Changes in the mesocorticolimbic pathway after low dose reserpine-treatment in Wistar and Spontaneously Hypertensive Rats (SHR): Implications for cognitive deficits in a progressive animal model for Parkinson's disease
| Autor: | Anderson H.F.F. Leão, Thalma A. Freitas, I M Conceição, André de Macêdo Medeiros, Regina H. Silva, Geison S. Izídio, Vanessa C. Abílio, Alessandra Mussi Ribeiro, Ywlliane da Silva Rodrigues Meurer |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Parkinson's disease Reserpine Tyrosine 3-Monooxygenase Dopamine Hippocampus Prefrontal Cortex 03 medical and health sciences Behavioral Neuroscience 0302 clinical medicine Neurochemical Internal medicine Rats Inbred SHR medicine Animals Parkinson Disease Secondary Rats Wistar Prefrontal cortex 030304 developmental biology 0303 health sciences Tyrosine hydroxylase business.industry Dopaminergic Recognition Psychology medicine.disease Rats Disease Models Animal Endocrinology Vesicular Monoamine Transport Proteins business Cognition Disorders 030217 neurology & neurosurgery medicine.drug Signal Transduction |
| Zdroj: | Behavioural brain research. 410 |
| ISSN: | 1872-7549 |
| Popis: | Reserpine (RES) is an irreversible inhibitor of 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 model capable of emulating progressive neurochemical, motor and non-motor impairments in PD. Conversely, compared to Wistar rats, Spontaneously Hypertensive Rats (SHR) are resistant to motor changes induced by repeated treatment with a low dose of RES. However, such resistance has not yet been investigated for RES-induced non-motor impairments. We aimed to assess whether SHR would have differential susceptibility to the object recognition deficit induced by repeated low-dose reserpine treatment. We submitted male Wistar and SHR rats to repeated RES treatment (15 s.c. injections of 0.1 mg/kg, every other day) and assessed object memory acquisition and retrieval 48 h after the 6 th RES injection (immediately before the appearance of motor impairments). Only RES Wistar rats displayed memory impairment after reserpine treatment. On the other hand, untreated SHR rats displayed object recognition memory deficit, but RES treatment restored such deficits. We also performed immunohistochemistry for tyrosine hydroxylase (TH) and α-synuclein (α-syn) 48 h after the last RES injection. In a different set of animals submitted to the same treatment, we quantified DA, 5-HT and products of lipid peroxidation in the prefrontal cortex (PFC) and hippocampus (HPC). SHR presented increased constitutive levels of DA in the PFC and reduced immunoreactivity to TH in the medial PFC and dorsal HPC. Corroborating the behavioral findings, RES treatment restored those constitutive alterations in SHR. These findings indicate that the neurochemical, molecular and genetic differences in the SHR strain are potentially relevant targets to the study of susceptibility to diseases related to dopaminergic alterations. |
| Databáze: | OpenAIRE |
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