Preserved LTP and water maze learning in hyperglycaemic–hyperinsulinemic ZDF rats

Belanger, Anne-Marie; Lavoie, Nathalie; Trudeau, François; Massicotte, Guy; Gagnon, Sylvain

doi:10.1016/j.physbeh.2004.08.031

Cited by 51 publications

(47 citation statements)

References 45 publications

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“…Analyses of behavioral performance and hippocampal synaptic plasticity in experimental models of type 2 diabetes have also yielded inconsistent findings, with some studies suggesting that water maze performance and hippocampal LTP are reduced [28], while others report that these measures are unaffected [29]. One important caveat associated with these studies is that performance in the water maze is dependent upon loco-motor activity, which may be adversely affected in diabetic animals that display decreases in muscle mass (such as type 1 models) or increases in adiposity (such as type 2 models).…”

Section: Insulin Receptor Expression and Signaling: Correlation With mentioning

confidence: 99%

Insulin signaling effects on memory and mood

Reagan¹

2007

Current Opinion in Pharmacology

109

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The escalating obesity/diabetes epidemic is an important health care issue that has critical socioeconomic ramifications. The complications of diabetes/obesity phenotypes extend to the central nervous system, including the hippocampus, a brain region that is particularly vulnerable to hyperglycemia and insulin resistance. Deficits in hippocampal synaptic plasticity observed in diabetes ultimately have deleterious consequences upon cognitive function. For example, recent studies using brain imaging technologies have identified cerebral atrophy in diabetic patients, suggesting that the neuroanatomical changes observed in experimental models of diabetes may accurately reflect what is occurring in the clinical setting. Deficits in insulin receptor signaling and impairments in hypothalamic-pituitary-adrenal (HPA) axis function also contribute to the neurological complications of diabetes phenotypes. The pathophysiological similarities between diabetes and stress-related mood disorders suggest that common mechanistic mediators may be involved in the etiology and progression of the neurological complications of these disorders. When combined with the accumulating evidence from pre-clinical models, these data support the hypothesis that a long-term consequence of diabetes/obesity phenotypes is accelerated brain aging that results in neuropsychological deficits and increased vulnerability to co-morbidities such as depressive illness.

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Section: Insulin Receptor Expression and Signaling: Correlation With mentioning

confidence: 99%

Insulin signaling effects on memory and mood

Reagan¹

2007

Current Opinion in Pharmacology

109

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“…51 The integrity of synaptic function was also preserved in ZDF rats as no alterations in long-term potentiation were observed in the CA1 area of the hippocampus. The authors came to the conclusion that the resistance of ZDF rats to cognitive dysfunctions might be related to the protective action of moderate hyperinsulinemia typical of this model, and also with a short duration of DM.…”

Section: Discussionmentioning

confidence: 92%

“…These include mutant GK and ZDF rats with obesity, insulin resistance and mild hyperglycemia, KKAy mice with hyperinsulinemia, impaired glucose tolerance and increased oxidative stress, and also rats with symptoms of T2DM induced by HFD and treated with low doses of STZ. [5][6][7][8][51][52][53] Some authors failed to detect the changes in the cognitive functions of the animals with obesity and T2DM, while on the contrary, others reported considerable impairment of behavior, learning and memory.…”

Section: Discussionmentioning

confidence: 99%

A positive effect of intranasal insulin on spatial memory in rats with neonatal diabetes mellitus

et al. 2011

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Type 2 diabetes mellitus (T2DM) is associated with cognitive impairments. However, their causal factors and the approaches to be used in their treatment have not been fully clarified and further study is needed. The aim of this work was to study the effect of intranasal insulin (I-I) on cognitive functions in rats with experimental T2DM. Neonatal rats (5 days old) were treated with an intraperitoneal (i.p.) administration of a single dose of streptozotocin (STZ) (80 mg/kg i.p.) which in adult animals leads to impairment of glucose tolerance and mild hyperglycemia, typical of T2DM. The insulin receptor binding in the synaptosomal and liver membranes was evaluated with [ 125 I]-insulin, and the insulin receptor substrate 2 (IRS2) expression in the brain was estimated by RT-PCR. Daily I-I (0.48 IU/day) or placebo were delivered to diabetic and non-diabetic rats during a week before and the 39 days of cognition experiments. Spatial memory and learning were studied in a Morris water-maze (MWM) test. The MWM test showed that, in the case of diabetic rats, the latent period for finding the platform (escape latency) and the swimming path length were increased, and the number of annulus crossings decreased compared with control (P<0.05). I-I normalized cognitive functions in diabetic rats but had no effect on those of non-diabetic animals. Specific insulin binding in the liver of diabetic rats was decreased, indicating peripheral insulin resistance, but changed very little in the brain. In the hypothalamus of diabetic rats, but not in the cortex and the olfactory bulbs, the expression of IRS2 was reduced by 68% compared with control and was restored after I-I delivery. Rats with neonatal T2DM had cognitive deficit likely associated with impaired IRS2-mediated signaling pathways in the diabetic brain and eliminated by I-I treatment.

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“…119 For example, Bélanger and colleagues suggested that the absence of cognitive and electrophysiological dysfunctions in ZDF rats (a T2DM model), might be due to protective action of hyperinsulinemia. 118 However, there is conflicting information on its putative role as antioxidant.…”

Section: Insulin: a Putative Antioxidantmentioning

confidence: 99%

“…118 However, there is conflicting information on its putative role as antioxidant. 119 In fact, it was proposed that insulin per se or its signaling pathways can protect neurons against oxidative stressinduced apoptosis through Akt activation or GSK-3β inhibition. 34 On the other hand, it was suggested that insulin has a dose-dependent dual role: (1) at low doses, it has anti-inflammatory effects during short-term inflammatory provocation, and (2) during chronic hyperinsulinemia or inflammation, it may exacerbate inflammatory responses and increase oxidative stress markers.…”

Section: Insulin: a Putative Antioxidantmentioning

confidence: 99%

Diabetic encephalopathy: the role of oxidative stress and inflammation in type 2 diabetes

Soares¹,

Nunes²,

Reis³

et al. 2012

IJICMR

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Type 2 diabetes mellitus (T2DM) is a heterogeneous metabolic disorder associated with an increased risk for central nervous system disorders. Diabetic encephalopathy is a relatively unknown diabetes complication, characterized by electrophysiological, structural, neurochemical, and degenerative neuronal changes that lead to cognitive functioning limitations. Besides chronic hyperglycemia and dyslipidemia, diabetic encephalopathy represents the most relevant risk factor for cognitive dysfunction, increased incidence of dementia, and consequently Alzheimer´s disease (AD), also referred to as "type 3 diabetes." There has been recent evidence suggesting that oxidative stress and inflammation are key pathogenic factors for T2DM, cognitive decline, and neurodegenerative diseases, including AD. Thus in this review we aim to ascertain brain mechanisms underlying the link between T2DM and AD with a focus on oxidative stress and inflammatory processes. We also intend to review the main antioxidant/anti-inflammatory therapeutic strategies targeting the brain and contributing to halt the progression from diabetic encephalopathy into AD.

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Preserved LTP and water maze learning in hyperglycaemic–hyperinsulinemic ZDF rats

Cited by 51 publications

References 45 publications

Insulin signaling effects on memory and mood

Insulin signaling effects on memory and mood

A positive effect of intranasal insulin on spatial memory in rats with neonatal diabetes mellitus

Diabetic encephalopathy: the role of oxidative stress and inflammation in type 2 diabetes

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