Isoform-specific distribution of 14-3-3 proteins in the hippocampus of streptozotocin-induced diabetic rats

Diabetes mellitus is associated with cognitive deficits in humans and animal models. These deficits are paralleled by neurophysiological and structural changes in the central nervous system, particularly in the hippocampus, which plays an important role in memory formation. We previously reported that the magnitude of long-term potentiation at hippocampal Schaffer collateral-CA1 synapses was significantly impaired in streptozotocin (STZ)-induced type 1 diabetic rats (STZ rats). The present study investigated the mechanisms underlying morphological changes in the hippocampus of STZ rats. We performed a proteomic analysis of the hippocampus of STZ rats using two-dimensional gel electrophoresis followed by mass spectrometry. The distribution of 14-3-3 proteins identified by the proteomic analysis was then examined using immunohistochemistry. The results obtained revealed that 14-3-3 eta immunoreactivity in the dorsal hippocampus was weaker in STZ rats than in agematched control rats. Moreover, the density of glial fibrillary acidic protein-immunoreactive astrocytes in the dorsal hippocampus of STZ rats was increased, whereas 14-3-3 eta immunoreactivity in astrocytes and neurons in the dentate gyrus was significantly decreased. These results suggest that changes in 14-3-3 eta expression are involved in hippocampal astrogliosis or/and neurogenesis in STZ rats.