Acute MPTP Treatment Impairs Dendritic Spine Density in the Mouse Hippocampus

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.

Acute MPTP treatment decreases dendritic spine density of striatal medium spiny neurons via SNK‐SPAR pathway in C57BL/6 mice

“…Collectively, our findings correspond to previous studies and anticipation (Villalba et al., 2009; Weerasinghe‐Mudiyanselage et al., 2021). The PD model has been successfully established in mice (Jenner, 2003); hence, determining the dendritic spine density of striatal MSNs and expression of SNK and SPAR can afford valuable insights.…”

Changes in the Neuronal Architecture of the Hippocampus in a 6-Hydroxydopamine-Lesioned Rat Model of Parkinson Disease

“…Structural plasticity in the hippocampus can be influenced by a variety of stimuli, some of which appear to have long-term effects [ 8 ]. Previous studies found that dendritic complexity and/or spine density was altered in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned [ 17 , 18 ] and leucine-rich repeat kinase 2-mutant mouse PD models [ 19 , 20 ]. However, many questions remain unanswered about the functional and structural changes of hippocampal neurons that occur in PD.…”

Structural Plasticity of the Hippocampus in Neurodegenerative Diseases

“…Spine density in the hippocampal DG region was decreased in MPTP-lesioned mice along with a remarkable decrease in the proteins that mediated neuroplasticity mechanisms and impaired cognitive function [ 139 ]. Similarly, a recent study found decreased spine density in both CA1 and DG subregions of the MPTP-lesioned mice during the late phase of PD [ 289 ]. In LRRK2-mutant mice, newly generated DG neurons were found with reduced dendritic spines [ 288 ].…”

“…Dendritic length and branching were reduced in primary cultured hippocampal neurons [ 286 ] and newly generated DG neurons [ 287 , 288 ] in the LRRK2-mutant mice. However, a previous study showed that the dendritic complexity of both CA1 and DG subregions was not altered in the MPTP-lesioned mice [ 289 ]. Therefore, further studies are needed to confirm dendritic pathology in PD animal models, since variations in observations due to different models cannot be neglected.…”