RESUMO
Normal pressure hydrocephalus (NPH) compromises the morphology of the corpus callosum (CC). This study aims to determine whether 60- or 120-day NPH disrupts the cytoarchitecture and functioning of white matter (WM) and oligodendrocyte precursor cells (OPCs) and establish whether these changes are reversible after hydrocephalus treatment. NPH was induced in CD1 adult mice by inserting an obstructive lamina in the atrium of the aqueduct of Sylvius. Five groups were assembled: sham-operated controls (60 and 120 days), NPH groups (60 and 120 days), and the hydrocephalus-treated group (obstruction removal after 60-d hydrocephalus). We analyzed the cellular integrity of the CC by immunohistochemistry, TUNEL analysis, Western blot assays, and transmission electron microscopy (TEM). We found a reduction in the width of the CC at 60 and 120 days of NPH. TEM analysis demonstrated myelin abnormalities, degenerative changes in the WM, and an increase in the number of hyperdense (dark) axons that were associated with significant astrogliosis, and microglial reactivity. Hydrocephalus also caused a decrease in the expression of myelin-related proteins (MOG and CNPase) and reduced proliferation and population of OPCs, resulting in fewer mature oligodendrocytes. Hydrocephalus resolution only recovers the OPC proliferation and MOG protein density, but the rest of the WM abnormalities persisted. Interestingly, all these cellular and molecular anomalies occur in the absence of behavioral changes. The results suggest that NPH severely disrupts the myelin integrity and affects the OPC turnover in the CC. Remarkably, most of these deleterious events persist after hydrocephalus treatment, which suggests that a late treatment conveys irreversible changes in the WM of CC.
Assuntos
Hidrocefalia de Pressão Normal , Células Precursoras de Oligodendrócitos , Camundongos , Animais , Corpo Caloso , 2',3'-Nucleotídeo Cíclico Fosfodiesterases/genética , Bainha de Mielina , Oligodendroglia , Proteínas da Mielina , Proliferação de CélulasRESUMO
Inaccurate and distorted timing are associated with neurodegenerative disorders such as Alzheimer's disease and schizophrenia in humans, which generates interest in the discovery and understanding of the factors behind such timing difficulties. Timing research in mice has taken an important role, because the availability of genetically-altered strains allows establishing the causal role of specific genes on such neurodegenerative disorders. Nevertheless, few studies have considered mice's sex and some have found sex differences in timing, although results are not yet conclusive. We tested female and male CD1 mice, an outbred strain not yet studied in a peak procedure. By varying the percentage of peak trials and the presence of a gap and/or a distractor in the tests, we found no sex differences in accuracy, precision, or attention. Both females and males followed a stop-clock strategy after distractor and gap + distractor trials. This suggests that both male and female CD1 mice may be exposed to a peak procedure to study factors associated to neurotoxicology or neurogenesis.
Assuntos
Doença de Alzheimer , Atenção , Animais , Feminino , Masculino , Camundongos , Caracteres SexuaisRESUMO
Cyclohexane (CHX) is an organic solvent commonly used as a drug-of-abuse. This drug increases the oxidative stress and glial reactivity in the hippocampus, which suggests that this brain region is vulnerable to CHX effects. This study aimed to establish the behavioral changes and the pathological alterations that occur in the Cornu Ammonis 3 (CA3) and Dentate Gyrus (DG) after a long-lasting exposure to CHX. We exposed CD1 mice to a recreational-like dose of CHX (~ 30,000 ppm) for 30 days and explored its consequences in motor skills, reward-seeking behavior, and the CA3 and DG hippocampal subfields. Twenty-four hours after the last administration of CHX, we found a significant decrease in the number of c-Fos+ cells in the hippocampal CA3 and DG regions. This event coincided with an increased in NMDAR1 expression and apoptotic cells in the CA3 region. At day 13th without CHX, we found a persistent reduction in the number of c-Fos+ and TUNEL+ cells in DG. At both time points, the CHX-exposed mice showed a strong overexpression of neuropeptide Y (NPY) in the CA3 stratum lucidum and the hippocampal hilus. In parallel, we used an operant-based task to assess motor performance and operant conditioning learning. The behavioral analysis indicated that CHX did not modify the acquisition of operant conditioning tasks, but affected some motor skills and increased the reward-seeking behavior. Altogether, this evidence reveals that CHX exposure provokes long-lasting changes in the hippocampal subfields, induces motor impairments and increases the motivation-guided behavior. These findings can help understand the deleterious effect of CHX into the adult hippocampus and unveil its potential to trigger addiction-like behaviors.
Assuntos
Envelhecimento/patologia , Comportamento Animal , Cicloexanos/administração & dosagem , Hipocampo/patologia , Recompensa , Administração por Inalação , Animais , Região CA3 Hipocampal/metabolismo , Região CA3 Hipocampal/patologia , Contagem de Células , Giro Denteado/metabolismo , Giro Denteado/patologia , Hipocampo/metabolismo , Masculino , Camundongos , Motivação , Atividade Motora , Neuropeptídeo Y/metabolismo , Postura , Proteínas Proto-Oncogênicas c-fos/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Reforço Psicológico , Análise e Desempenho de TarefasRESUMO
El escrito ofrece un panorama general sobre el valor de la recompensa, respondiendo los interrogantes: ¿qué es?, ¿cómo se ha conceptualizado? y ¿qué investigaciones han utilizado el concepto? En sentido general, este se utiliza para calificar una recompensa como más o menos efectiva: mientras mayor sea el valor, mayor es su eficacia. Primero se describe la medición histórica del valor y cómo lo define la literatura sobre economía conductual. A continuación aparecen dos usos diferentes del concepto: (a) como constructo hipotético y (b) como variable interviniente. También se incluyen definiciones operacionales, en las que no se definen exhaustivamente las variables asociadas, entonces no se le considera variable interviniente, pero tampoco se agrega significado, más allá del nivel de observación, por lo que no son ejemplo de constructo hipotético. Posteriormente se explora la relación entre demora del reforzador y descuento temporal. Las consideraciones finales retoman la discusión sobre su valor heurístico en la investigación contemporánea.
The article offers a general panorama on the value of the reward, answering the questions: What is it? How has it been conceptualized? What investigations have used the concept? In general, a reward is rated as more or less effective: the greater the value, the greater its efficiency. First, the article discusses the historical measurement of value and how the literature on behavioral economics defines it. Next, two different uses of the concept are presented: (a) as a hypothetical construct and (b) as intervening variable. The text includes operational definitions where the associated variables are not defined exhaustively and therefore not considered as intervening variable, but which also add no meaning beyond the level of observation and therefore are not an example of a hypothetical construct. The article then explores the relationship between delay of the reinforcing agent and temporal discount. Finally, the article considers the discussion about the concept's heuristic value in contemporary research.
Este texto oferece um panorama geral sobre o valor da recompensa ao responder aos questionamentos: o que é, como vem sendo conceituado e quais pesquisas têm utilizado o conceito? Em sentido geral, este se utiliza para qualificar uma recompensa como mais ou menos efetiva: quanto maior for o valor, maior será sua eficácia. Primeiramente, descreve-se a medição histórica do valor e como a literatura sobre economia comportamental o define. A seguir, aparecem dois usos diferentes do conceito: (a) como construto hipotético e (b) como variável interventora. Também são incluídas definições operacionais, nas quais não se definem exaustivamente as variáveis associadas, portanto não é considerada variável interventora nem se agrega significado mais além do nível de observação, razão pela qual não são exemplos de construto hipotético. Posteriormente, explora-se a relação entre demora do reforçador e desconto temporal. As considerações finais retomam a discussão sobre seu valor heurístico na pesquisa contemporânea.
RESUMO
Japanese quail (Coturnix japonica) were reinforced with food for traversing a runway for either 18 or 36 trials, administered at a rate of 1 trial per day. Then, all animals received 18 extinction trials. The latency to run from the start box to the goal box was the dependent variable. Extinction was significantly slower in animals that had received 50% partial reinforcement during acquisition, whether relative to a group matched in terms of acquisition trials (36 trials, twice the number of reinforced trials) or relative to a group matched in terms of reinforcements (18 trials). The latter group was also matched in terms of the temporal distribution of acquisition trials with the partial reinforcement group, being trained only on days when the partial group was scheduled to receive a reinforced trial. Thus, there was evidence of a spaced-trial partial reinforcement extinction effect. A comparison of groups receiving large versus small reward magnitudes yielded no evidence of the spaced-trial magnitude of reinforcement extinction effect, even though the large-reward group consumed approximately 3 times more food than the small-reward group. Moreover, a comparison of groups that received 36 versus 18 acquisition trials produced no evidence of the spaced-trial overtraining extinction effect, even though acquisition latencies were significantly lower for the group that received 36 acquisition trials. These results are discussed in relation to comparative research on learning phenomena involving incentive downshift manipulations.