Paloma Vicens

Effects of oral aluminum exposure on behavior and neurogenesis in a transgenic mouse model of Alzheimer's disease

The effects of a very low oral dose of Al on spatial learning and neurogenesis were evaluated in a transgenic mouse (Tg 2576) model of Alzheimer disease. At 5 months of age, wild and Tg 2576 mice received a diet supplemented with Al lactate at 0 and 1 mg/g of diet for 120 days. The experimental groups (n=7-8) were: control wild, Al-treated wild, control transgenic, and Al-treated transgenic. After 3 months of Al exposure, activity in an open-field and learning in a water maze were evaluated. At the end of the behavioral testing, in order to study cell proliferation and differentiation in the hippocampus, mice were injected with 5-bromo-2-deoxyuridine (BrdU) and sacrificed 1 or 28 days after the last BrdU injection. Tg 2576 mice were impaired in both acquisition and retention of the water maze task, showing higher amounts of beta-amyloid fragments in brain. Aluminum exposure impaired learning and memory in wild mice and increased the total number of proliferating cells in the dentate gyrus of hippocampus. The low Al doses here experimented suggest that this element might impair cognition in the general population at doses comparable to current levels of human exposure. Although these doses are not enough to interact with the amyloidogenic pathway, an increase in cell proliferation can indicate a reactive response of the brain to Al insult. Further investigations should be performed to corroborate the effects observed at very low doses of Al and to study the potential effects derived from a longer exposure period.

Impaired Spatial Learning and Unaltered Neurogenesis in a Transgenic Model of Alzheimers Disease After Oral Aluminum Exposure

Although it is well established that aluminum (Al) is neurotoxic, the potential role of this element in the etiology of Alzheimers disease (AD) is not well established. In this study, we evaluated the effects of oral Al exposure on spatial learning, memory and neurogenesis in Tg2576 mice, an animal model of AD in which Abeta plaques start to be deposited at 9 months of age. Aluminum was given as Al lactate (11 mg/g of food) for 6 months. At 11 months of age a water maze test was carried out to evaluate learning and memory. Subsequently, mice were injected with bromo-deoxyuridine (BrdU) and sacrificed 24 hours or 28 days after the last injection in order to assess proliferation, survival and differentiation of neurons. We observed impaired acquisition in the water maze task in Al-treated Tg2576 mice, as well as worse memory in the Al-exposed groups. In terms of neurogenesis, no effects of aluminum were observed in proliferation, survival and differentiation. The results of this investigation suggest that Tg2576 mice fed for 210 days with rodent chow supplemented with Al lactate at 11 mg/g of food have impaired spatial learning although their neurogenesis remains unmodified.

Behavioral effects of PNU-282987, an alpha7 nicotinic receptor agonist, in mice

The cholinergic system is closely related to learning and memory processes, and its neurodegeneration seems to be involved in neurodegenerative and neuropsychiatric cognitive disorders in the elderly. Alpha7 nicotinic acetylcholine receptors (nAChRs) have recently been shown to mediate neuroprotection and enhance cognitive performance in a variety of tasks, suggesting that there may be a new target for the pharmacotherapy of cognitive deficiencies. In this study, we investigated the behavioral effects of the acute and sub-chronic administration of 0, 1, 3, and 5 mg/kg of PNU-282987 (PNU) on motor activity, anxiety and learning in open-field and Morris water maze tasks in mice. Our results showed that the highest dose of PNU (5 mg/kg) diminished motor activity in the open-field following 5 and 12 days of administration (acute and sub-chronic, respectively). No effects on the acquisition of the Morris water maze were observed. However, only 1 mg/kg of PNU administered just before training trials over a period of 5 days showed beneficial effects on the retention of the water maze when evaluated 4 h after water maze acquisition. Further studies are needed to clarify the effects on the cognitive performance and potential neuroprotection of these agents in an elderly population with slight or severe deficiency in learning and memory processes, and/or in animal models vulnerable to neurodegenerative disorders.

Recognition memory and β-amyloid plaques in adult Tg2576 mice are not modified after oral exposure to aluminum.

The role of aluminum (Al) in Alzheimer disease is highly controversial. However, this element has been detected in neuritic plaques and neurofibrillary tangles in patients with Alzheimer disease. Its presence in neuritic plaques in hippocampus is especially relevant, as this is an area closely related to spatial learning and memory. In this study, the diet of wild-type and Tg2576 mice (animals overexpressing the human amyloid precursor protein) was supplemented with Al lactate (1 mg/g). General neurotoxic Al effects were evaluated using a functional observational battery and a novel object recognition task. Four experimental groups were used: Control-wild, Al-wild, Control-Tg, and Al-Tg mice. The results show a decreased home-cage activity and an increase in piloerection in all Al-exposed animals, and an increased sensorimotor reactivity in Tg2576 mice given Al. Neither Al treatment nor genotype had any noticeable effect on corticosterone levels and Al concentrations in frontal cortex and cerebellum of the mice. Recognition memory was impaired in Tg2576 mice, whereas &bgr;-amyloid plaque depositions were observed in all these animals. However, Al did not alter the recognition memory and &bgr;-amyloid plaque loads of Tg2576 mice.

Motor and anxiety effects of PNU-282987, an alpha7 nicotinic receptor agonist, and stress in an animal model of Alzheimer's disease.

Behavioral and Psychological Symptoms in Dementia (BPSD) are also seen in Alzheimers disease (AD), being agitation and anxiety common symptoms. Since cholinergic agonists used to be the first pharmacological intervention in AD and this neurotransmission system have been related to cognitive and behavioral symptoms in this serious disease, we here address the question of a possible therapeutic role of PNU-282987 (PNU), an alpha7 nicotinic agonist, in motor activity and anxiety-like behaviors in an animal model of AD. On the other hand, since stress is an unavoidable condition in our daily activities, which activates physiological systems and deregulates bodys homeostasis, we also evaluated the possible precipitating effects of stress in the onset of behavioral deficits in animals with susceptibility to AD. A dose of 0 or 1 mg/kg of PNU was administered to transgenic mice under restrained stress or not, resulting in 4 experimental groups: SAL, PNU, SAL-STR, PNU-STR. The main goal of this study was to evaluate the possible therapeutic role of PNU- 282987 alpha7 nicotinic agonist in motor activity and anxiety-like behaviors, as well as the possible effects of stress in precipitating the onset of behavioral deficits in animals with susceptibility to AD. The present results suggest a differential effect of stress (p=0.011) and PNU (p= 0.009) on anxiety evaluated in an open field depending on genetic vulnerability. Moreover, PNU seems to reverse stress effects in the same apparatus. This was also observed when a more sensitive task such as the zero maze was used.

Effects of an Alpha7 Nicotinic Receptor Agonist and Stress on Spatial Memory in an Animal Model of Alzheimer's Disease

The aim of the present study was to test the effects of PNU-282987 on spatial learning and memory and hippocampal neurogenesis in both intact and chronically stressed transgenic mice. Transgenic mice with susceptibility to Alzheimers disease (AD) under immobilization stress and not-stressed animals receiving 0 and 1 mg/kg of PNU-282987 (PNU) were evaluated in a water maze task. The effects of PNU and stress on proliferation of new cells in the hippocampus of these animals were also assessed. The latency to escape the platform was significantly higher in transgenic stressed mice compared to those in the wild stressed group, as well as in transgenic animals without PNU compared to control wild group. On retention of the task, differences emerged on stressed wild animals, PNU wild group, and stressed wild mice receiving PNU. However, no significant differences were detected on new cell proliferation. The results of the present study did not show any impact of stress in acquisition of a spatial task both in wild and transgenic mice. No clear effects of PNU on acquisition of a spatial task in transgenic mice with susceptibility to AD were detected. Although PNU and stress effects were detected on retention of the task in wild animals, no changes were noted in transgenic mice.

Behavioural effects of PNU‐282987 and stress in an animal model of Alzheimer's disease

Cholinergic deficits play an important role in both cognitive and behavioural alterations in Alzheimers disease. This study was aimed at evaluating the possible therapeutic role of PNU‐282987 (PNU), an α7 nicotinic cholinergic receptor agonist, and the possible effects of stress in precipitating the onset of behavioural deficits in animals with susceptibility to Alzheimers disease.

Estudio preliminar de la efectividad de la terapia asistida con perros en personas de la tercera edad

INTRODUCTION Animal-assisted therapy is increasingly present in several educational and health areas. The aim of this study is to assess the effectiveness of such interventions in the elderly population living in residential settings. MATERIALS AND METHODS A 12-week dog-assisted intervention program was designed, with 16 participants from a nursing home divided into an experimental group and a control group. RESULTS Several physical and psychological variables were assessed before and after the intervention. While there were no significant differences in the control group, the experimental group improved significantly after participating in the program. DISCUSSION The results support the hypothesis that animal-assisted interventions may be beneficial for residents in elderly care homes.