Mitochondrial activity in different regions of the brain at the onset of streptozotocin-induced diabetes in rats

Abstract

Diabetes affects a variety of tissues including the central nervous system; moreover, some evidence indicates that memory and learning processes are disrupted. Also, oxidative stress triggers alterations in different tissues including the brain. Recent studies indicate mitochondria dysfunction is a pivotal factor for neuron damage. Therefore, we studied mitochondrial activity in three brain regions at early type I-diabetes induction. Isolated mitochondria from normal hippocampus, cortex and cerebellum revealed different rates of oxygen consumption, but similar respiratory controls. Oxygen consumption in basal state 4 significantly increased in the mitochondria from all three brain regions from diabetic rats. No relevant differences were observed in the activity of respiratory complexes, but hippocampal mitochondrial membrane potential was reduced. However, ATP content, mitochondrial cytochrome c, and protein levels of β-tubulin III, synaptophysin, and glutamine synthase were similar in brain regions from normal and diabetic rats. In addition, no differences in total glutathione levels were observed between normal and diabetic rat brain regions. Our results indicated that different regions of the brain have specific metabolic responses. The changes in mitochondrial activity we observed at early diabetes induction did not appear to cause metabolic alterations, but they might appear at later stages. Longer-term streptozotocin treatment studies must be done to elucidate the impact of hyperglycemia in brain metabolism and the function of specific brain regions.

Insulin deficiency and intranasal insulin alter brain mitochondrial function: a potential factor for dementia in diabetes

“…Similar to muscle (9, 10), we observed impaired ATP production on insulin withdrawal in brain. However, previous reports in STZ-diabetic rats, without being maintained on insulin, reported no differences in brain ATP levels (34,35) unlike the reduction in ATP production in the current study. These discrepancies with the current study may stem from differences in species, the lack of insulin treatment in the previous studies, and the methodology to assess ATP production vs. content.…”

“…A Fluorolog 3 (Horiba Scientific, Piscataway, NJ, USA) spectrofluorometer was used to continuously measure the autofluorescence of NADPH. Ten microliters of isolated mitochondria suspension was added to a quartz cuvette with 2 ml of buffer Z containing (in millimolars) 110 K-MES, 35 KCl, 1 EGTA, 5 K 2 HPO 4 , 3 MgCl 2 -6H 2 O, and 5 mg/ml bovine serum albumin (pH 7.4, 295 mOsm) and 2.5 mM D-Glucose. The same stepwise titration protocol was used to induce states 1, 2, 3, and 4 as previously described.…”

Neuroprotective effects of mango cv. ‘Ataulfo’ peel and pulp against oxidative stress in streptozotocin‐induced diabetic rats

“…Diets were isocaloric (3.5 kcal g −1 ); 57% of kcal from carbohydrates, 29% protein and 14% from lipids. Ingredients [1][2][3][4][5] were obtained from Bio-Serv (Flemington, NJ, USA) #3200 1 ; #1100 2 ; #F800 3 ; #F8505 4 ; #6105 5 ; Ingredient 6 were obtained as described in the current paper.…”

“…1 These molecular and structural changes are associated with motor neuron dysfunction and impaired cognition in streptozotocin (STZ)induced diabetic rats. 2 It is therefore essential to search for active bioactive molecules that could prevent or counteract oxidative damage in these specific brain regions.…”

“…Purkinje and granular cells in the cerebral cortex have been reported to be distorted and morphologically altered in untreated diabetic rats, due to their vulnerability to oxidative stress 1 . These molecular and structural changes are associated with motor neuron dysfunction and impaired cognition in streptozotocin (STZ)‐induced diabetic rats 2 . It is therefore essential to search for active bioactive molecules that could prevent or counteract oxidative damage in these specific brain regions.…”