期刊
BEHAVIOURAL BRAIN RESEARCH
卷 301, 期 -, 页码 43-54出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2015.12.011
关键词
Parkinson's disease; 6-OHDA; Non-motor symptoms; Short-term memory; Dorsolateral striatum; Medial prefrontal cortex
资金
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES-FCT)
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Fundacao de Apoio a Pesquisa do Estado de Santa Catarina (FAPESC)
- Programa de Apoio aos Nucleos de Excelencia (PRONEX - Project NENASC)
- DARPA [09-68-ESR-FP-010]
- Ciencia sem Fronteiras
- NARSAD
- QREN [09-68-ESR-FP-010]
- Santa Casa da Misericordia
- CNPq
Parkinson's disease (PD) is characterized by motor dysfunction associated with dopaminergic degeneration in the dorsolateral striatum (DLS). However, motor symptoms in PD are often preceded by short-term memory deficits, which have been argued to involve deregulation of medial prefrontal cortex (mPFC). We now used a 6-hydroxydopamine (6-OHDA) rat PD model to explore if alterations of synaptic plasticity in DLS and mPFC underlie short-term memory impairments in PD prodrome. The bilateral injection of 6-OHDA (20 mu g/hemisphere) in the DLS caused a marked loss of dopaminergic neurons in the substantia nigra (>80%) and decreased monoamine levels in the striatum and PFC, accompanied by motor deficits evaluated after 21 days in the open field and accelerated rotarod. A lower dose of 6-OHDA (10 mu g/hemisphere) only induced a partial degeneration (about 60%) of dopaminergic neurons in the substantia nigra with no gross motor impairments, thus mimicking an early premotor stage of PD. Notably, 6-OHDA (10 mu g)-lesioned rats displayed decreased monoamine levels in the PFC as well as short-term memory deficits evaluated in the novel object discrimination and in the modified Y-maze tasks; this was accompanied by a selective decrease in the amplitude of long-term potentiation in the mPFC, but not in DLS, without changes of synaptic transmission in either brain regions. These results indicate that the short-term memory dysfunction predating the motor alterations in the 6-OHDA model of PD is associated with selective changes of information processing in PFC circuits, typified by persistent changes of synaptic plasticity. (C) 2015 Elsevier B.V. All rights reserved.
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