Biochemical alterations of the striatum in an MPTP-treated mouse model of Parkinson’s disease

Abstract

We investigated the biochemical alterations of the striatum of mice subjected to seven experimental schedules with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) treatment. The mice were treated intraperitoneally (i.p.) with MPTP (20 mg/kg in saline) four times a day at 2-hr intervals showed severe and persistent depletions of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum, as compared with those (1) treated with MPTP (15 mg/kg in saline, i.p.) once a day for 14 consecutive days; (2)MPTP (30 mg/kg in saline, i.p.) twice a day for 5 consecutive days; (3) MPTP (10 mg/kg in saline, i.p.) four times a day at 1-hr intervals for 2 consecutive days; (4) MPTP (20 mg/kg in saline, i.p.) once a day for 4 consecutive days; (5) MPTP (20 mg/kg in saline, i.p.) twice a day for 2 consecutive days; (6) MPTP (20 mg/kg in saline, i.p.) twice a day for 4 consecutive days. In our Western blot analysis, furthermore, the mice that received MPTP (20 mg/kg in saline) four times a day at 2-hr intervals showed a severe decrease of the striatal tyrosine hydroxylase (TH) protein levels and a significant increase of the striatal glial fibrillary acidic protein (GFAP) levels. These results demonstrate that the model with acute MPTP treatment can cause severe neuronal damage in the mouse striatum, as compared to the model with continuous treatment with MPTP. Thus our findings may support the validity of acute MPTP treatment model for unraveling in the neurodegenerative processes in PD.

New 6-Aminoquinoxaline Derivatives with Neuroprotective Effect on Dopaminergic Neurons in Cellular and Animal Parkinson Disease Models

“…39,40 When C57BL/6 mice received a MPTP sub-chronic treatment, we observed a substantial loss of nigrostriatal DA neurons. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 This led to reduced levels of DA and its metabolites DOPAC and HVA in the striatum and to an increased DA turnover reflected by a rise in the DOPAC+HVA/DA ratio.…”

“…This PD model reproduces a number of pathological processes, such as oxidative stress, mitochondrial dysfunction, andinflammation that are thought to participate in disease progression 38,39. Herein, C57BL/6 mice received a sub-chronic MPTP treatment in order to induce the degeneration of nigrostriatal DA neurons and a depletion in striatal DA and related metabolites 40. …”

Neuroprotective Effects of β-Caryophyllene against Dopaminergic Neuron Injury in a Murine Model of Parkinson’s Disease Induced by MPTP

“…; Sigma-Aldrich, St. Louis, MO, USA) being administered daily for five consecutive days. The MPTP administration conditions and dosage were selected based on previous studies [ 61 ] in which dopamine depletion, apoptosis, inflammatory response, and oxidative damage were demonstrated in mice subjected to MPTP under the same experimental conditions. The third group of mice was treated with BCP (10 mg/kg, i.p.)…”

Identification of a Novel 1,4,8-Triazaphenanthrene Derivative as a Neuroprotectant for Dopamine Neurons Vulnerable in Parkinson’s Disease

“…More specifically, C57BL/6 mice were given MPTP in a sub-chronic manner so as to generate a progressive loss of SN DA neurons and cause concurrent deficits in DA and its metabolites in the striatum. 21,22,23 This experimental paradigm is of interest as it is thought to replicate some of the key events that contribute to PD progression. 21,22 SN DA neurons were identified by immunohistochemistry of the TH enzyme, using 3,3-diaminobenzidine (DAB) as a chromogen.…”