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

Abstract

Clinical and experimental in vivo 1 H-magnetic resonance spectroscopy ( 1 H-MRS) studies have demonstrated that type 1 diabetes mellitus (T1DM) is associated with cerebral metabolic abnormalities. However, less is known whether T1DM induces different metabolic disturbances in different brain regions. In this study, in vivo 1 H-MRS was used to measure metabolic alterations in the visual cortex, striatum, and hippocampus of streptozotocin (STZ)-induced uncontrolled T1DM rats at 4 days and 4 weeks after induction. It was observed that altered neuronal metabolism occurred in STZ-treated rats as early as 4 days after induction. At 4 weeks, T1DM-related metabolic disturbances were clearly region specific. The diabetic visual cortex had more or less normalappearing metabolic profile; while the striatum and hippocampus showed similar abnormalities in neuronal metabolism involving N-acetyl aspartate and glutamate; but only the hippocampus exhibited significant changes in glial markers such as taurine and myo-inositol. It is concluded that cerebral metabolic perturbations in STZ-induced T1DM rats are region specific at 4 weeks after induction, perhaps as a manifestation of varied vulnerability among the brain regions to sustained hyperglycemia.

Metabolic profile of visual cortex in diabetic rats measured with in vivo proton MRS

“…T 2 ‐weighted images were acquired with a relaxation enhancement (RARE) sequence: repetition time ( T R ) = 4000 ms, echo time ( T E ) = 40 ms, number of averages (NA) = 2, field of view (FOV) = 3 cm × 3 cm, matrix size = 256 × 256, slice thickness = 0.5 mm. Localized 1 H spectra were acquired from visual cortex using a point‐resolved spectroscopy (PRESS) sequence with T R = 2500 ms, T E = 15 ms, spectral width = 4000 Hz, NA = 128, FOV = 1 mm × 4 mm × 4 mm . The LCModel software (LCModel Version 6.3‐1A; Stephen Provencher, Oakville, ON, Canada) was used to quantify the metabolite contents .…”

“…Localized 1 H spectra were acquired from visual cortex using a point‐resolved spectroscopy (PRESS) sequence with T R = 2500 ms, T E = 15 ms, spectral width = 4000 Hz, NA = 128, FOV = 1 mm × 4 mm × 4 mm . The LCModel software (LCModel Version 6.3‐1A; Stephen Provencher, Oakville, ON, Canada) was used to quantify the metabolite contents . No extra data processing steps were employed other than those incorporated inside LCModel.…”

“…A 72 mm diameter linear transmitter coil was used for excitation and a rat brain receive-only coil array for reception. [27][28][29] The LCModel software (LCModel Version 6.3-1A; Stephen Provencher, Oakville, ON, Canada) was used to quantify the metabolite contents. 28 No extra data processing steps were employed other than those incorporated inside LCModel.…”

Impact of Metabolic Diseases on Cerebral Circulation: Structural and Functional Consequences

“…8). It was also reported that STZ-mediated changes in cerebral perfusion and metabolism are region specific (261). A two-photon fluorescence microscopy study reported disturbed cerebral capillary blood flow in STZ-induced T1D mice increases the susceptibility to ischemic insults (123).…”

Regional metabolic differences in rat prefrontal cortex measured with in vivo 1H‐MRS correlate with regional histochemical differences

“…5 Regional metabolic variations have also been demonstrated in rodent brains, not only between the cerebral cortex and subcortical structures, but also among different cortical areas. [6][7][8] For example, it has been shown that, in mouse brain, the anterior cortex had significantly lower NAA, Gln, myo-inositol (Ins) and total creatine (tCr) levels than the posterior cortex, 7 and such differences were thought to be related to higher density of myelinated fibers and larger phospholipid synthesis in the posterior cortex. 7 The rodent PFC is comprised of multiple sub-regions with distinctive cytoarchitectures and functions, including prelimbic cortex (PrL), infralimbic cortex (IL) and CG.…”