The CNS is one of the main organ systems that is affected in type 1 diabetes, as both cerebral glucose and insulin levels are frequently abnormal, even when the diabetes is well-controlled. Literature is emerging that documents pathophysiological CNS changes and neurocognitive deficits in both adults and children with type 1 diabetes, but empirical findings to date have often been inconsistent and difficult to interpret. This article provides a comprehensive review of current knowledge about the impact of type 1 diabetes on brain development and function, focusing particularly on the evidence for specific illness-related risk factors for CNS sequelae. We argue that clinical management of young patients with type 1 diabetes should take into account current knowledge of the relative risks of hypoglycemia and hyperglycemia to the developing brain.
"Numerous studies have shown that diabetic patients present a high risk of developing cognitive disorders , . Nowadays, diabetic encephalopathy is recognized as one of the most important complications of diabetes, which encompasses functional impairment of cognition, cerebral signal conduction, neurotransmission and synaptic plasticity, and underlying structural brain abnormalities , . "
[Show abstract][Hide abstract] ABSTRACT: Heterozygous Gigyf2+/- mice exhibits histopathological evidence of neurodegeneration such as motor dysfunction. Several lines of evidence have demonstrated the important role of insulin-like growth factor-1 receptor (IGF1R) signaling pathway in the neuropathogenic process of cognitive impairment, while decreased Grb10-Interacting GYF Protein 2 (GIGYF2) expression can alter IGF1R trafficking and its downstream signaling pathways. Growth factor receptor-bound protein 10 (Grb10), a suppressor of IGF1R pathway, has been shown to play a critical role in regulating diabetes-associated cognitive impairment. It remains unknown whether endogenous GIGYF2 expression contributes to the development of diabetes-associated cognitive impairment. Using streptozotocin (STZ)-induced diabetic mice model, we first demonstrated that a significantly increased level of GIGYF2 expression was correlated with a significant decrease in the expression of phosphorylated IGF1R as well as the phosphorylation of AKT and ERK1/2, two signaling pathways downstream of IGF1R, in the hippocampus of diabetic mice. On the contrary, in situ knockdown of GIGYF2 expression in hippocampus resulted in increased expression of phosphorylated IGF1R expression and correspondingly reversed the down-regulation of ERK1/2 phsophorylation but had no obvious effect on Grb10 expression. Functionally, knockdown of GIGYF2 expression markedly ameliorated diabetes-associated cognitive dysfunction as well as the ultrastructural pathology and abnormal neurobehavioral changes. These results suggest that increased expression of GIGYF2 might contribute to the development of diabetes-associated cognitive disorder via negatively regulating IGF1R signaling pathway. Therefore, down-regulation of GIGYF2 expression may provide a potential novel approach to treat diabetes-associated cognitive impairment caused by aberrant IGF1R signaling pathway.
PLoS ONE 09/2014; 9(9):e108559. DOI:10.1371/journal.pone.0108559 · 3.23 Impact Factor
"Such an expression is either low or absent in healthy brain (O'Keefe et al. 1999). Manifestations of diabetes related cellular changes in brain believed to cause reduced cognitive ability (Alvarez et al. 2009) and high susceptibility for dementia and Alzheimer disease (Biessels et al. 1994; Ristow, 2004; Northam et al. 2006). The degenerative changes in neurons (Suh et al. 2007) and declined neurogenesis (Choi et al. 2009; Alvarez et al. 2009) resulted in significant cognitive impairment. "
[Show abstract][Hide abstract] ABSTRACT: Diabetes Mellitus is associated with increased risk of cognitive and behavioural disorders with hitherto undeciphered role of glia. Glia as majority population in brain serve several vital functions, thus require pertinent revelation to further explicate the mechanisms affecting the brain function following diabetes. In this study we have evaluated glial changes in terms of phenotypic switching, proliferation and expression of activation cell surface markers and associated cellular degeneration in hippocampus following STZ-induced diabetes and caused cognitive impairments. Experimental diabetes was induced in Wistar rats by a single dose of STZ (45 mg/kg body weight; intraperitoneally) and changes were studied in 2nd, 4th and 6th week post diabetes confirmation using Barnes maze and T-maze test, immunohistochemistry and image analysis. An increase in GFAP expression sequentially from 2nd to 6th weeks of diabetes was analogous with the phenotypic changes and increased astrocyte number. Elevated level of S100β with defined stellate morphology further confirmed the astrocytosis following diabetes. Enhanced level of Iba-1 and MHC-II revealed the corroborated microglial activation and proliferation following diabetes, which was unresolved till date. Increased caspase-3 activity induced profound cell death upto 6th weeks post diabetes confirmation. Such caspase 3 mediated cellular damage with a concomitant activation of the astrocytes and microglia suggests that diabetes linked cell death activates the astrocytes and microglia in hippocampus which further underpin the progression and severity of brain disorders resulting in cognitive and behavioural impairments.
"Diabetes mellitus type 1 (DM1) is an endocrine disorder which is characterized by lack of insulin and hyperglycemia . For a long period, it was believed that the central nervous system (CNS) as an insulin independent organ is spared from diabetic complications; however, in recent decades, studies have provided evidence that indicates the deleterious effects of DM1 on structure and functions of the brain   . Although the mechanisms through which hyperglycemia might mediate these effects are not completely understood, it seems that hyperglycemia increases oxidative stress and free radicals generation. "
[Show abstract][Hide abstract] ABSTRACT: Background. Neuronal apoptosis is the major cause of diabetes central neuropathy, but its role in volumetric changes of hippocampus has not been clarified. The aims of this study were to assess the role of apoptosis in volumetric changes of dentate gyrus (DG) and CA3 region of hippocampus and to determine a reference point in which these neuropathological changes reach a meaningful level. Methods and Materials. Diabetes was induced in male Wistar rats () by streptozotocin (60 mg/kg). Six weeks after diabetes, verification animals were divided into four groups as follows: diabetic treated with insulin (3–5 U), diabetic treated with vitamin C (80 mg/kg), and diabetic and control groups. At the end of 8 weeks, numerical density of apoptotic neurons and volume of dentate gyrus and CA3 were calculated by stereological methods. Results. The number of apoptotic neurons in DG and CA3 in diabetic group showed significant level of difference in comparison with the control (). The volume of DG and CA3 in diabetic and vitamin C showed significant level of difference compared with control (). Conclusion. Our results suggest that DG and CA3 volume reduction begins and progresses independently of neuronal loss.
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