Curcumin treatment leads to better cognitive and mood function in a model of Gulf War Illness with enhanced neurogenesis, and alleviation of inflammation and mitochondrial dysfunction in the hippocampus

Abstract

Diminished cognitive and mood function are among the most conspicuous symptoms of Gulf War Illness (GWI). Our previous studies in a rat model of GWI have demonstrated that persistent cognitive and mood impairments are associated with substantially declined neurogenesis, chronic low-grade inflammation, increased oxidative stress and mitochondrial dysfunction in the hippocampus. We tested the efficacy of curcumin (CUR) to maintain better cognitive and mood function in a rat model of GWI because of its neurogenic, antiinflammatory, antioxidant, and memory and mood enhancing properties. Male rats were exposed daily to low doses of GWI-related chemicals, pyridostigmine bromide, N,N-diethyl-m-toluamide (DEET) and permethrin, and 5-minutes of restraint stress for 28 days. Animals were next randomly assigned to two groups, which received daily CUR or vehicle treatment for 30 days. Animals also received 5'-bromodeoxyuridine during the last seven days of treatment for analysis of neurogenesis. Behavioral studies through object location, novel object recognition and novelty suppressed feeding tests performed sixty days after treatment revealed better cognitive and mood function in CUR treated GWI rats. These rats also displayed enhanced neurogenesis and diminished inflammation typified by reduced astrocyte hypertrophy and activated microglia in the hippocampus. Additional studies showed that CUR treatment to GWI rats enhanced the expression of antioxidant genes and normalized the expression of multiple genes related to mitochondrial respiration. Thus, CUR therapy is efficacious for maintaining better memory and mood function in a model of GWI. Enhanced neurogenesis, restrained inflammation and oxidative stress with normalized mitochondrial respiration may underlie better memory and mood function mediated by CUR treatment.

Parkinson's disease, aging and adult neurogenesis: Wnt/β‐catenin signalling as the key to unlock the mystery of endogenous brain repair

“…Curcumin‐loaded nanoparticles powerfully induce adult neurogenesis and reverse cognitive deficits in an Alzheimer's disease model via the activation of WβC‐signalling pathway (Tiwari et al, , ). The ability of curcumin treatment to ameliorate cognitive and mood function was previously associated with increased neurogenesis as well as mitigation of inflammation and mitochondrial dysfunction in the rodent hippocampus (Kodali et al, ).…”

“…Kaur et al (2017) addressed the potential of coupling optogenetics and light-sheet microscopy to study Wnt signalling during embryogenesis, showing that WβC-signalling is required not only for Drosophila pattern formation, but also for maintenance later in development. Additionally, Zhang, Huang, et al (2016c) Ameliorates cognitive function, enhances neurogenesis, mitigates inflammation and mitochondrial dysfunction in hippocampus in a rodent model of gulf war illeness; WβC-AC involvement to be elucidated Kodali et al (2018) Exercise, environmental enrichment…”

Intranasally Administered Human MSC-Derived Extracellular Vesicles Pervasively Incorporate into Neurons and Microglia in both Intact and Status Epilepticus Injured Forebrain

“…Six hours after SE, animals in both naïve and SE groups underwent intracardiac perfusions with 4% paraformaldehyde. The brains were dissected, post-fixed in 4% paraformaldehyde overnight, and processed for sectioning using a cryostat [52][53][54][55][56]. Thirty micrometer-thick coronal sections were cut through the entire forebrain and collected serially in 24-well plates containing the phosphate buffer.…”

“…Optical Z-sections (1-µm thick) were sampled from different forebrain regions using a Nikon confocal microscope [53][54][55][56]. Z-stacks were captured from three different fields in every region of the forebrain for every marker analyzed in the study.…”

Effects of minocycline on neuroinflammation, gut microbiome and hippocampal neurogenesis in rats with Gulf War Illness

“…For GWI patients, the levels of multiple proin ammatory biomarkers in the blood also increased signi cantly 10 . More importantly, enhanced neurogenesis, and alleviation of neuroin ammation by curcumin treatment could leads to better cognitive and mood function in GWI rats 11 . Taken together, the results of these studies have indicated that over activation of neuroin ammation and impaired neurogenesis in the adult hippocampus might be the key biological processes involved in GWI pathophysiology and may as the potential therapeutic targets for treating GWI.…”