(−)-P7C3-S243 Protects a Rat Model of Alzheimer’s Disease From Neuropsychiatric Deficits and Neurodegeneration Without Altering Amyloid Deposition or Reactive Glia

Jaymie R Voorhees; Matthew T Remy; Coral J Cintrón-Pérez; Eli El Rassi; Michael Z Khan; Laura M Dutca; Terry C Yin; Latisha N McDaniel; Noelle S Williams; Daniel J Brat; Andrew A Pieper

doi:10.1016/j.biopsych.2017.10.023

Back

(−)-P7C3-S243 Protects a Rat Model of Alzheimer’s Disease From Neuropsychiatric Deficits and Neurodegeneration Without Altering Amyloid Deposition or Reactive Glia

Journal article

Open access

Peer reviewed

(−)-P7C3-S243 Protects a Rat Model of Alzheimer’s Disease From Neuropsychiatric Deficits and Neurodegeneration Without Altering Amyloid Deposition or Reactive Glia

Jaymie R Voorhees, Matthew T Remy, Coral J Cintrón-Pérez, Eli El Rassi, Michael Z Khan, Laura M Dutca, Terry C Yin, Latisha N McDaniel, Noelle S Williams, Daniel J Brat, …

Biological psychiatry (1969), Vol.84(7), pp.488-498

10/01/2018

DOI: 10.1016/j.biopsych.2017.10.023

PMCID: PMC6415524

PMID: 29246437

Files and links (1)

url

https://doi.org/10.1016/j.biopsych.2017.10.023View

Published (Version of record) Open Access

Abstract

In addition to cognitive deficits, Alzheimer’s disease (AD) is associated with other neuropsychiatric symptoms, including severe depression. Indeed, depression often precedes cognitive deficits in patients with AD. Unfortunately, the field has seen only minimal therapeutic advances, underscoring the critical need for new treatments. P7C3 aminopropyl carbazoles promote neuronal survival by enhancing nicotinamide adenine dinucleotide flux in injured neurons. Neuroprotection with P7C3 compounds has been demonstrated in preclinical models of neurodegeneration by virtue of promoting neuronal survival independently of early disease-specific pathology, resulting in protection from cognitive deficits and depressive-like behavior. We hypothesize that P7C3 compounds might be uniquely applicable to patients with AD, given the comorbid presentation of depression and cognitive deficits. Aging male and female wild-type and TgF344-AD rats, a well-characterized preclinical AD model, were administered (−)-P7C3-S243 daily for 9 and 18 months, beginning at 6 months of age. Behavioral phenotypes related to cognition and depression were assessed at 15 and 24 months, and brain pathology and biochemistry were assessed at 24 months. (−)-P7C3-S243 safely protected aging male and female wild-type and TgF344-AD rats from cognitive deficits and depressive-like behavior. Depressive-like behavior occurred earlier than cognitive deficits in TgF344-AD rats, consistent with AD in many patients. Treatment with (−)-P7C3-S243 blocked neurodegeneration in TgF344-AD rats, without altering amyloid deposition or indicators of neuroinflammation. Neuronal cell death–specific treatment approaches, such as P7C3 compounds, may represent a new treatment approach for patients experiencing the combination of cognitive deficits and depression associated with AD.

Neuroprotection

P7C3

Alzheimer’s disease

Neurodegeneration

Depression

Neurogenesis

TgF344-AD

Details

Title: Subtitle: (−)-P7C3-S243 Protects a Rat Model of Alzheimer’s Disease From Neuropsychiatric Deficits and Neurodegeneration Without Altering Amyloid Deposition or Reactive Glia
Creators: Jaymie R Voorhees - Department of Psychiatry, Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, Iowa
Matthew T Remy - Department of Psychiatry, Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, Iowa
Coral J Cintrón-Pérez - Department of Psychiatry, Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, Iowa
Eli El Rassi - Department of Psychiatry, Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, Iowa
Michael Z Khan - Department of Psychiatry, Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, Iowa
Laura M Dutca - Department of Ophthalmology and Visual Sciences, Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, Iowa
Terry C Yin - Department of Psychiatry, Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, Iowa
Latisha N McDaniel - Department of Psychiatry, Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, Iowa
Noelle S Williams - Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas
Daniel J Brat - Division of Laboratory Medicine, Department of Pathology, Emory University, Atlanta, Georgia
Andrew A Pieper - Department of Psychiatry, Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, Iowa
Resource Type: Journal article
Publication Details: Biological psychiatry (1969), Vol.84(7), pp.488-498
DOI: 10.1016/j.biopsych.2017.10.023
PMID: 29246437
PMCID: PMC6415524
NLM abbreviation: Biol Psychiatry
ISSN: 0006-3223
eISSN: 1873-2402
Publisher: Elsevier Inc
Language: English
Date published: 10/01/2018
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Otolaryngology; Ophthalmology and Visual Sciences
Record Identifier: 9984071795202771

Metrics

27 Record Views

60 Times Cited - Web of Science