Cysteamine-induced acceleration of a senescent glial phenotype : effects on cognition and locomotion

Granule-laden astroglia accumulate with normal aging in several brain regions. Chronic treatment with cysteamine (CSH), a drug which depletes somatostatin (SS), produces accelerated astorcytic granule accumulation in rat hippocampus homologous to that observed in the aging brain. Behavioral tests performed following CSH administration have always been done with CSH present in the animals' systems and have shown cognitive deficits and decreases in locomotor activity, both of which have been attributed to the depletion of SS by CSH. Since chronic CSH exposure will also produce neuropathological changes in hippocampal astrocytes, we tested animals' spatial learning/memory and motor functioning at two time points following a chronic CSH treatment: (1) during CSH treatment to assess the effects of the drug itself, and (2) well after cessation of the drug to test the behavioral effects possibly associated with astrocytic neuropathology, not drug. A tendency toward a cognitive impairment was evident when rats were tested in a water maze 1 month following prolonged CSH treatment, but not during CSH exposure. On the other hand, when tested in locomotor activity boxes, only the animals tested during CSH treatment, not post-treatment, displayed a significant decrease in locomotion. Moreover, five weeks following CSH exposure, CSH-treated animals showed a significant increase in both the number of hippocampal astrocytic granules and SS levels; elevated SS concentration in the hippocampus is unlikely responsible for the seemingly detrimental effects of CSH on cognitive behavior since SS is antiamnesic. Taken together, these results suggest that CSH-induced cognitive deficits previously measured when CSH is in the animals' system may be influenced by concurrent locomotor deficits, and that CSH-induced astrocytic pathology may possibly be associated with a trend towards a deficit in cognition which is separate from the locomotor effects caused by the drug