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Genetic effects in a progressive model of parkinsonism induced by reserpine

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Abstract

Objective and methods

We investigated the locomotor, emotional, physiological, and neurobiological effects induced by low-dose reserpine repeated treatment (0.1 mg/kg; 14 injections) in males from the Lewis (LEW), Spontaneously Hypertensive Rats (SHR), and SHR.LEW-(D4Rat76-D4Mgh11) (SLA16) isogenic rat strains, which have different genetic backgrounds on chromosome 4. Behavioral responses in the catalepsy, open-field, and oral movements’ tests were coupled with blood pressure, body weight, and striatal tyrosine hydroxylase (TH) level assessments to establish neurobiological comparisons between reserpine-induced impairments and genetic backgrounds

Results

Results revealed the SHR strain was more sensitive in the catalepsy test and exhibited higher TH immunoreactivity in the dorsal striatum. The SLA16 strain presented more oral movements, suggesting increased susceptibility to develop oral dyskinesia.

Conclusions

Our results showed the efficacy of repeated treatment with a low dose of reserpine and demonstrated, for the first time, the genetic influence of a specific region of chromosome 4 on the expression of these effects.

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Acknowledgements

The authors would like to thank the “Laboratório Multiusuário de Estudos em Biologia” at the Federal University of Santa Catarina (LAMEB/UFSC) for technical support in processing samples for the immunohistochemistry assay.

Funding

This work was supported by Conselho Nacional de Pesquisa e Desenvolvimento Tecnológico (CNPq) Grant No. 303325/2017–8, Edital MCT/CNPq 14/2010 and MCTI/CNPq 14/2013; and Fundação de Amparo à Pesquisa do Estado de São Paulo (Fapesp) Grant No. 2015/12308–5. G. P. Fadanni, N. Granzotto, and P.A.R dos Anjos were recipients of fellowships from CNPq. A.G. Pereira is supported by a scholarship from PNPD/CAPES.

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Authors and Affiliations

  1. Graduate Program of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil

    Guilherme Pasetto Fadanni, Natalli Granzotto, Pâmela Andressa Ramborger Anjos, Áurea Elizabeth Linder & Geison Souza Izídio

  2. Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil

    Anderson Henrique França Figueiredo Leão & Regina Helena Silva

  3. Graduate Program of Developmental and Cellular Biology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil

    Aline Guimarães Pereira & Geison Souza Izídio

  4. Laboratory of Behavioral and Evolutionary Neurobiology, Department of Biosciences, Universidade Federal de Sergipe, Itabaiana, Brazil

    Auderlan Mendonça de Gois & José Ronaldo Santos

  5. Biological Sciences Center, Cellular Biology, Embryology and Genetics Department, Behavioral Genetics Laboratory, Federal University of Santa Catarina, 88.040-900, Florianópolis, SC, Brazil

    Geison Souza Izídio

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  1. Guilherme Pasetto Fadanni
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Contributions

Guilherme Pasetto Fadanni participated in the research by doing experiments, analyzing data, and assisting in the writing of the manuscript. Anderson Henrique Leão participated in the research by doing experiments, analyzing data, and assisting in the writing of the manuscript. Natalli Granzotto participated in the research by doing experiments, analyzing data, and assisting in the writing of the manuscript. Aline Guimarães Pereira participated in the research by analyzing data and assisting in the writing of the manuscript. Auderlan Mendonça de Gois participated in the research by doing experiments, analyzing data, and assisting in the writing of the manuscript. Pâmela Andressa Ramborger Anjos participated in the research by doing experiments. Áurea Elizabeth Linder participated in the research by analyzing data and assisting in the writing of the manuscript. José Ronaldo Santos participated in the research by analyzing the data and assisting in the writing of the manuscript. Regina Helena Silva participated in the research by analyzing the data and assisting in the writing of the manuscript. Geison Souza Izídio participated in the research by analyzing the data and assisting in the writing of the manuscript.

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Correspondence to Geison Souza Izídio.

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All procedures were performed following the guidelines for animal care from “Conselho Nacional de Controle de Experimentação Animal” (CONCEA, Brazil) and following the specifications of the local ethics committee (CEUA/UFSC, Protocol No. PP00903). The experimental protocol was designed to minimize the number of animals and procedures involving stress, pain, or discomfort.

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Supplementary Information

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Supplementary Figure 1

Systolic blood pressure. Systolic blood pressure in Lewis (LEW), Spontaneously Hypertensive Rats (SHR) and SHR.LEW-(D4Rat76-D4Mgh11) isogenic rat strains (n = 8/strain/treatment) during repeated treatment with reserpine (RES, 0.1 mg/kg; 14 injections) or vehicle (VEH). Results are expressed as mean + S.E.M. ## = VEH>RES, p≤0.01; ** = SHR>LEW, p≤0.01 and SHR>SLA16, p≤0.05. Two-way ANOVA with repeated measures followed by Duncan's post hoc test (PNG 96 kb)

High resolution image (TIF 209 kb)

Supplementary Figure 2

Representation of chromosome 4 from SLA16 rats with positions of the molecular markers. The Differential Genomic Region (DGR) is represented in blue. The genetic background of SHR rats is represented in red. Some genes are mapped in the DGR region, for example, the Snca (alpha-synuclein), Grid2 (Glutamate Ionotropic Receptor Delta Type Subunit 2), Il12rb2 (Interleukin-12 receptor subunit beta-2), Tac1r (Tachykinin receptor 1), Grip2 (Glutamate Receptor Interacting Protein 2), Il5ra (Interleukin 5 receptor subunit alpha), Grm7 (Glutamate metabotropic receptor 7), Pparg (Peroxisome proliferator-activated receptor gamma), Grin2b (Glutamate ionotropic receptor NMDA type subunit 2B). (PNG 237 kb)

High resolution image (TIF 389 kb)

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Fadanni, G.P., Leão, A.H.F.F., Granzotto, N. et al. Genetic effects in a progressive model of parkinsonism induced by reserpine. Psychopharmacology 240, 1131–1142 (2023). https://doi.org/10.1007/s00213-023-06350-6

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