Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study

Abstract

It is becoming increasingly clear that the brain is another site of diabetic end-organ damage [1]. Some diabetic patients develop cognitive deficits, which are generally moderate in young adults [2] but can be more pronounced in the elderly [3]. Recent epidemiological studies even report an association between diabetes and dementia [3,4]. Given the prevalence of diabetes among the elderly and the effect of cognitive impairment and dementia on the quality of life of patients and health care resources, a better understanding of the effects of diabetes on the brain is needed.Experimentally diabetic rodents develop cerebral deficits similar to those observed in diabetic patients. Streptozotocin (STZ)-diabetic rats have been found to have impaired learning and memory functions [5] and increases in the peak latencies of brainstem audi- Diabetologia (2001) Abstract Aims/hypothesis. It is increasingly evident that the brain is another site of diabetic end-organ damage. The pathogenesis has not been fully explained, but seems to involve an interplay between aberrant glucose metabolism and vascular changes. Vascular changes, such as deficits in cerebral blood flow, could compromise cerebral energy metabolism. We therefore examined cerebral metabolism in streptozotocin-diabetic rats in vivo by means of localised 31 P and 1 H magnetic resonance spectroscopy. Methods. Rats were examined 2 weeks and 4 and 8 months after diabetes induction. A non-diabetic group was examined at baseline and after 8 months.Results. In 31 P spectra the phosphocreatine:ATP, phosphocreatine:inorganic phosphate and ATP:inorganic phosphate ratios and intracellular pH in diabetic rats were similar to controls at all time points. In 1 H spectra a lactate resonance was detected as frequently in controls as in diabetic rats. Compared with baseline and 8-month controls 1 H spectra did, however, show a statistically significant decrease in N-acetylaspartate:total creatine (±14 % and ±23 %) and Nacetylaspartate:choline (±21 % and ±17 %) ratios after 2 weeks and 8 months of diabetes, respectively. Conclusion/interpretation. No statistically significant alterations in cerebral energy metabolism were observed after up to 8 months of streptozotocin-diabetes. These findings indicate that cerebral blood flow disturbances in diabetic rats do not compromise the energy status of the brain to a level detectable by magnetic resonance spectroscopy. Reductions in Nacetylaspartate levels in the brain of STZ-diabetic rats were shown by 1 H spectroscopy, which could present a marker for early metabolic or functional abnormalities in cerebral neurones in diabetes. [Diabetologia (2001) 44: 346±353]

Region-Specific Cerebral Metabolic Alterations in Streptozotocin-Induced Type 1 Diabetic Rats: An in vivo Proton Magnetic Resonance Spectroscopy Study

“…Early Metabolic Alterations at 4 Days Although there are a few previous in vivo 1 H-MRS studies that have investigated cerebral metabolic abnormalities in animal models of STZ-induced T1DM, [8][9][10]12 few of them measured metabolic changes in brain regions other than the hippocampus, nor at the time points earlier than 2 weeks after induction. In this study, we found that, under the hyperglycemia state, the STZtreated animals had significantly reduced tNAA/NAA levels in the striatum and hippocampus already at 4 days after induction.…”

Metabolite Differences in the Lenticular Nucleus in Type 2 Diabetes Mellitus Shown by Proton MR Spectroscopy

“…[3][4][5] Most studies suggest that diabetes affects either the number or the function of central neurons, which is mirrored by a reduction in NAA levels and a lower NAA/Cr ratio. [4][5][6] Studies investigating the effects of diabetes on Cho metabolism have produced inconsistent results. Studies by Kreis and Ross 5 and Biessels et al 6 reported no difference in Cho/Cr ratios in diabetic rats or in brain tissue from patients with diabetes.…”

“…[4][5][6] Studies investigating the effects of diabetes on Cho metabolism have produced inconsistent results. Studies by Kreis and Ross 5 and Biessels et al 6 reported no difference in Cho/Cr ratios in diabetic rats or in brain tissue from patients with diabetes. However, Sahin et al 7 found evidence of a lower Cho/Cr ratio in the parietal and frontal lobe white matter in patients with T2DM, which was inversely related to HbA1c levels.…”

Zinc deficiency and oxidative stress in brain: Magnetic resonance investigations in weanling rats

“…Our results, which imply decreased NAA levels, are consistent with those studying other neurological diseases, in either experimental animal models or humans, with associated neuronal damage. In a neurological study of streptozotocin-induced diabetic rats Biessels and coworkers [30] showed a decrease in both NAA/Cho and NAA/total Cr ratios 8 months after streptozotocin treatment. It was also found that cerebral NAA/Cr ratios were diffusely decreased in multiple sclerosis patients with early disease, a low demyelinating lesion load, and no significant disability [31].…”