Role of Hypothalamic-Pituitary-Adrenal Axis, Hypothalamic-Pituitary-Gonadal Axis and Insulin Signaling in the Pathophysiology of Alzheimer’s Disease

Ahmad, Mir Hilal; Fatima, Mahino; Mondal, Amal Chandra

doi:10.1159/000495521

Cited by 39 publications

(19 citation statements)

References 109 publications

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“…Additionally, T2DM is a major risk factor for developing AD and T2DM patients often show symptoms of cognitive decline, which might be partially mediated by peripheral and central inflammation 11 . Another aspect linking AD to glucose metabolism is the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, leading to alterations in glucocorticoid (GC) levels 12 . GCs act as functional antagonists of insulin, whereupon chronically elevated levels of GCs cause insulin resistance and glucose intolerance 13 .…”

Section: Introductionmentioning

confidence: 99%

Chia seeds as a potential cognitive booster in the APP23 Alzheimer’s disease model

Schreyer

Klein

Pfeffer

et al. 2020

Sci Rep

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Glucose hypometabolism potentially contributes to Alzheimer’s disease (AD) and might even represent an underlying mechanism. Here, we investigate the relationship of diet-induced metabolic stress and AD as well as the therapeutic potential of chia seeds as a modulator of glucose metabolism in the APP23 mouse model. 4–6 (pre-plaque stage, PRE) and 28–32 (advanced-plaque stage, ADV) weeks old APP23 and wild type mice received pretreatment for 12 weeks with either sucrose-rich (SRD) or control diet, followed by 8 weeks of chia seed supplementation. Although ADV APP23 mice generally showed functioning glucose homeostasis, they were more prone to SRD-induced glucose intolerance. This was accompanied by elevated corticosterone levels and mild insulin insensitivity. Chia seeds improved spatial learning deficits but not impaired cognitive flexibility, potentially mediated by amelioration of glucose tolerance, attenuation of corticosterone levels and reversal of SRD-induced elevation of pro-inflammatory cytokine levels. Since cognitive symptoms and plaque load were not aggravated by SRD-induced metabolic stress, despite enhanced neuroinflammation in the PRE group, we conclude that impairments of glucose metabolism do not represent an underlying mechanism of AD in this mouse model. Nevertheless, chia seeds might provide therapeutic potential in AD as shown by the amelioration of cognitive symptoms.

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Section: Introductionmentioning

confidence: 99%

Chia seeds as a potential cognitive booster in the APP23 Alzheimer’s disease model

Schreyer

Klein

Pfeffer

et al. 2020

Sci Rep

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“…HPG axis hormone receptors (including steroid hormones, human chorionic gonadotropin, LH, and GnRH) are concentrated in the limbic system, especially hippocampal pyramidal neurons, and are involved in regulating the growth, structure, and function of the adult brain. These sections are very sensitive to AD pathology (17)(18)(19).…”

Section: Hypothalamic-pituitary-gonadal Axis and Estrogenmentioning

confidence: 99%

“…There is an inverse relationship between LH and memory, and most studies show a correlation between serum LH concentration and amyloid-beta plasma accumulation and deposition (94). Elevated LH levels are involved in Aβ metabolism and accumulation and are associated with an increased risk of AD (17). Some studies suggest a link between LH and BDNF in the hippocampus, and these studies suggest that estrogen-increasing and LH-lowering treatments may both require BDNF signaling to improve spatial memory (95).…”

Section: Lh/fsh Ratiomentioning

confidence: 99%

Investigation of common risk factors between polycystic ovary syndrome and Alzheimer's disease

Sarahian

Sarvazad

Sajadi

et al. 2021

Preprint

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The most common endocrine disorder among women is Polycystic ovary syndrome (PCOS), characterized by hyperandrogenism, chronic ovulation, and/or ultrasound evidence of small ovarian cysts. Obesity and insulin resistance are also the main factors influencing the clinical manifestations of this syndrome. High intakes of fat have been linked to more significant cognitive decline in old age, and due to the growing elderly population, maintaining long-term optimal cognitive function is very important. Alzheimer's disease (AD) is the most typical progressive neurodegenerative disorder of the brain, and recent studies suggest a relationship between endocrinal dysregulation and neuronal loss during AD pathology. In this narrative review, the international databases, including Google Scholar, Scopus, PubMed, and Web of Science databases, were searched for retrieving the relevant studies. According to the factors involved in Alzheimer's and PCOS, it seems that both disorders may share some common risk factors. In this study, the relevant studies' summaries were categorized to discuss the possible pathways that may explain the association between Alzheimer's and PCOS signs/symptoms and complications. Future preclinical studies are needed to investigate the exact underlining mechanisms related to PCOS and Alzheimer's association.

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“…Studies have been conducted through dexamethasone/corticotrophin‐releasing hormone (DEX/CRH) test and insulin resistance evaluated by the homeostasis model assessment of insulin resistance (HOMA‐R) to demonstrate that HPA axis dysfunction is associated with insulin in patients with depression 14 . Insulin has a certain degree of influence on hormones involved in HPA negative feedback 58 …”

Section: Effect Of Insulin On Depressionmentioning

confidence: 99%

Potential role of insulin on the pathogenesis of depression

et al. 2020

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| INTRODUC TI ONDiabetes is a metabolic disease characterized by hyperglycaemia due to the defect of insulin secretion or impaired insulin biological effect. A survey has shown that about 30% of people with diabetes also suffer from depression and 10% have severe depression, which suggests a close relationship between the two diseases. 1,2 The mechanism of depression as a complication of diabetes is not completely clear, but studies have found that insulin deficiency or insulin resistance is the symptom that can also be observed in major depression disorder. [3][4][5] Insulin is the only hormone in the human body that reduces the blood glucose level and promotes the synthesis of glycogen, fat and protein. Several studies found that insulin had the ability to affect the nervous system. 6-8 Insulin receptors were distributed in other parts of the brain, except for the parts related to food intake and energy. 9-11 Experiments have gradually revealed other functions of insulin in the brain, for instance promoting memory, protecting neurons, regulating synaptic plasticity and maintaining HPA axis homeostasis. [12][13][14] These effects of insulin may provide a background for its relationship with depression. 15,16 In this case, although there is no direct evidence supporting the link between insulin and treatment for depression, more and more researches support this hypothesis. Here, we review the relationship between insulin signalling and neurophysiological homeostasis, neurotrophic metabolism, cellular pathways and some survey statistics.The exploration of these links and the validation of more relevant mechanisms will develop a new impact on the way of the diagnosis and treatment of depression. | IN SULIN AND DEPRE SS I ONAs early as 1980s, many evidences proved that insulin influenced depression and functional insulin receptors were widely present in the brain. [17][18][19] Data from clinical and epidemiological studies demonstrate a two-way link between emotion and metabolic dysfunction. In young depression patients, insulin sensitivity is significantly decreased. 20,21 Compared with "low insulin" (1.5 mU/kg × min), "high insulin" (15 mU/kg × min) induces a more pronounced of the ability to remember word lists in human being. 22 Intranasal delivery of insulin in awake mice can transmit regulatory and metabolic AbstractThe regulation of insulin on depression and depression-like behaviour has been widely reported. Insulin and activation of its receptor can promote learning and memory, affect the hypothalamic-pituitary-adrenal axis (HPA) balance, regulate the secretion of neurotrophic factors and neurotransmitters, interact with gastrointestinal microbiome, exert neuroprotective effects and have an impact on depression. However, the role of insulin on depression remains largely unclear. Therefore, in this review, we summarized the potential role of insulin on depression. It may provide new insight for clarifying role of insulin on the pathogenesis of depression.

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Role of Hypothalamic-Pituitary-Adrenal Axis, Hypothalamic-Pituitary-Gonadal Axis and Insulin Signaling in the Pathophysiology of Alzheimer’s Disease

Cited by 39 publications

References 109 publications

Chia seeds as a potential cognitive booster in the APP23 Alzheimer’s disease model

Chia seeds as a potential cognitive booster in the APP23 Alzheimer’s disease model

Investigation of common risk factors between polycystic ovary syndrome and Alzheimer's disease

Potential role of insulin on the pathogenesis of depression

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