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Published on: January 7, 2014
Acute MPTP Treatment Impairs Dendritic Spine Density in the Mouse Hippocampus
Poornima D E Weerasinghe-Mudiyanselage1, Mary Jasmin Ang1,2, Mai Wada1
1Department of Veterinary Anatomy, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Korea.
Abstract:
Among the animal models of Parkinson's disease (PD), the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model has shown both dopaminergic (DA) damage and related motor control defects, as observed in patients with PD. Recent studies have suggested that the DA system interacts with the synaptic plasticity of the hippocampus in PD. However, little is known about how alterations in the hippocampal structural plasticity are affected by the DA damage in MPTP-lesioned models. In the present study, we investigated alterations in dendritic complexity and spine density in the mouse hippocampus following acute MPTP treatment (22 mg/kg, intraperitoneally, four times/day, 2-h intervals). We confirmed that acute MPTP treatment significantly decreased initial motor function and persistently reduced the number of tyrosine hydroxylase-positive DA neurons in the substantia nigra. Golgi staining showed that acute MPTP treatment significantly reduced the spine density of neuronal dendrites in the cornu ammonis 1 (CA1) apical/basal and dentate gyrus (DG) subregions of the mouse hippocampus at 8 and 16 days after treatment, although it did not affect dendritic complexity (e.g., number of crossing dendrites, total dendritic length, and branch points per neuron) in both CA1 and DG subregions at all time points after treatment. Therefore, the present study provides anatomical evidence that acute MPTP treatment affects synaptic structure in the hippocampus during the late phase after acute MPTP treatment in mice, independent of any changes in the dendritic arborization of hippocampal neurons. These findings offer data for the ability of the acute MPTP-lesioned mouse model to replicate the non-nigrostriatal lesions of clinical PD.
Insights
Acute MPTP treatment in mice damages dopaminergic neurons and impairs motor function. It also reduces synaptic spine density in the hippocampus, but not dendritic complexity, offering insights into Parkinson's disease models.
Area of Science:
- Neuroscience
- Neurobiology
- Parkinson's Disease Research
Background:
- Parkinson's disease (PD) animal models, like the MPTP-lesioned mouse, exhibit dopaminergic (DA) deficits and motor impairments.
- The interaction between the DA system and hippocampal synaptic plasticity in PD is an emerging area of study.
- Understanding how DA damage affects hippocampal structural plasticity in PD models is crucial.
Purpose of the Study:
- To investigate alterations in hippocampal dendritic complexity and spine density following acute MPTP treatment in mice.
- To determine the impact of DA damage on the structural plasticity of hippocampal subregions (CA1 and DG).
Main Methods:
- Mice received acute MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) injections.
- Motor function and dopaminergic neuron counts (tyrosine hydroxylase-positive) were assessed.
- Golgi staining was used to analyze dendritic complexity and spine density in hippocampal CA1 and DG subregions at 8 and 16 days post-treatment.
Main Results:
- Acute MPTP treatment confirmed reduced motor function and persistent loss of DA neurons in the substantia nigra.
- Significant reduction in neuronal dendritic spine density was observed in CA1 and DG subregions 8 and 16 days after MPTP treatment.
- No significant changes in dendritic complexity (branching, length) were found in the CA1 and DG subregions at any time point.
Conclusions:
- Acute MPTP treatment induces synaptic structural changes in the mouse hippocampus, specifically reduced spine density, during the late phase post-treatment.
- These hippocampal alterations occur independently of changes in dendritic arborization.
- The findings support the utility of the acute MPTP-lesioned mouse model for studying non-nigrostriatal lesions relevant to clinical Parkinson's disease.
