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Neurosci Lett. 2013 Aug 9;549:82-6. doi: 10.1016/j.neulet.2013.06.021. Epub 2013 Jun 24.

Reduced numbers of cortical GABA-immunoreactive neurons in the chronic D-galactose treatment model of brain aging.

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  • 1Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China.


Chronic administration of d-galactose (d-gal) is widely used to mimic the process of brain aging; however, the neural mechanisms are still poorly understood. In this study, we investigated the effect of long-term d-gal treatment on the number of GABA-immunoreactive neurons in rat cerebral cortex and the behavioral correlates. After eight weeks of daily subcutaneous injection of d-gal (100mg/ml/kg), rats showed reduced exploratory activity and lower ambulation in the open field compared to controls. There was no significant reduction in total neurons in the cortex, but there was a marked decrease in the number of GABA-immunoreactive neurons in all cortical layers of d-gal-treated rats. The ratio of GABA-immunoreactive neurons to total neurons was significantly lower in all cortical layers of d-gal-treated rats, with greatest reductions in output layers III (39.9% reduction), V (46.3%), and VI (48.4%). Our study provides the first evidence that chronic d-gal treatment may decrease cortical GABAergic neurotransmission, especially in cerebral output layers. The reduction in GABA-immunoreactive cell number likely disrupts the intracortical excitatory/inhibitory balance and may contribute to the behavioral deficits observed in this aging model.

Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.


Cerebral cortex; Rat; d-Galactose; γ-Aminobutyric acid

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