Single low doses of MPTP decrease tyrosine hydroxylase expression in the absence of overt neuron loss.

Title

Single low doses of MPTP decrease tyrosine hydroxylase expression in the absence of overt neuron loss.

Creator

Alam Gelareh; Edler Melissa; Burchfield Shelbie L; Richardson Jason R

Publisher

Neurotoxicology

Date

2017
2017-05

Description

Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a prototypical neurotoxicant used in mice to mimic primary features of PD pathology including striatal dopamine depletion and dopamine neuron loss in the substantia nigra pars compacta (SNc). In the literature, there are several experimental paradigms involving multiple doses of MPTP that are used to elicit dopamine neuron loss. However, a recent study reported that a single low dose caused significant loss of dopamine neurons. Here, we determined the effect of a single intraperitoneal injection of one of three doses of MPTP (0.1, 2 and 20mg/kg) on dopamine neurons, labeled by tyrosine hydroxylase (TH(+)), and total neuron number (Nissl(+)) in the SNc using unbiased stereological counting. Data reveal a significant loss of neurons in the SNc (TH(+) and Nissl(+)) only in the group treated with 20mg/kg MPTP. Groups treated with lower dose of MPTP (0.1 and 2mg/kg) only showed significant loss of TH(+) neurons rather than TH(+) and Nissl(+) neurons. Striatal dopamine levels were decreased in the groups treated with 2 and 20mg/kg MPTP and striatal terminal markers including, TH and the dopamine transporter (DAT), were only decreased in the groups treated with 20mg/kg MPTP. These data demonstrate that lower doses of MPTP likely result in loss of TH expression rather than actual dopamine neuron loss in the SN. This finding reinforces the need to measure both total neuron number along with TH(+) cells in determining dopamine neuron loss.

Subject

1-Methyl-4-phenyl-1; 2; 3; 6-tetrahydropyridine/*administration & dosage; Animals; Catecholamines/metabolism; Cell Count; Corpus Striatum/*drug effects/metabolism; Dopamine; Dopamine transporter; Dopaminergic Neurons/*drug effects/metabolism; Inbred C57BL; Male; Mice; MPTP; MPTP Poisoning; Parkinsonian Disorders/*metabolism/*pathology; Stereology; Substantia Nigra/*drug effects/metabolism; Tyrosine 3-Monooxygenase/*metabolism; Tyrosine hydroxylase; Vesicular monoamine transporter

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

99–106

Volume

60

Citation

Alam Gelareh; Edler Melissa; Burchfield Shelbie L; Richardson Jason R, “Single low doses of MPTP decrease tyrosine hydroxylase expression in the absence of overt neuron loss.,” NEOMED Bibliography Database, accessed April 12, 2021, https://neomed.omeka.net/items/show/3720.

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