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

Abstract

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 mg/kg) 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 After a 15-day withdrawn period, both strains recovered from motor impairment, but SHR animals expressed reduced latencies to reach control levels.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for tyrosine hydroxylase (TH) and α-synuclein (α-syn) 48 h after the last injection or 15 days after withdrawn. Reserpine-treated animals presented a reduction in TH and an increase in α-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 α-syn in the 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.

Authors+Show Affiliations

Memory Studies Laboratory, Department of Physiology, Federal University of Rio Grande do NorteNatal, Brazil; Brain Institute, Federal University of Rio Grande do NorteNatal, Brazil; Behavioral Neuroscience Laboratory, Department of Pharmacology, Federal University of São PauloSão Paulo, Brazil.Memory Studies Laboratory, Department of Physiology, Federal University of Rio Grande do Norte Natal, Brazil.Brain Institute, Federal University of Rio Grande do Norte Natal, Brazil.Behavioral Neuroscience Laboratory, Department of Pharmacology, Federal University of São Paulo São Paulo, Brazil.Memory Studies Laboratory, Department of Physiology, Federal University of Rio Grande do Norte Natal, Brazil.Department of Pharmacology, Federal University of São Paulo São Paulo, Brazil.Neurochemical Studies Laboratory, Department of Physiology, Federal University of Rio Grande do Norte Natal, Brazil.Neurochemical Studies Laboratory, Department of Physiology, Federal University of Rio Grande do Norte Natal, Brazil.Laboratory of Behavioral Genetics, Department of Cellular Biology, Embryology and Genetics, Federal University of Santa Catarina Florianopolis, Brazil.Department of Biosciences, Federal University of São Paulo Santos, Brazil.Memory Studies Laboratory, Department of Physiology, Federal University of Rio Grande do NorteNatal, Brazil; Behavioral Neuroscience Laboratory, Department of Pharmacology, Federal University of São PauloSão Paulo, Brazil.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28396635

Citation

Leão, Anderson H F F., et al. "Spontaneously Hypertensive Rats (SHR) Are Resistant to a Reserpine-Induced Progressive Model of Parkinson's Disease: Differences in Motor Behavior, Tyrosine Hydroxylase and α-Synuclein Expression." Frontiers in Aging Neuroscience, vol. 9, 2017, p. 78.
Leão AH, Meurer YS, da Silva AF, et al. Spontaneously Hypertensive Rats (SHR) Are Resistant to a Reserpine-Induced Progressive Model of Parkinson's Disease: Differences in Motor Behavior, Tyrosine Hydroxylase and α-Synuclein Expression. Front Aging Neurosci. 2017;9:78.
Leão, A. H., Meurer, Y. S., da Silva, A. F., Medeiros, A. M., Campêlo, C. L., Abílio, V. C., ... Silva, R. H. (2017). Spontaneously Hypertensive Rats (SHR) Are Resistant to a Reserpine-Induced Progressive Model of Parkinson's Disease: Differences in Motor Behavior, Tyrosine Hydroxylase and α-Synuclein Expression. Frontiers in Aging Neuroscience, 9, p. 78. doi:10.3389/fnagi.2017.00078.
Leão AH, et al. Spontaneously Hypertensive Rats (SHR) Are Resistant to a Reserpine-Induced Progressive Model of Parkinson's Disease: Differences in Motor Behavior, Tyrosine Hydroxylase and α-Synuclein Expression. Front Aging Neurosci. 2017;9:78. PubMed PMID: 28396635.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spontaneously Hypertensive Rats (SHR) Are Resistant to a Reserpine-Induced Progressive Model of Parkinson's Disease: Differences in Motor Behavior, Tyrosine Hydroxylase and α-Synuclein Expression. AU - Leão,Anderson H F F, AU - Meurer,Ywlliane S R, AU - da Silva,Anatildes F, AU - Medeiros,André M, AU - Campêlo,Clarissa L C, AU - Abílio,Vanessa C, AU - Engelberth,Rovena C G K, AU - Cavalcante,Jeferson S, AU - Izídio,Geison S, AU - Ribeiro,Alessandra M, AU - Silva,Regina H, Y1 - 2017/03/27/ PY - 2016/07/28/received PY - 2017/03/13/accepted PY - 2017/4/12/entrez PY - 2017/4/12/pubmed PY - 2017/4/12/medline KW - Parkinson’s disease KW - SHR KW - reserpine KW - tyrosine hydroxylase KW - α-synuclein SP - 78 EP - 78 JF - Frontiers in aging neuroscience JO - Front Aging Neurosci VL - 9 N2 - 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 mg/kg) 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 α-synuclein (α-syn) 48 h after the last injection or 15 days after withdrawn. Reserpine-treated animals presented a reduction in TH and an increase in α-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 α-syn in the 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. SN - 1663-4365 UR - https://www.unboundmedicine.com/medline/citation/28396635/Spontaneously_Hypertensive_Rats__SHR__Are_Resistant_to_a_Reserpine_Induced_Progressive_Model_of_Parkinson's_Disease:_Differences_in_Motor_Behavior_Tyrosine_Hydroxylase_and_α_Synuclein_Expression_ L2 - https://doi.org/10.3389/fnagi.2017.00078 DB - PRIME DP - Unbound Medicine ER -