Neuroprotective effects of resistance physical exercise on the APP/PS1 mouse model of Alzheimer’s disease

IntroductionPhysical exercise has beneficial effects by providing neuroprotective and anti-inflammatory responses to AD. Most studies, however, have been conducted with aerobic exercises, and few have investigated the effects of other modalities that also show positive effects on AD, such as resistance exercise (RE). In addition to its benefits in developing muscle strength, balance and muscular endurance favoring improvements in the quality of life of the elderly, RE reduces amyloid load and local inflammation, promotes memory and cognitive improvements, and protects the cortex and hippocampus from the degeneration that occurs in AD. Similar to AD patients, double-transgenic APPswe/PS1dE9 (APP/PS1) mice exhibit Αβ plaques in the cortex and hippocampus, hyperlocomotion, memory deficits, and exacerbated inflammatory response. Therefore, the aim of this study was to investigate the effects of 4 weeks of RE intermittent training on the prevention and recovery from these AD-related neuropathological conditions in APP/PS1 mice.MethodsFor this purpose, 6-7-month-old male APP/PS1 transgenic mice and their littermates, negative for the mutations (CTRL), were distributed into three groups: CTRL, APP/PS1, APP/PS1+RE. RE training lasted four weeks and, at the end of the program, the animals were tested in the open field test for locomotor activity and in the object recognition test for recognition memory evaluation. The brains were collected for immunohistochemical analysis of Aβ plaques and microglia, and blood was collected for plasma corticosterone by ELISA assay.ResultsAPP/PS1 transgenic sedentary mice showed increased hippocampal Aβ plaques and higher plasma corticosterone levels, as well as hyperlocomotion and reduced central crossings in the open field test, compared to APP/PS1 exercised and control animals. The intermittent program of RE was able to recover the behavioral, corticosterone and Aβ alterations to the CTRL levels. In addition, the RE protocol increased the number of microglial cells in the hippocampus of APP/PS1 mice. Despite these alterations, no memory impairment was observed in APP/PS1 mice in the novel object recognition test.DiscussionAltogether, the present results suggest that RE plays a role in alleviating AD symptoms, and highlight the beneficial effects of RE training as a complementary treatment for AD

Modafinil induces rapid-onset behavioral sensitization and cross-sensitization with cocaine in mice: implications for the addictive potential of modafinil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)There is substantial controversy about the addictive potential of modafinil, a wake promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on arousal and cognition. The rapid-onset type of behavioral sensitization (i.e., a type of sensitization that develops within a few hours from the drug priming administration) has been emerged as a valuable tool to study binge-like patterns of drug abuse and the neuroplastic changes that occur quickly after drug administration that ultimately lead to drug abuse. Our aim was to investigate the possible development of rapid-onset behavioral sensitization to modafinil and bidirectional rapid-onset cross sensitization with cocaine in male Swiss mice. A priming injection of a high dose of modafinil (64 mg/kg) induced rapid-onset behavioral sensitization to challenge injections of modafinil at the doses of 16, 32, and 64 mg/kg, administered 4 h later. Furthermore, rapid-onset cross-sensitization was developed between modafinil and cocaine (64 mg/kg modafinil and 20 mg/kg cocaine), in a bidirectional way. These results were not due to residual levels of modafinil as the behavioral effects of the priming injection of modafinil were no longer present and modafinil plasma concentration was reduced at 4 h post-administration. Taken together, the present findings provide preclinical evidence that modafinil can be reinforcing per se and can enhance the reinforcing effects of stimulants like cocaine within hours after administration.There is substantial controversy about the addictive potential of modafinil, a wake promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on aro7FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)2014/24277-4sem informaçãosem informaçã

Aprendizagem de uma habilidade motora seriada em diferentes estágios de desenvolvimento

This study investigated the learning of a serial tracking task in different developmental stages. Fifteen children, fourteen adults and thirteen elderly practiced the task of tracking a sequence of six light stimuli for ten blocks of trial or until discover the sequence, during the stabilization phase, and two blocks of trial at the adaptation tests I and II. Performance was measured by the functional and non-functional responses and functional sequences. The results showed that adults were superior to the other participants, and elderly participants performed better than children only in the early practice, suggesting that the development stage interacts with the process of motor learning.Este estudo investigou a aprendizagem de uma tarefa motora seriada em diferentes estágios de desenvolvimento. Quinze crianças, 14 adultos e 13 idosos praticaram a tarefa de rastrear uma sequência de seis estímulos luminosos durante 10 blocos de tentativas ou até descobrir a sequência, constituindo a fase de estabilização e mais dois blocos de tentativas, referentes as fases de adaptação I e II. O desempenho foi mensurado por meio das respostas funcionais e não-funcionais e das sequências funcionais. Os resultados indicaram que os adultos foram superiores aos demais participantes, e idosos apresentaram melhor desempenho que crianças apenas no início da prática, sugerindo que o estágio de desenvolvimento interage com o processo de aprendizagem motora

Learning of a motor serial skill in different stages of development

Este estudo investigou a aprendizagem de uma tarefa motora seriada em diferentes estágios de desenvolvimento. Quinze crianças, 14 adultos e 13 idosos praticaram a tarefa de rastrear uma sequência de seis estímulos luminosos durante 10 blocos de tentativas ou até descobrir a sequência, constituindo a fase de estabilização e mais dois blocos de tentativas, referentes as fases de adaptação I e II. O desempenho foi mensurado por meio das respostas funcionais e não-funcionais e das sequências funcionais. Os resultados indicaram que os adultos foram superiores aos demais participantes, e idosos apresentaram melhor desempenho que crianças apenas no início da prática, sugerindo que o estágio de desenvolvimento interage com o processo de aprendizagem motora

Analysis of a Subacute Sclerosing Panencephalitis Genotype B3 Virus from the 2009-2010 South African Measles Epidemic Shows That Hyperfusogenic F Proteins Contribute to Measles Virus Infection in the Brain

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Measles Virus Bearing Measles Inclusion Body Encephalitis-Derived Fusion Protein Is Pathogenic after Infection via the Respiratory Route

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Modafinil Induces Rapid-Onset Behavioral Sensitization and Cross-Sensitization with Cocaine in Mice: Implications for the Addictive Potential of Modafinil

There is substantial controversy about the addictive potential of modafinil, a wake promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on arousal and cognition. The rapid-onset type of behavioral sensitization (i.e., a type of sensitization that develops within a few hours from the drug priming administration) has been emerged as a valuable tool to study binge-like patterns of drug abuse and the neuroplastic changes that occur quickly after drug administration that ultimately lead to drug abuse. Our aim was to investigate the possible development of rapid-onset behavioral sensitization to modafinil and bidirectional rapid-onset cross sensitization with cocaine in male Swiss mice. A priming injection of a high dose of modafinil (64 mg/kg) induced rapid-onset behavioral sensitization to challenge injections of modafinil at the doses of 16, 32, and 64 mg/kg, administered 4 h later. Furthermore, rapid-onset cross-sensitization was developed between modafinil and cocaine (64 mg/kg modafinil and 20 mg/kg cocaine), in a bidirectional way. These results were not due to residual levels of modafinil as the behavioral effects of the priming injection of modafinil were no longer present and modafinil plasma concentration was reduced at 4 h post-administration. Taken together, the present findings provide preclinical evidence that modafinil can be reinforcing per se and can enhance the reinforcing effects of stimulants like cocaine within hours after administration.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundo de Auxílio aos Docentes e Alunos (FADA)Associação Fundo de Incentivo à Psicofarmacologia (AFIP)Univ Fed Sao Paulo, Dept Physiol, Lab Neurophysiol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Psychobiol, Sao Paulo, BrazilUniv Estadual Campinas, Fac Pharmaceut Sci, Campinas, SP, BrazilLaboratory of Neurophysiology, Department of Physiology, Universidade Federal de São Paulo, São Paulo, BrazilDepartment of Pharmacology, Universidade Federal de São Paulo, São Paulo, BrazilDepartment of Psychobiology, Universidade Federal de São Paulo, São Paulo, BrazilFAPESP: 2014/24277-4Web of Scienc