Fábio Caldana

Reversal of age-related deficits in object recognition memory in rats with l-deprenyl.

The monoamine-oxidase-B (MAO-B) inhibitor l-deprenyl (selegiline) is effective in treating Parkinsons disease and possibly cognitive deficits associated with aging, Alzheimers disease and HIV dementia. The aim of the present study was to investigate the effects of l-deprenyl on short- and long-term recognition memory in aged rats. Young adult and aged male Wistar rats were trained in a novel object recognition task. Retention test trials were carried out at 1.5 or 24 h after training. Aged rats showed impaired recognition memory retention 24 h after training when compared to young animals. Treatment with a daily systemic injection of l-deprenyl (1.0 mg/kg) for 21 days reversed the memory impairment. A control experiment indicated that l-deprenyl did not affect sensorimotor functions. The results suggest that l-deprenyl reverses age-related deficits in long-term recognition memory.

Haloperidol- and clozapine-induced oxidative stress in the rat brain.

Haloperidol (HAL) is a typical neuroleptic that acts primarily as a D2 dopamine receptor antagonist. It has been proposed that reactive oxygen species play a causative role in neurotoxic effects induced by HAL. Adult male Wistar rats received daily injections of HAL (1.5 mg/kg) or clozapine (CLO, 25 mg/kg), an atypical neuroleptic, for 28 days. Control animals were given saline (SAL; NaCl 0.9%). Oxidative parameters in the brain were measured in the striatum (ST), hippocampus (HP) and cortex (CX). Thiobarbituric acid (TBA) reactive substances (TBAR) levels were increased by HAL treatment in the ST and decreased in CX of both of the HAL- and CLO-treated rats. Protein carbonyls were significantly increased by both HAL and CLO in the HP. The nonenzymatic antioxidant potential was decreased in the HP, and superoxide production was significantly increased in the ST following treatment with HAL. CLO induced an increase in superoxide production in the HP. Neither HAL nor CLO affected catalase (CAT) and superoxide dismutase (SOD) activities. The findings suggest that HAL and CLO can induce oxidative damage to the ST and HP in rats.

Selegiline protects against recognition memory impairment induced by neonatal iron treatment.

Excess of iron in the brain has been implicated in the pathogenesis of several human neurodegenerative diseases, for example Alzheimers disease and Parkinsons disease. It has been shown that the neonatal period is critical for the establishment of normal iron content in the adult brain. Moreover, it is known that aging alters the cerebral distribution of this metal. We have recently described that neonatal administration of iron severely impaired novel object recognition memory in rats. The aim of the present study was to determine whether selegiline, a monoamine oxidase (MAO) inhibitor known for its neuroprotective properties, could protect rats against cognitive impairment induced by neonatal administration of iron. In the first experiment, male Wistar rats received vehicle (5% sorbitol in water) or iron (10.0 mg/kg) orally from postnatal days 12 to 14 and saline (0.9% NaCl) or selegiline (1.0 or 10.0 mg/kg) intraperitoneally for 21 days, starting 24 h before the first iron dosing. In the second experiment, rats were given either vehicle or iron (10.0 mg/kg) orally from postnatal days 12 to 14 followed by saline or selegiline (1.0 or 10.0 mg/kg) intraperitoneally for 21 days, starting when rats reached adulthood (50th day after birth). Iron-treated rats given selegiline in both doses showed no deficits in recognition memory. Rats receiving iron but no selegiline presented memory deficits. This is the first study reporting the reversion of iron-induced memory impairment, supporting the view that our model can be considered as a useful tool in the search for new drugs with neuroprotective and/or memory enhancing properties.

Impairments of social behavior and memory after neonatal gastrin-releasing peptide receptor blockade in rats: Implications for an animal model of neurodevelopmental disorders

The gastrin-releasing peptide receptor (GRPR) has been implicated in central nervous system (CNS) diseases, including neurodevelopmental disorders associated with autism. In the present study we examined the effects of GRPR blockade during the neonatal period on behavioral measures relevant to animal models of neurodevelopmental disorders. Male Wistar rats were given an intraperitoneal (i.p.) injection of either saline (SAL) or the GRPR antagonist [D-Tpi(6), Leu(13) psi(CH(2)NH)-Leu(14)] bombesin (6-14) (RC-3095; 1 or 10mg/kg) twice daily for 10days from postnatal days (PN) 1 to 10. Animals treated with RC-3095 showed pronounced deficits in social interaction when tested at PN 30-35 and impaired 24-h retention of memory for both novel object recognition (NOR) and inhibitory avoidance (IA) tasks tested at PN 60-71. Neither short-term memory tested 1.5h posttraining nor open field behavior were affected by neonatal GRPR blockade. The implications of the findings for animal models of neurodevelopmental disorders are discussed.

Efeito de estratégias de codificação sobre a memória contextual em idosos

Previous researches suggest that contextual memory is especially susceptible to the negative effects of aging upon cognition. The purpose of this study was to evaluate the effects of memorization strategies on the performance of twenty-four elders and twenty-one young participants on contextual memory task. Within each of the age groups, the participants were divided into those that received or did not receive specific orientation to link objects to a context. At test session, participants were engaged in object and context recognition tests. Findings showed that the specific orientation to link object to context was able to revert the contextual memory deficits of the elders.