimethoxyphenethyl)]-4-(3-phenylpropyl)piperazine ([C-11]SA4503) and positron emission tomography (PET), and tissue cutamesine levels were measured by ultra performance liquid chromatography (UPLC)-MS. RO was calculated from a Cunningham-Lassen plot, based on the total distribution volume of [C-11]SA4503 determined by Logan graphical analysis. Cognitive performance was assessed using the passive avoidance (PA) test.

Cutamesine at a dose of 1.0 mg/kg reversed REM SD-induced cognitive deficit and occupied 92 % of the sigma-1 receptor population. A lower dose (0.3 mg/kg) occupied 88 % of the receptors but did not significantly improve cognition.

The anti-amnesic effect of cutamesine in this animal model may be related to longer exposure at a higher dose and/or drug binding to secondary targets.

Original language	English
Pages (from-to)	364-372
Number of pages	9
Journal	Molecular Imaging and Biology
Volume	17
Issue number	3
DOIs	https://doi.org/10.1007/s11307-014-0808-2
Publication status	Published - Jun-2015

Keywords

Sigma-1 receptor
Receptor occupancy
Cutamesine
REM sleep deprivation
Amnesia
Positron emission tomography
Passive avoidance
POSITRON-EMISSION-TOMOGRAPHY
SELECTIVE CHOLINERGIC LESION
COGNITIVE ENHANCER
RAT-BRAIN
BEHAVIORAL EVIDENCE
OBJECT RECOGNITION
INDUCED AMNESIA
MODULATING ROLE
IN-VIVO
SA4503

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Cutamesine Overcomes REM Sleep Deprivation-Induced
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@article{1efbcc7dccd74f9fbd5722a22232a76c,

title = "Cutamesine Overcomes REM Sleep Deprivation-Induced Memory Loss: Relationship to Sigma-1 Receptor Occupancy",

abstract = "Rapid eye movement (REM) sleep deprivation (SD) decreases cerebral sigma-1 receptor expression and causes cognitive deficits. Sigma-1 agonists are cognitive enhancers. Here, we investigate the effect of cutamesine treatment in the REM SD model.Sigma-1 receptor occupancy (RO) in the rat brain by cutamesine was determined using 1-[2-(3,4-dimethoxyphenethyl)]-4-(3-phenylpropyl)piperazine ([C-11]SA4503) and positron emission tomography (PET), and tissue cutamesine levels were measured by ultra performance liquid chromatography (UPLC)-MS. RO was calculated from a Cunningham-Lassen plot, based on the total distribution volume of [C-11]SA4503 determined by Logan graphical analysis. Cognitive performance was assessed using the passive avoidance (PA) test.Cutamesine at a dose of 1.0 mg/kg reversed REM SD-induced cognitive deficit and occupied 92 % of the sigma-1 receptor population. A lower dose (0.3 mg/kg) occupied 88 % of the receptors but did not significantly improve cognition.The anti-amnesic effect of cutamesine in this animal model may be related to longer exposure at a higher dose and/or drug binding to secondary targets.",

keywords = "Sigma-1 receptor, Receptor occupancy, Cutamesine, REM sleep deprivation, Amnesia, Positron emission tomography, Passive avoidance, POSITRON-EMISSION-TOMOGRAPHY, SELECTIVE CHOLINERGIC LESION, COGNITIVE ENHANCER, RAT-BRAIN, BEHAVIORAL EVIDENCE, OBJECT RECOGNITION, INDUCED AMNESIA, MODULATING ROLE, IN-VIVO, SA4503",

author = "{Kuzhuppilly Ramakrishnan}, Nisha and Marianne Schepers and Gert Luurtsema and Nyakas, {Csaba J.} and Elsinga, {Philip H.} and Kiichi Ishiwata and Dierckx, {Rudi A. J. O.} and {van Waarde}, Aren",

year = "2015",

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doi = "10.1007/s11307-014-0808-2",

language = "English",

volume = "17",

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journal = "Molecular Imaging and Biology",

issn = "1536-1632",

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Cutamesine Overcomes REM Sleep Deprivation-Induced Memory Loss : Relationship to Sigma-1 Receptor Occupancy. / Kuzhuppilly Ramakrishnan, Nisha; Schepers, Marianne ; Luurtsema, Gert; Nyakas, Csaba J.; Elsinga, Philip H.; Ishiwata, Kiichi; Dierckx, Rudi A. J. O.; van Waarde, Aren.

In: Molecular Imaging and Biology, Vol. 17, No. 3, 06.2015, p. 364-372.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Cutamesine Overcomes REM Sleep Deprivation-Induced Memory Loss

T2 - Relationship to Sigma-1 Receptor Occupancy

AU - Kuzhuppilly Ramakrishnan, Nisha

AU - Schepers, Marianne

AU - Luurtsema, Gert

AU - Nyakas, Csaba J.

AU - Elsinga, Philip H.

AU - Ishiwata, Kiichi

AU - Dierckx, Rudi A. J. O.

AU - van Waarde, Aren

PY - 2015/6

Y1 - 2015/6

N2 - Rapid eye movement (REM) sleep deprivation (SD) decreases cerebral sigma-1 receptor expression and causes cognitive deficits. Sigma-1 agonists are cognitive enhancers. Here, we investigate the effect of cutamesine treatment in the REM SD model.Sigma-1 receptor occupancy (RO) in the rat brain by cutamesine was determined using 1-[2-(3,4-dimethoxyphenethyl)]-4-(3-phenylpropyl)piperazine ([C-11]SA4503) and positron emission tomography (PET), and tissue cutamesine levels were measured by ultra performance liquid chromatography (UPLC)-MS. RO was calculated from a Cunningham-Lassen plot, based on the total distribution volume of [C-11]SA4503 determined by Logan graphical analysis. Cognitive performance was assessed using the passive avoidance (PA) test.Cutamesine at a dose of 1.0 mg/kg reversed REM SD-induced cognitive deficit and occupied 92 % of the sigma-1 receptor population. A lower dose (0.3 mg/kg) occupied 88 % of the receptors but did not significantly improve cognition.The anti-amnesic effect of cutamesine in this animal model may be related to longer exposure at a higher dose and/or drug binding to secondary targets.

AB - Rapid eye movement (REM) sleep deprivation (SD) decreases cerebral sigma-1 receptor expression and causes cognitive deficits. Sigma-1 agonists are cognitive enhancers. Here, we investigate the effect of cutamesine treatment in the REM SD model.Sigma-1 receptor occupancy (RO) in the rat brain by cutamesine was determined using 1-[2-(3,4-dimethoxyphenethyl)]-4-(3-phenylpropyl)piperazine ([C-11]SA4503) and positron emission tomography (PET), and tissue cutamesine levels were measured by ultra performance liquid chromatography (UPLC)-MS. RO was calculated from a Cunningham-Lassen plot, based on the total distribution volume of [C-11]SA4503 determined by Logan graphical analysis. Cognitive performance was assessed using the passive avoidance (PA) test.Cutamesine at a dose of 1.0 mg/kg reversed REM SD-induced cognitive deficit and occupied 92 % of the sigma-1 receptor population. A lower dose (0.3 mg/kg) occupied 88 % of the receptors but did not significantly improve cognition.The anti-amnesic effect of cutamesine in this animal model may be related to longer exposure at a higher dose and/or drug binding to secondary targets.

KW - Sigma-1 receptor

KW - Receptor occupancy

KW - Cutamesine

KW - REM sleep deprivation

KW - Amnesia

KW - Positron emission tomography

KW - Passive avoidance

KW - POSITRON-EMISSION-TOMOGRAPHY

KW - SELECTIVE CHOLINERGIC LESION

KW - COGNITIVE ENHANCER

KW - RAT-BRAIN

KW - BEHAVIORAL EVIDENCE

KW - OBJECT RECOGNITION

KW - INDUCED AMNESIA

KW - MODULATING ROLE

KW - IN-VIVO

KW - SA4503

U2 - 10.1007/s11307-014-0808-2

DO - 10.1007/s11307-014-0808-2

M3 - Article

C2 - 25449772

VL - 17

SP - 364

EP - 372

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

SN - 1536-1632

IS - 3

ER -