Spontaneously Hypertensive Rats (SHR) Are Resistant to a Reserpine-Induced Progressive Model of Parkinson's Disease: Differences in Motor Behavior, Tyrosine Hydroxylase and alpha-Synuclein Expression

Reserpine is an irreversible inhibitor of vesicular monoamine transporter-2 (VMAT2) used to study Parkinson's disease (PD) and screening for antiparkinsonian treatments in rodents. Recently, the repeated treatment with a low-dose of reserpine was proposed as a progressive model of PD. Rats under this treatment show progressive catalepsy behavior, oral movements and spontaneous motor activity decrement. In parallel, compared to Wistar rats, spontaneously hypertensive rats (SHR) are resistant to acute reserpine-induced oral dyskinesia. We aimed to assess whether SHR would present differential susceptibility to repeated reserpine-induced deficits in the progressive model of PD. Male Wistar and SHR rats were administered 15 subcutaneously (s.c.) injections of reserpine (0.1 mgkg) or vehicle, every other day and motor activity was assessed by the catalepsy, oral movements and open field tests. Only reserpine-treated Wistar rats presented increased latency to step down in the catalepsy test and impaired spontaneous activity in the open field. On the other hand, there was an increase in oral movements in both reserpine-treated strains, although with reduced magnitude and latency to instauration in SHR. After a 15-day withdrawn period, both strains recovered from motor impairment, but SHR animals expressed reduced latencies to reach control levels. Finally, we performed immunohistochemistry for tyrosine hydroxylase (TH) and a-synuclein (alpha-syn) 48 h after the last injection or 15 days after withdrawn. Reserpinetreated animals presented a reduction in TH and an increase in alpha-syn immunoreactivity in the substantia nigra and dorsal striatum (dSTR), which were both recovered after 15 days of withdraw. Furthermore, SHR rats were resistant to reserpine-induced TH decrement in the substantia nigra, and presented reduced immunoreactivity to a-syn inthe dSTR relative to Wistar rats, irrespective of treatment. This effect was accompanied by increase of malondaldhyde (MDA) in the striatum of reserpine-treated Wistar rats, while SHR presented reduced MDA in both control and reserpine conditions relative to Wistar strain. In conclusion, the current results show that SHR are resilient to motor and neurochemical impairments induced by the repeated low-dose reserpine protocol. These findings indicate that the neurochemical, molecular and genetic differences in the SHR strain are potential relevant targets to the study of susceptibility to PD.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Fundacao de Apoio a Pesquisa do Estado do Rio Grande do Norte (FAPERN)Pro-reitoria de Pesquisa da Universidade Federal do Rio Grande do Norte (PROPESQ/UFRN)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Univ Fed Rio Grande do Norte, Dept Physiol, Memory Studies Lab, Natal, RN, BrazilUniv Fed Rio Grande do Norte, Brain Inst, Natal, RN, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Behav Neurosci Lab, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, BrazilUniv Fed Rio Grande do Norte, Dept Physiol, Neurochem Studies Lab, Natal, RN, BrazilUniv Santa Catarina, Dept Cellular Biol Embryol & Genet, Lab Behav Genet, Florianopolis, SC, BrazilUniv Fed Sao Paulo, Dept Biosci, Santos, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Behav Neurosci Lab, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Biosci, Santos, BrazilFAPESP: 2015/12308-5FAPESP: 2015/03354-3Web of Scienc

Assessing the Effects of Personal Characteristics and Context on U.S. House Speakers’ Leadership Styles, 1789-2006

Research on congressional leadership has been dominated in recent decades by contextual interpretations that see leaders’ behavior as best explained by the environment in which they seek to exercise leadership—particularly, the preference homogeneity and size of their party caucus. The role of agency is thus discounted, and leaders’ personal characteristics and leadership styles are underplayed. Focusing specifically on the speakers of the U.S. House of Representatives from the first to the 110th Congress, we construct measures of each speaker’s commitment to comity and leadership assertiveness. We find the scores reliable and then test the extent to which a speaker’s style is the product of both political context and personal characteristics. Regression estimates on speakers’ personal assertiveness scores provide robust support for a context-plus-personal characteristics explanation, whereas estimates of their comity scores show that speakers’ personal backgrounds trump context

A reciprocal legitimation: Corrado Gini and statistics in fascist Italy

This article deals with the relationship between science and politics and in particular with the reciprocal legitimation process involving research schools and political regimes. It focuses on the case of Italian statistics during the early twentieth century. Its emergence as both an independent scientific field and a national research school, in fact, went together with the rise of nationalism and the establishment of the fascist regime. The paper uses the biography of Corrado Gini to analyze the process of mutual legitimization between science and politics under fascism. Gini's academic and professional careers show in fact how actors and ideas could compete through their ability to alter the status of the discipline, the technical functions it was assigned, and to attract funds in a changing political context Gini, as an institutional entrepreneur, was able to make his research school hegemonic in Italy by leveraging the need for scientific legitimation of new state policies during World War I and under fascism. The reinterpretation he provided of his career after the end of World War II is crucial both to deconstructing this process and to shedding light on the postwar de-legitimation of Italian statistics

Organisms in experimental research

Rachel A. Ankeny and Sabina Leonell

Cognitive, motor and tyrosine hydroxylase temporal impairment in a model of parkinsonism induced by reserpine

Studies have suggested that cognitive deficits can precede motor alterations in Parkinson's disease (PD). However, in general, classic animal models are based on severe motor impairment after one single administration of neurotoxins, and thereby do not express the progressive nature of the pathology. A previous study showed that the repeated administration with a low dose (0.1 mg/kg) of the monoamine depleting agent reserpine induces a gradual appearance of motor signs of pharmacological parkinsonism in rats. Here, we showed this repeated treatment with reserpine induced a memory impairment (evaluated by the novel object recognition task) before the gradual appearance of the motor signs. Additionally, these alterations were accompanied by decreased tyrosine hydroxylase (TH) striatal levels and reduced number of TH+ cells in substantia nigra pars compacta (SNpc). After 30 days without treatment, reserpine-treated animals showed normal levels of striatal TH, partial recovery of TH+ cells in SNpc, recovery of motor function, but not reversal of the memory impairment. Furthermore, the motor alterations were statistically correlated with decreased TH levels (GD, CA1, PFC and DS) and number of TH+ cells (SNpc and VTA) in the brain. Thus, we extended previous results showing that the gradual appearance of motor impairment induced by repeated treatment with a low dose of reserpine is preceded by short-term memory impairment, as well as accompanied by neurochemical alterations compatible with the pathology of PD. (C) 2013 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundacao de Apoio Pesquisa do Estado do Rio Grande do Norte (FAPERN)Pro-reitoria de Pesquisa da Universidade Federal do Rio Grande do Norte (PROPESQ/UFRN)Univ Fed Rio Grande do Norte, Dept Physiol, Lab Memory Studies, BR-59072970 Natal, RN, BrazilUniv Fed Rio Grande do Norte, Dept Morphol, Lab Neuroanat, BR-59072970 Natal, RN, BrazilUniv Fed Santa Catarina, Dept Cellular Biol Embryol & Genet, Florianopolis, SC, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, LiNC, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, LiNC, São Paulo, BrazilWeb of Scienc