Hyperglycemia Not Hypoglycemia Alters Neuronal Dendrites and Impairs Memory

It was previously reported that chronic hyperglycemia, and not hypoglycemia, was associated with the reduction of neuronal size in the rat brain. So it was 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.

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.

The results showed that peripheral hyperglycemia was associated with significant increases in brain sorbitol and inositol and reduced taurine. 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.

From the results it was concluded that, 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 has a greater adverse effect on brain functioning than does intermittent hypoglycemia.

Pediatr Diabetes. 2008 Dec;9(6):531-9.