Hyperglycemia not hypoglycemia alters neuronal dendrites and impairs spatial memory.
OBJECTIVE
We previously reported that chronic hyperglycemia, but not hypoglycemia, was associated with the reduction of neuronal size in the rat brain. We hypothesized that hyperglycemia-induced changes in neuronal structure would have negative consequences, such as impaired learning and memory. We therefore assessed the effects of hyperglycemia and hypoglycemia on neuronal dendritic structure and cognitive functioning in young rats.


METHODS
Experimental manipulations were conducted on male Wistar rats for 8 wk, beginning at 4 wk of age. At the completion of the treatments, all rats were trained in the radial-arm water maze, a spatial (hippocampus-dependent) learning and memory task. Three groups of rats were tested: an untreated control group, a streptozotocin-induced diabetic (STZ-D) group, and an intermittent hypoglycemic group. Following behavioral training, the brains of all animals were examined with histologic and biochemical measurements.


RESULTS
Peripheral hyperglycemia was associated with significant increases in brain sorbitol (7.5 +/- 1.6 vs. 5.84 +/- 1.0 microM/mg) and inositol (9.6 +/- 1.4 vs. 7.1 +/- 1.1 microM/mg) and reduced taurine (0.65 +/- 0.1 vs. 1.3 +/- 0.1 mg/mg). Histologic evaluation revealed neurons with reduced dendritic branching and spine density in STZ-D rats but not in control or hypoglycemic animals. In addition, the STZ-D group exhibited impaired performance on the water maze memory test.


CONCLUSIONS
Hyperglycemia, but not hypoglycemia, was associated with adverse effects on the brain polyol pathway activity, neuronal structural changes, and impaired long-term spatial memory. This finding suggests that the hyperglycemic component of diabetes mellitus has a greater adverse effect on brain functioning than does intermittent hypoglycemia.
Malone
John I
JI
Department of Pediatrics, University of South Florida College of Medicine, Tampa, FL, USA. jmalone@hsc.usf.edu
Hanna
Suzan
S
Saporta
Samuel
S
Mervis
Ronald F
RF
Park
Collin R
CR
Chong
Ling
L
Diamond
David M
DM
D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism; D003712:Dendrites / Q000473:pathology*; D049229:Dendritic Spines / Q000473:pathology / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006624:Hippocampus / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications* / Q000503:physiopathology; D007003:Hypoglycemia / Q000150:complications / Q000503:physiopathology; D007294:Inositol / Q000378:metabolism; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology*; D009474:Neurons / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013012:Sorbitol / Q000378:metabolism; D013037:Spatial Behavior / Q000502:physiology; D013654:Taurine / Q000378:metabolism
D013654:Taurine; D007294:Inositol; D013012:Sorbitol