Abstract:Diabetes mellitus is a metabolic disease characterized by hyperglycemia due to defects in insulin secretion or its action. Complications from long-term diabetes consist of numerous biochemical, molecular, and functional tissue alterations, including inflammation, oxidative stress, and neuropathic pain. There is also a link between diabetes mellitus and vascular dementia or Alzheimer’s disease. Hence, it is important to treat diabetic complications using drugs which do not aggravate symptoms induced by the dise… Show more
“…Glucose transporters have also been identified at the BBB endothelial cells; GLUT3 (Gerhart, Broderius, Borson, & Drewes, ; Shawahna et al, ), GLUT4 (Ngarmukos, Baur, & Kumagai, ), SGLT1 (Nishizaki & Matsuoka, ; Yamazaki, Ogihara, Harada, & Tokuyama, ), and SGLT2 (Enerson & Drewes, ; Jurcovicova, ) have been reported in lower levels. Insulin sensitive GLUT4 expression has also been shown to be at the BBB of the ventromedial hypothalamus indicating its role in brain sensing of blood glucose levels (Keeney et al, ; Ngarmukos et al, ; Patel, Gupta, & Udayabanu, ; Sałat et al, ). Neurons mainly express GLUT3, a high “affinity” and high capacity glucose transporter in comparison with GLUT1 (Maher, Davies‐Hill, & Simpson, ; Simpson, Carruthers, & Vannucci, ).…”
Alzheimer's disease (AD) is the most common cause of dementia and one of the most important causes of morbidity and mortality among the aging population. AD diagnosis is made post-mortem, and the two pathologic hallmarks, particularly evident in the end stages of the illness, are amyloid plaques and neurofibrillary tangles. Currently, there is no curative treatment for AD. Additionally, there is a strong relation between oxidative stress, metabolic syndrome, and AD. The high levels of circulating lipids and glucose imbalances amplify lipid peroxidation that gradually diminishes the antioxidant systems, causing high levels of oxidative metabolism that affects cell structure, leading to neuronal damage. Accumulating evidence suggests that AD is closely related to a dysfunction of both insulin signaling and glucose metabolism in the brain, leading to an insulin-resistant brain state. Four drugs are currently used for this pathology: Three FDA-approved cholinesterase inhibitors and one NMDA receptor antagonist. However, wide varieties of antioxidants are promissory to delay or prevent the symptoms of AD and may help in treating the disease. Therefore, therapeutic efforts to achieve attenuation of oxidative stress could be beneficial in AD treatment, attenuating Aβ-induced neurotoxicity and improve neurological outcomes in AD. The term inflammaging characterizes a widely accepted paradigm that aging is accompanied by a low-grade chronic up-regulation of certain pro-inflammatory responses in the absence of overt infection, and is a highly significant risk factor for both morbidity and mortality in the elderly.
“…Glucose transporters have also been identified at the BBB endothelial cells; GLUT3 (Gerhart, Broderius, Borson, & Drewes, ; Shawahna et al, ), GLUT4 (Ngarmukos, Baur, & Kumagai, ), SGLT1 (Nishizaki & Matsuoka, ; Yamazaki, Ogihara, Harada, & Tokuyama, ), and SGLT2 (Enerson & Drewes, ; Jurcovicova, ) have been reported in lower levels. Insulin sensitive GLUT4 expression has also been shown to be at the BBB of the ventromedial hypothalamus indicating its role in brain sensing of blood glucose levels (Keeney et al, ; Ngarmukos et al, ; Patel, Gupta, & Udayabanu, ; Sałat et al, ). Neurons mainly express GLUT3, a high “affinity” and high capacity glucose transporter in comparison with GLUT1 (Maher, Davies‐Hill, & Simpson, ; Simpson, Carruthers, & Vannucci, ).…”
Alzheimer's disease (AD) is the most common cause of dementia and one of the most important causes of morbidity and mortality among the aging population. AD diagnosis is made post-mortem, and the two pathologic hallmarks, particularly evident in the end stages of the illness, are amyloid plaques and neurofibrillary tangles. Currently, there is no curative treatment for AD. Additionally, there is a strong relation between oxidative stress, metabolic syndrome, and AD. The high levels of circulating lipids and glucose imbalances amplify lipid peroxidation that gradually diminishes the antioxidant systems, causing high levels of oxidative metabolism that affects cell structure, leading to neuronal damage. Accumulating evidence suggests that AD is closely related to a dysfunction of both insulin signaling and glucose metabolism in the brain, leading to an insulin-resistant brain state. Four drugs are currently used for this pathology: Three FDA-approved cholinesterase inhibitors and one NMDA receptor antagonist. However, wide varieties of antioxidants are promissory to delay or prevent the symptoms of AD and may help in treating the disease. Therefore, therapeutic efforts to achieve attenuation of oxidative stress could be beneficial in AD treatment, attenuating Aβ-induced neurotoxicity and improve neurological outcomes in AD. The term inflammaging characterizes a widely accepted paradigm that aging is accompanied by a low-grade chronic up-regulation of certain pro-inflammatory responses in the absence of overt infection, and is a highly significant risk factor for both morbidity and mortality in the elderly.
“…Thus, it could be assumed that SCOP may alleviate contextual fear. On the other hand, the SCOP-injected group was the only one that presented a strong prolongation of grooming time, which might be a manifestation of increased stress and anxiety (Kalueff and Tuohimaa 2005 ; Sałat et al 2016 ). These data remain apparently inconsistent, i.e., SCOP in the same test reduced contextual fear measured as freezing behavior and enhanced self-grooming that is usually associated with stress.…”
Section: Discussionmentioning
confidence: 99%
“…These valuable research tools enable to study various types of memory (Fig. 1 ) (Blaser and Heyser 2015 ; Cho et al 1999 ; Frankland et al 1998 ; Malikowska et al 2017 ; Podkowa et al 2016 ; Sałat et al 2016 ; Stiedl et al 2000 ; Sunyer et al 2007 ). Fig.…”
Nowadays cognitive impairments are a growing unresolved medical issue which may accompany many diseases and therapies, furthermore, numerous researchers investigate various neurobiological aspects of human memory to find possible ways to improve it. Until any other method is discovered, in vivo studies remain the only available tool for memory evaluation. At first, researchers need to choose a model of amnesia which may strongly influence observed results. Thereby a deeper insight into a model itself may increase the quality and reliability of results. The most common method to impair memory in rodents is the pretreatment with drugs that disrupt learning and memory. Taking this into consideration, we compared the activity of agents commonly used for this purpose. We investigated effects of phencyclidine (PCP), a non-competitive NMDA receptor antagonist, and scopolamine (SCOP), an antagonist of muscarinic receptors, on short-term spatial memory and classical fear conditioning in mice. PCP (3 mg/kg) and SCOP (1 mg/kg) were administrated intraperitoneally 30 min before behavioral paradigms. To assess the influence of PCP and SCOP on short-term spatial memory, the Barnes maze test in C57BL/J6 mice was used. Effects on classical conditioning were evaluated using contextual fear conditioning test. Additionally, spontaneous locomotor activity of mice was measured. These two tests were performed in CD-1 mice. Our study reports that both tested agents disturbed short-term spatial memory in the Barnes maze test, however, SCOP revealed a higher activity. Surprisingly, learning in contextual fear conditioning test was impaired only by SCOP.
Graphical Abstractᅟ
“…It is worth noting that although several studies used this measure of behavioral depression induced by pain, other reports showed that ambulatory locomotion in rodents did not decrease (or did so only minimally) in a variety of pain models such as CFA-induced inflammatory pain, prostatitis, ovariectomy-induced osteoporosis, diabetic neuropathy, or spared nerve injury, even in animals that displayed marked sensory hypersensitivity (e.g. Urban et al, 2011;Tékus et al, 2014;Schwartz et al, 2015;Zhou et al, 2015;Sałat et al, 2016;Montilla-García et al, 2017;Suzuki et al, 2018). The quantification of vertical activity may be more sensitive than ambulatory locomotion in detecting pain-induced alterations, in particular in pain models affecting the hindlimbs; this is exemplified in studies of monoiodoacetate-induced osteoarthritis or plantar incision (e.g.…”
Section: Pain Interference In Exploratory Locomotion In a Novel Envirmentioning
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