All-trans retinoic acid (ATRA) prevents lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment in aged rats

Nassima Behairi; Mourad Belkhelfa; Hayet Rafa; Moussa Labsi; Nahla Deghbar; Nora Bouzid; Hamida Mesbah-Amroun; Chafia Touil-Boukoffa

doi:10.1016/j.jneuroim.2016.10.004

All-trans retinoic acid (ATRA) prevents lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment in aged rats

J Neuroimmunol. 2016 Nov 15:300:21-29. doi: 10.1016/j.jneuroim.2016.10.004. Epub 2016 Oct 8.

Authors

Nassima Behairi¹, Mourad Belkhelfa², Hayet Rafa³, Moussa Labsi⁴, Nahla Deghbar⁵, Nora Bouzid⁶, Hamida Mesbah-Amroun⁷, Chafia Touil-Boukoffa⁸

Affiliations

¹ University of Sciences and Technology Houari Boumediene (USTHB), Faculty of Biological Sciences, Cellular and Molecular Biology Laboratory, Cytokines and NO Synthases, Immunity and Pathogeny Team, Algiers, Algeria. Electronic address: behairi_nassima@hotmail.com.
² University of Sciences and Technology Houari Boumediene (USTHB), Faculty of Biological Sciences, Cellular and Molecular Biology Laboratory, Cytokines and NO Synthases, Immunity and Pathogeny Team, Algiers, Algeria. Electronic address: mbelkhelfa@yahoo.fr.
³ University of Sciences and Technology Houari Boumediene (USTHB), Faculty of Biological Sciences, Cellular and Molecular Biology Laboratory, Cytokines and NO Synthases, Immunity and Pathogeny Team, Algiers, Algeria. Electronic address: rafa_hayet2002@yahoo.fr.
⁴ University of Sciences and Technology Houari Boumediene (USTHB), Faculty of Biological Sciences, Cellular and Molecular Biology Laboratory, Cytokines and NO Synthases, Immunity and Pathogeny Team, Algiers, Algeria. Electronic address: moussalabsi@yahoo.fr.
⁵ University of Sciences and Technology Houari Boumediene (USTHB), Faculty of Biological Sciences, Cellular and Molecular Biology Laboratory, Cytokines and NO Synthases, Immunity and Pathogeny Team, Algiers, Algeria. Electronic address: ndeghbar@usthb.dz.
⁶ Hammoud Nafissa Hospital, Pathology Department, Algiers, Algeria. Electronic address: bouzidanap@hotmail.fr.
⁷ University of Sciences and Technology Houari Boumediene (USTHB), Faculty of Biological Sciences, Cellular and Molecular Biology Laboratory, Cytokines and NO Synthases, Immunity and Pathogeny Team, Algiers, Algeria. Electronic address: amrounhamida@yahoo.com.
⁸ University of Sciences and Technology Houari Boumediene (USTHB), Faculty of Biological Sciences, Cellular and Molecular Biology Laboratory, Cytokines and NO Synthases, Immunity and Pathogeny Team, Algiers, Algeria. Electronic address: touilboukoffa@yahoo.fr.

PMID: 27806872
DOI: 10.1016/j.jneuroim.2016.10.004

Abstract

We aimed to investigate preventive effects of All-trans retinoic acid (ATRA) on a lipopolysaccharide (LPS)-induced aged neuroinflammation model. We analyzed behavior, systemic nitric oxide (NO) production, cerebral NO synthase (NOS2) and β-amyloid (Aβ) 1-42 expression and tissue integrity in the neuroinflammation model pretreated with ATRA (150μg/ml/rat/day) for 30days. Our results showed that LPS treatment (500μg/kg/day) for 7days disturbed memory, enhanced systemic NO production, NOS2 and Aβ 1-42 cerebral expression and generated an Alzheimer's disease (AD)-like neuronal degeneration. Interestingly, ATRA pretreatment prevented the LPS-induced deleterious effects. ATRA could be a potent preventive approach in AD.

Keywords: Aging; All-trans retinoic acid; Alzheimer's disease; Inducible nitric oxide synthase; Neuroinflammation.

MeSH terms

Aging / drug effects
Aging / metabolism*
Aging / pathology
Alzheimer Disease / metabolism*
Alzheimer Disease / pathology
Alzheimer Disease / prevention & control
Amyloid beta-Peptides / antagonists & inhibitors
Amyloid beta-Peptides / biosynthesis*
Animals
Brain / drug effects
Brain / metabolism
Brain / pathology
Inflammation / metabolism
Inflammation / pathology
Inflammation / prevention & control
Lipopolysaccharides / toxicity
Male
Memory Disorders / metabolism*
Memory Disorders / pathology
Memory Disorders / prevention & control
Neuroprotective Agents / pharmacology
Neuroprotective Agents / therapeutic use*
Nitric Oxide Synthase Type II / biosynthesis
Peptide Fragments / antagonists & inhibitors
Peptide Fragments / biosynthesis*
Rats
Rats, Wistar
Tretinoin / therapeutic use*

Substances

Amyloid beta-Peptides
Lipopolysaccharides
Neuroprotective Agents
Peptide Fragments
amyloid beta-protein (1-42)
Tretinoin
Nitric Oxide Synthase Type II
Nos2 protein, rat