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MPTP Neurotoxicity and Testosterone Induce Dendritic Remodeling of Striatal Medium Spiny Neurons in the C57Bl/6 Mouse
Eleni Antzoulatos1, Michael W Jakowec, Giselle M Petzinger
1Neuroscience Graduate Program, University of Southern California, Los Angeles, CA 90033, USA.
Abstract:
Nigrostriatal damage is increased in males relative to females. While estrogen is neuroprotective in females, less is known about potential protective effects of testosterone in males. We determined if castration enhances neuronal injury to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Castrates or sham-castrated mice were sacrificed 1 week following injection of MPTP (4 × 20 mg/kg) or saline (n = 11-12/group). The right striatum was immunostained for tyrosine hydroxylase (TH). The left hemisphere was stained by Golgi Cox to quantify neuronal morphology in medium spiny neurons (MSNs) of the dorsolateral striatum. MPTP reduced TH, but there was no effect of castration and no interaction. For MSN dendritic morphology, MPTP decreased the highest branch order and increased spine density on 2nd-order dendrites. Castrated males had shorter 5th-order dendrites. However, there was no interaction between gonadal status and MPTP. Thus, castration and MPTP exert nonoverlapping effects on MSN morphology with castration acting on distal dendrites and MPTP acting proximally.
Insights
Testosterone’s protective effects in males against neurodegeneration are unclear. Castration did not worsen 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced nigrostriatal damage or alter medium spiny neuron morphology.
Area of Science:
- Neuroscience
- Neurobiology
- Endocrinology
Background:
- Nigrostriatal pathway damage is more severe in males than females.
- Estrogen demonstrates neuroprotective properties in females, but testosterone's role in males is less understood.
- The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is used to model Parkinson's disease.
Purpose of the Study:
- To investigate whether castration exacerbates MPTP-induced neuronal injury in male mice.
- To examine the effects of castration and MPTP on medium spiny neuron (MSN) morphology in the dorsolateral striatum.
Main Methods:
- Male mice underwent either castration or sham castration.
- Mice were injected with MPTP or saline.
- Tyrosine hydroxylase (TH) levels were assessed in the striatum.
- Golgi Cox staining was used to analyze MSN dendritic morphology.
Main Results:
- MPTP reduced TH levels, but castration had no significant effect, and there was no interaction between castration and MPTP.
- MPTP altered MSN dendritic morphology by decreasing the highest branch order and increasing spine density on second-order dendrites.
- Castration resulted in shorter fifth-order dendrites, but no interaction with MPTP was observed.
Conclusions:
- Castration and MPTP induce separate, non-overlapping changes in MSN morphology.
- Castration affects distal dendritic processes, while MPTP impacts proximal ones.
- This study suggests testosterone does not play a significant role in protecting against MPTP-induced nigrostriatal damage or altering MSN morphology in this model.
