Cognitive and motor perturbations in elderly with longstanding diabetes mellitus

Díaz-Gerevini, Gustavo Tomás; Repossi, G; Daín, Alejandro; Tarrés, María Cristina; Das, Undurti N.; Eynard, Aldo R.

doi:10.1016/j.nut.2013.11.007

Cited by 23 publications

(30 citation statements)

References 113 publications

(143 reference statements)

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“…Analyses revealed that those with high levels of both pro-inflammatory agents throughout the duration of the study, or increasing levels of IL-6 throughout the study, were at greater risk of cognitive impairment (Wichmann, Cruickshanks et al 2014). Similar results have been reported in patients with type 2 diabetic encephalopathy (Diaz-Gerevini, Repossi et al 2014) and with Alzheimer’s disease (Bettcher and Kramer 2014). …”

Section: The Hiv-1tg Rat As a Model Of Neurohivsupporting

confidence: 88%

The HIV-1 transgenic rat model of neuroHIV

Vigorito

Connaghan

Chang

2015

Brain, Behavior, and Immunity

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Despite the ability of current combination anti-retroviral therapy (cART) to limit the progression of HIV-1 to AIDS, HIV-positive individuals continue to experience neuroHIV in the form of HIV-associated neurological disorders (HAND), which can range from subtle to substantial neurocognitive impairment. NeuroHIV may also influence substance use, abuse, and dependence in HIV-positive individuals. Because of the nature of the virus, variables such as mental health co-morbidities make it difficult to study the interaction between HIV and substance abuse in human populations. Several rodent models have been developed in an attempt to study the transmission and pathogenesis of the HIV-1 virus. The HIV-1 transgenic (HIV-1Tg) rat is a reliable model of neuroHIV because it mimics the condition of HIV-infected patients on cART. Research using this model supports the hypothesis that the presence of HIV-1 viral proteins in the central nervous system increases the sensitivity and susceptibility of HIV-positive individuals to substance abuse.

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Section: The Hiv-1tg Rat As a Model Of Neurohivsupporting

confidence: 88%

The HIV-1 transgenic rat model of neuroHIV

Vigorito

Connaghan

Chang

2015

Brain, Behavior, and Immunity

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“…An association between peripheral inflammation and mild cognitive impairment is also present in other diseases leading to chronic inflammation as diabetes, rheumatoid arthritis, obesity or chronic kidney disease (Umemura et al, 2011; Shin et al, 2013; da Matta et al, 2014; Díaz-Gerevini et al, 2014; Nguyen et al, 2014). To reduce peripheral inflammation patients with some of these diseases are being treated with compounds directed to inhibit TNF-a, which plays a pivotal role in the initiation and amplification of the inflammatory cascade (Cheng et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Reducing Peripheral Inflammation with Infliximab Reduces Neuroinflammation and Improves Cognition in Rats with Hepatic Encephalopathy

Dadsetan

Balzano

Forteza

et al. 2016

Front. Mol. Neurosci.

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Inflammation contributes to cognitive impairment in patients with hepatic encephalopathy (HE). However, the process by which peripheral inflammation results in cognitive impairment remains unclear. In animal models, neuroinflammation and altered neurotransmission mediate cognitive impairment. Taking into account these data, we hypothesized that in rats with HE: (1) peripheral inflammation is a main contributor to neuroinflammation; (2) neuroinflammation in hippocampus impairs spatial learning by altering AMPA and/or NMDA receptors membrane expression; (3) reducing peripheral inflammation with infliximab (anti-TNF-a) would improve spatial learning; (4) this would be associated with reduced neuroinflammation and normalization of the membrane expression of glutamate receptors. The aims of this work were to assess these hypotheses. We analyzed in rats with portacaval shunt (PCS) and control rats, treated or not with infliximab: (a) peripheral inflammation by measuring prostaglandin E2, IL10, IL-17, and IL-6; (b) neuroinflammation in hippocampus by analyzing microglial activation and the content of TNF-a and IL-1b; (c) AMPA and NMDA receptors membrane expression in hippocampus; and (d) spatial learning in the Radial and Morris water mazes. We assessed the effects of treatment with infliximab on peripheral inflammation, on neuroinflammation and AMPA and NMDA receptors membrane expression in hippocampus and on spatial learning and memory. PCS rats show increased serum prostaglandin E2, IL-17, and IL-6 and reduced IL-10 levels, indicating increased peripheral inflammation. PCS rats also show microglial activation and increased nuclear NF-kB and expression of TNF-a and IL-1b in hippocampus. This was associated with altered AMPA and NMDA receptors membrane expression in hippocampus and impaired spatial learning and memory in the radial and Morris water maze. Treatment with infliximab reduces peripheral inflammation in PCS rats, normalizing prostaglandin E2, IL-17, IL-6, and IL-10 levels in serum. Infliximab also prevents neuroinflammation, reduces microglial activation, translocates NF-kB into nucleoli and normalizes TNF-a and IL-1b content in hippocampus. This was associated with normalization of AMPA receptors membrane expression in hippocampus and of spatial learning and memory. The results suggest that peripheral inflammation contributes to spatial learning impairment in PCS rats. Treatment with anti-TNF-a could be a new therapeutic approach to improve cognitive function in patients with HE.

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“…Epidemiologic studies suggest that diabetes mellitus (DM), a complex metabolic disorder, is a risk factor for cognitive decline . Long‐term diabetes‐induced cognitive decline is characterized by neuropathological alterations including synapse loss, neuronal apoptosis, tau phosphorylation and advanced glycation end products (AGEs) .…”

Section: Introductionmentioning

confidence: 99%

“…Long‐term diabetes‐induced cognitive decline is characterized by neuropathological alterations including synapse loss, neuronal apoptosis, tau phosphorylation and advanced glycation end products (AGEs) . Recently, there has been an increasing interest in the notion that activated innate immunity is the critical pathogeneses of diabetes‐related cognitive disorder . However, the detailed mechanisms of innate immunity activation in diabetic CNS are still ill‐understood.…”

Section: Introductionmentioning

confidence: 99%

“…Epidemiologic studies suggest that diabetes mellitus (DM), a complex metabolic disorder, is a risk factor for cognitive decline. [1][2][3][4] Long-term diabetes-induced cognitive decline is characterized by neuropathological alterations including synapse loss, neuronal apoptosis, tau phosphorylation and advanced glycation end products (AGEs). [5][6][7][8] Recently, there has been an increasing interest in the notion that activated innate immunity is the critical pathogeneses of diabetesrelated cognitive disorder.…”

Section: Introductionmentioning

confidence: 99%

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High glucose‐induced complement component 3 up‐regulation via RAGE‐p38MAPK‐NF‐κB signalling in astrocytes: In vivo and in vitro studies

Zhao

Luo

Chen

et al. 2018

J Cellular Molecular Medi

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Diabetes is considered as a risk for cognitive decline, which is characterized by neurodegenerative alteration and innate immunity activation. Recently, complement 3 (C3), the critical central component of complement system, has been reported to play a key role in neurodegenerative alterations under pathological condition. Receptor for advanced glycation end products (RAGE) activation is confirmed to mediate several inflammatory cytokines production. However, whether C3 activation participates in the diabetic neuropathology and whether this process is regulated by RAGE activation remains unknown. The present study aimed to investigate the role of C3 in streptozotocin‐induced diabetic mice and high glucose‐induced primary astrocytes and the underlying modulatory mechanisms. The decreased synaptophysin density and increased C3 deposition at synapses were observed in the diabetic brain compared to the control brain. Furthermore, the elevated C3 was co‐localized with GFAP‐positive astrocytes in the diabetic brain slice in vivo and high glucose‐induced astrocytes culture in vitro. Diabetes/high glucose‐induced up‐regulation of C3 expression at gene, protein and secretion levels, which were attenuated by pre‐treatment with RAGE, p38MAPK and NF‐κB inhibitors separately. These results demonstrate that high glucose induces C3 up‐regulation via RAGE‐ p38MAPK‐NF‐κB signalling in vivo and in vitro, which might be associated with synaptic protein loss.

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Cognitive and motor perturbations in elderly with longstanding diabetes mellitus

Cited by 23 publications

References 113 publications

The HIV-1 transgenic rat model of neuroHIV

The HIV-1 transgenic rat model of neuroHIV

Reducing Peripheral Inflammation with Infliximab Reduces Neuroinflammation and Improves Cognition in Rats with Hepatic Encephalopathy

High glucose‐induced complement component 3 up‐regulation via RAGE‐p38MAPK‐NF‐κB signalling in astrocytes: In vivo and in vitro studies

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