Lipidomic Profiling of Phosphocholine Containing Brain Lipids in Mice with Sensorimotor Deficits and Anxiety-Like Features After Exposure to Gulf War Agents

Abdullah, Laila; Evans, James E.; Bishop, Alex; Reed, Jon; Crynen, Gogce; Phillips, John H.; Pelot, Robert; Mullan, Myles; Ferro, Austin; Mullan, C. Mc; Mullan, Michael; Ait‐Ghezala, Ghania; Crawford, Fiona

doi:10.1007/s12017-012-8192-z

Cited by 68 publications

(70 citation statements)

References 44 publications

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“…further showed that PM and DEET (but not PB) exposure can greatly inhibit the proliferation of NSCs. Interestingly, cognitive dysfunction observed in this rat model contrasts with a recent study in C57BL/6 mouse model where exposure to similar doses of chemicals and stress did not impair cognitive function but enhanced anxiety when examined 20 days after the exposure (Abdullah et al, 2012). The discrepancy between the two studies likely reflects differences in animal species and timing of behavioral analyses.…”

Section: Discussioncontrasting

confidence: 85%

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Mood and Memory Deficits in a Model of Gulf War Illness Are Linked with Reduced Neurogenesis, Partial Neuron Loss, and Mild Inflammation in the Hippocampus

Parihar

Hattiangady

Shuai

et al. 2013

Neuropsychopharmacol

155

190

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Impairments in mood and cognitive function are the key brain abnormalities observed in Gulf war illness (GWI), a chronic multisymptom health problem afflicting ∼25% of veterans who served in the Persian Gulf War-1. Although the precise cause of GWI is still unknown, combined exposure to a nerve gas prophylaxis drug pyridostigmine bromide (PB) and pesticides DEET and permethrin during the war has been proposed as one of the foremost causes of GWI. We investigated the effect of 4 weeks of exposure to Gulf war illness-related (GWIR) chemicals in the absence or presence of mild stress on mood and cognitive function, dentate gyrus neurogenesis, and neurons, microglia, and astrocytes in the hippocampus. Combined exposure to low doses of GWIR chemicals PB, DEET, and permethrin induced depressive- and anxiety-like behavior and spatial learning and memory dysfunction. Application of mild stress in the period of exposure to chemicals exacerbated the extent of mood and cognitive dysfunction. Furthermore, these behavioral impairments were associated with reduced hippocampal volume and multiple cellular alterations such as chronic reductions in neural stem cell activity and neurogenesis, partial loss of principal neurons, and mild inflammation comprising sporadic occurrence of activated microglia and significant hypertrophy of astrocytes. The results show the first evidence of an association between mood and cognitive dysfunction and hippocampal pathology epitomized by decreased neurogenesis, partial loss of principal neurons, and mild inflammation in a model of GWI. Hence, treatment strategies that are efficacious for enhancing neurogenesis and suppressing inflammation may be helpful for alleviation of mood and cognitive dysfunction observed in GWI.

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Section: Discussioncontrasting

confidence: 85%

“…Additional factors may also be involved. For example, a recent lipidomics study reported that regulation of acetylcholine regulator and signaling pathways undergo alterations with exposure to GWIR chemicals (Abdullah et al, 2012).…”

Section: Other Factors Contributing To Gwir Chemical-mediated Hippocamentioning

confidence: 99%

Mood and Memory Deficits in a Model of Gulf War Illness Are Linked with Reduced Neurogenesis, Partial Neuron Loss, and Mild Inflammation in the Hippocampus

Parihar

Hattiangady

Shuai

et al. 2013

Neuropsychopharmacol

155

190

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“…The Folch extraction of serum and plasma samples was performed as previously described [66-68] using the Folch method [69] following an addition of di-14:0 fatty acid (FA) containing PC and PE (Matreya, Pleasant Gap, PA), di-16:0 PI, and 14:0 LPC (Avanti, Albaster, AL) as internal standards. High-pressure liquid chromatography (HPLC) was achieved using a 1mm ID x 10 cm column containing Pinnacle II 3 μm silica particles (Restek, Bellefonte, PA, USA).…”

Section: Methodsmentioning

confidence: 99%

APOE ε4 specific imbalance of arachidonic acid and docosahexaenoic acid in serum phospholipids identifies individuals with preclinical Mild Cognitive Impairment/Alzheimer’s Disease

Abdullah

Evans

Emmerich

et al. 2017

Aging

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This study was designed to explore the influence of apolipoprotein E (APOE) on blood phospholipids (PL) in predicting preclinical Alzheimer's disease (AD). Lipidomic analyses were also performed on blood from an AD mouse model expressing human APOE isoforms (EFAD) and five AD mutations and from 195 cognitively normal participants, 23 of who converted to mild cognitive impairment (MCI)/AD within 3 years. APOE ε4-carriers converting to MCI/AD had high arachidonic acid (AA)/docosahexaenoic acid (DHA) ratios in PL compared to cognitively normal ε4 and non-ε4 carriers. Arachidonic acid and DHA containing PL species, ε4-status and Aβ42/Aβ40 ratios provided 91% accuracy in detecting MCI/AD. Fish oil/omega-3 fatty acid consumption was associated with lower AA/DHA ratios even among ε4 carriers. High plasma AA/DHA ratios were observed in E4FAD compared to EFAD mice with other isoforms. In particular, alterations in plasma AA and DHA containing PL species were also observed in the brains of E4FAD mice compared to E3FAD mice. Despite the small sample size and a short follow-up, these results suggest that blood PL could potentially serve as biomarkers of preclinical MCI/AD.

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“…This test was performed as described elsewhere (25,26). Mice were allowed to acclimate to the experimental paradigm using a single trial at 5 rpm fixed speed over 5 min.…”

Section: Rotarodmentioning

confidence: 99%

“…For these analyses, each mouse was a random factor, and exposure and time (days) were fixed factors. As described previously (26), for lipidomics, dimension reduction and multicolinearity issues were resolved using principal component analysis (PCA). Each component was extracted using the Anderson-Rubin method and examined as an outcome measure using MLM while adjusting for fixed (injury and technical replication) and random (mouse) factors.…”

Section: Statistical Analysesmentioning

confidence: 99%

Lipidomic analyses identify injury‐specific phospholipid changes 3 mo after traumatic brain injury

et al. 2014

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Phospholipid (PL) abnormalities are observed in the cerebrospinal fluid of patients with traumatic brain injury (TBI), suggesting their role in TBI pathology. Therefore, PL levels were examined in a TBI mouse model that received 1.8 mm deep controlled cortical impact injury or craniectomy only (control). The rotarod and Barnes maze acquisition and probe tests were performed within 2 wk after injury, with another probe test performed 3 mo postinjury. Liquid chromatography/mass spectrometry analyses were performed on lipid extracts from several brain regions and plasma from injured and control mice collected at 3 mo postinjury. Compared to controls, injured mice with sensorimotor and learning deficits had decreased levels of cortical and cerebellar phosphatidylcholine (PC) and phosphatidylethanolamine (PE) levels, while hippocampal PC, sphingomyelin and PE levels were elevated. Ether PE levels were lower in the cortices and plasma of injured animals. Polyunsaturated fatty acid-containing PC and PE species, particularly ratios of docosahexaenoic acid (DHA) to arachidonic acid, were lower in the hippocampi and cortices and plasma of injured mice. Given the importance of DHA in maintaining neuronal function and resolving inflammation and of peroxisomes in synthesis of ether PLs, normalizing these PLs may be a useful strategy for treating the chronic pathology of TBI.-Abdullah, L., Evans, J. E., Ferguson, S., Mouzon, B., Montague, H., Reed, J., Crynen, G., Emmerich, T., Crocker, M., Pelot, R., Mullan, M., Crawford, F. Lipidomic analyses identify injury-specific phospholipid changes 3 months after traumatic brain injury. FASEB J. 28, 5311-5321 (2014). www.fasebj.org Key Words: controlled cortical impact ⅐ mass spectrometry ⅐ phosphatidylcholine ⅐ phosphatidylethanolamine ⅐ phosphatidylinositol ⅐ sphingomyelin Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in the United States among adults from both the civilian and military populations. Due to the improvements made in military body armor and combat helmets over the past 2 decades, the rate of severe TBI associated with Iraq and Afghanistan deployments has decreased to 1% of the total TBI sustained by military personnel, a rate that is lower than those reported for previous deployments (1-3). Estimates from the U.S. Centers for Disease Control and Prevention suggest that severe TBI remains an important issue in the civilian population. In 2010, 2.5 million admissions to emergency departments were due to TBI (4) contributing to about a third of injury related deaths in the United States. The annual U.S. costs associated with TBI are estimated to be $75 billion, largely attributed to medical care, loss of productivity, and long-term disability (5). Although mild TBI occurs more frequently than severe TBI, the latter has the largest adverse effect on the activities of daily living of injured individuals and accounts for 90% of the total TBI-related medical costs (5). The primary injury is caused by the immediate force of the trauma a...

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Lipidomic Profiling of Phosphocholine Containing Brain Lipids in Mice with Sensorimotor Deficits and Anxiety-Like Features After Exposure to Gulf War Agents

Cited by 68 publications

References 44 publications

Mood and Memory Deficits in a Model of Gulf War Illness Are Linked with Reduced Neurogenesis, Partial Neuron Loss, and Mild Inflammation in the Hippocampus

Mood and Memory Deficits in a Model of Gulf War Illness Are Linked with Reduced Neurogenesis, Partial Neuron Loss, and Mild Inflammation in the Hippocampus

APOE ε4 specific imbalance of arachidonic acid and docosahexaenoic acid in serum phospholipids identifies individuals with preclinical Mild Cognitive Impairment/Alzheimer’s Disease

Lipidomic analyses identify injury‐specific phospholipid changes 3 mo after traumatic brain injury

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