A Stress Syndrome Prototype Reflects Type 3 Diabetes and Ischemic Stroke Risk: The SABPA Study

Malan, Leoné; Hamer, Mark; Känel, Roland von; Wyk, Roelof D. van; Sumner, Anne E.; Nilsson, Peter M.; Lambert, Gavin; Steyn, Herman; Badenhorst, C. J.; Malan, Nico

doi:10.3390/biology10020162

Cited by 6 publications

(7 citation statements)

References 66 publications

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“…The relationship between insulin resistance and AD, also called T3DM [15,16], is well recognized [12][13][14] and a subject of ongoing research. In this perspective, a recent epidemiological study has reinforced the detrimental role of chronic stress in T3DM and neurodegeneration [53]. Although there is speculation about the causal or consequential effect of insulin on the progression of AD, it still remains unclear when changes in insulin functionality occur in the AD timeline [54].…”

Section: Discussionmentioning

confidence: 99%

Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer’s Disease

Hendrickx

Moudt

Calus

et al. 2021

IJMS

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Increasing epidemiological evidence highlights the association between systemic insulin resistance and Alzheimer’s disease (AD). As insulin resistance can be caused by high-stress hormone levels and since hypercortisolism appears to be an important risk factor of AD, we aimed to investigate the systemic insulin functionality and circulating stress hormone levels in a mutant humanized amyloid precursor protein (APP) overexpressing (hAPP23+/−) AD mouse model. Memory and spatial learning of male hAPP23+/− and C57BL/6 (wild type, WT) mice were assessed by a Morris Water Maze (MWM) test at the age of 4 and 12 months. The systemic metabolism was examined by intraperitoneal glucose and insulin tolerance tests (GTT, ITT). Insulin and corticosterone levels were determined in serum. In the hippocampus, parietal and occipital cortex of hAPP23+/− brains, amyloid-beta (Aβ) deposits were present at 12 months of age. MWM demonstrated a cognitive decline in hAPP23+/− mice at 12 but not at 4 months, evidenced by increasing total path lengths and deteriorating probe trials compared to WT mice. hAPP23+/− animals presented increased serum corticosterone levels compared to WT mice at both 4 and 12 months. hAPP23+/− mice exhibited peripheral insulin resistance compared to WT mice at 4 months, which stabilized at 12 months of age. Serum insulin levels were similar between genotypes at 4 months of age but were significantly higher in hAPP23+/− mice at 12 months of age. Peripheral glucose homeostasis remained unchanged. These results indicate that peripheral insulin resistance combined with elevated circulating stress hormone levels could be potential biomarkers of the pre-symptomatic phase of AD.

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Section: Discussionmentioning

confidence: 99%

Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer’s Disease

Hendrickx

Moudt

Calus

et al. 2021

IJMS

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“…The chronic stress risk phenotype score (index) revealed discriminatory ability for the positive prediction of chronic stress and stroke risk (area-under-the-curve 0.77, 85% sensitivity) (Malan & Malan 2021:PCT/IB2020/057269).…”

Section: Reviewed Coping and Chronic Stress Methodologymentioning

confidence: 99%

“…Until recently, the ability to identify chronic stress risk per se remained a challenge. Hence identifying the chronic stress phenotype (Malan & Malan 2021) might aid medical and pastoral counselling interventions, to improve psychophysiological well-being. Amid the potential increase of pandemic related chronic stress, anxiety and depression, this article aimed to identify positive coping skills that could help the Christian handle prevalent chronic stress from a faith perspective.…”

Section: Chronic Stress Anxiety and Depression During And Beyond Covi...mentioning

confidence: 99%

“…A literature study was conducted to identify positive and negative coping strategies, and to call attention to the detrimental effects of chronic stress. Recently, a supportive novel measure, the chronic stress phenotype (stress phenotype; Malan & Malan 2021:PCT/IB2020/057269) was highlighted to reflect adverse effects of chronic stress (Malan et al 2020:5;2021a:16;2021b:13) that may be induced by COVID-19 threats and restrictions. Certain Bible passages and theological perspectives regarding spiritual coping were explored, to identify traces of the fight-or-flight response in the Garden of Gethsemane.…”

Section: Introductionmentioning

confidence: 99%

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Coping with chronic stress during COVID-19 and beyond – A faith perspective

Roux

Denton²,

Malan³

et al. 2022

In die Skriflig / In Luce Verbi

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Spiritual coping has been defined as an individual’s ability to utilise faith in God combined with certain Christian beliefs and religious practices to appraise, understand, and effectively cope with stress. We aimed to show the Christian how specific spiritual coping strategies and religious practices could be used to effectively assess and handle chronic stress from a faith perspective amid the ongoing coronavirus disease 2019 (COVID-19) pandemic and beyond. A literature study was conducted to identify positive and negative coping strategies during the COVID-19 era and highlighted the adverse effects of chronic stress and defensiveness. Recent findings on religion, the validated bio-engineered chronic stress phenotype, the Coping Strategy Indicator (CSI), Africultural Coping Systems Inventory (ACSI) and the effect of spiritual coping skills were assessed. In addition, certain Bible passages and theological perspectives regarding spiritual coping were explored to identify traces of the fight-or-flight response in the Garden of Gethsemane. The novel chronic stress phenotype reflecting stroke risk, could determine the prevalence of chronic stress. Positive coping strategies were identified, to show how positive spiritual coping skills could be utilised from a faith perspective, in coping with chronic stress amid COVID-19 and beyond. The Believe-Belong-Behave pastoral model, consisting of individual skills, corporate practices, and practical action steps, showed the Christian how certain spiritual coping skills and practices could be implemented during stress coping. The scriptural insights gained from this study, combined with the pastoral model reviewed, could offer a harmonious contribution toward the Christian’s ability to utilise spiritual coping strategies amid COVID-19 chronic stress-induced symptoms and complexities.Contribution: This article used an inter-disciplinary approach to compare recent findings within Theology, Neurophysiology, Bio-engineering, and Psychology regarding religion, stress-phenotyping, positive stress-coping and mental health. The scriptural foundation encouraged a faith-in-action response to chronic stress during the ongoing COVID-19 pandemic and beyond.

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“…Later, we used a TaqMan® Array to uncover changes in the transcriptome caused by the absence of JNK1 and JNK3, as well as the individual and synergistic effects of a chronic feeding with a high-fat diet (HFD). Feeding of a HFD was chosen as a model of metabolic stress and potential contributor to the appearance of sporadic forms of neurodegeneration based on preclinical, clinical and epidemiological reported data (Henneberg and Hoyer 1995 ; Hoyer et al 1996 ; Felice and Lourenco 2015 ; Grillo et al 2015 ; Ott et al 1999 ; Willmann et al 2020 ; Kaplan et al 2022 ; Akinola 2016 ; Milstein and Ferris 2021 ; Malan et al 2021 ). In the end, the results allowed us to describe further the pathways affected by loss of function of JNK1 and JNK3 and thus, we were able to gather more evidence on their suitability as targets for pharmacological approaches.…”

Section: Introductionmentioning

confidence: 99%

JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function

Busquets

Espinosa-Jiménez

Ettcheto

et al. 2022

Mol Med

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Background and aim The appearance of alterations in normal metabolic activity has been increasingly considered a risk factor for the development of sporadic and late-onset neurodegenerative diseases. In this report, we induced chronic metabolic stress by feeding of a high-fat diet (HFD) in order to study its consequences in cognition. We also studied the effects of a loss of function of isoforms 1 and 3 of the c-Jun N-terminal Kinases (JNK), stress and cell death response elements. Methods Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice at 9 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-GTT and IP‑ITT) were performed to evaluate peripheral biometrics. Additionally, cognitive behavioral tests and analysis of spine density were performed to assess cognitive function. Molecular studies were carried out to confirm the effects of metabolic stressors in the hippocampus relative to cognitive loss. Results Our studies demonstrated that HFD in Jnk3−/− lead to synergetic responses. Loss of function of JNK3 led to increased body weight, especially when exposed to an HFD and they had significantly decreased response to insulin. These mice also showed increased stress in the endoplasmic reticulum and diminished cognitive capacity. However, loss of function of JNK1 promoted normal or heightened energetic metabolism and preserved cognitive function even when chronically metabolically stressed. Conclusions Downregulation of JNK3 does not seem to be a suitable target for the modulation of energetic-cognitive dysregulations while loss of function of JNK1 seems to promote a good metabolic-cognitive profile, just like resistance to the negative effects of chronic feeding with HFD.

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A Stress Syndrome Prototype Reflects Type 3 Diabetes and Ischemic Stroke Risk: The SABPA Study

Cited by 6 publications

References 66 publications

Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer’s Disease

Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer’s Disease

Coping with chronic stress during COVID-19 and beyond – A faith perspective

JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function

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