Assessment of metabolic changes in the striatum of a MPTP-intoxicated canine model: in vivo 1H-MRS study of an animal model for Parkinson's disease

Choi, Chi-Bong; Kim, Sang-Young; Lee, Sungho; Jahng, Geon‐Ho; Kim, Hwi-Yool; Choe, Bo-Young; Ryu, Kyung Nam; Yang, Dal-Mo; Yim, Sung-Vin; Choi, Woo Suk

doi:10.1016/j.mri.2010.03.043

Cited by 13 publications

(7 citation statements)

References 51 publications

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“…In C57B1/6J mice given MPTP injections, the extent of dopamine denervation in the substantia nigra and ventral tegmental area was related to increased concentrations of glutamate, glutamine, and GABA in the dorsal and ventral striatum, respectively (Chassain et al, 2013). Contrary to the previous findings in rodents, MPTP administration in adult beagles did not affect the concentration of glutamate + glutamine/creatine ratio in the striatum assessed at 3-T (Choi et al, 2011). However, it is important to note that all of the aforementioned in vivo 1 H-MRS studies were performed while the animals were under anesthesia, and it is unknown how this affects glutamate, glutamine, and GABA levels in combination with chemically induced dopamine denervation (Pfeuffer et al, 2004).…”

Section: In Vivo 1 H-mrs In Rodentscontrasting

confidence: 59%

The effect of striatal dopamine depletion on striatal and cortical glutamate: A mini-review

Caravaggio

Nakajima

Plitman

et al. 2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Understanding the interplay between the neurotransmitters dopamine and glutamate in the striatum has become the highlight of several theories of neuropsychiatric illnesses, such as schizophrenia. Using in vivo brain imaging in humans, alterations in dopamine and glutamate concentrations have been observed in several neuropsychiatric disorders. However, it is unclear a priori how alterations in striatal dopamine should modulate glutamate concentrations in the basal ganglia. In this selective mini-review, we examine the consequence of reducing striatal dopamine functioning on glutamate concentrations in the striatum and cortex; regions of interest heavily examined in the human brain imaging studies. We examine the predictions of the classical model of the basal ganglia, and contrast it with findings in humans and animals. The review concludes that chronic dopamine depletion (>4 months) produces decreases in striatal glutamate levels which are consistent with the classical model of the basal ganglia. However, acute alterations in striatal dopamine functioning, specifically at the D2 receptors, may produce opposite affects. This has important implications for models of the basal ganglia and theorizing about neurochemical alterations in neuropsychiatric diseases. Moreover, these findings may help guide a priori hypotheses for 1H-MRS studies measuring glutamate changes given alterations in dopaminergic functioning in humans.

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Section: In Vivo 1 H-mrs In Rodentscontrasting

confidence: 59%

The effect of striatal dopamine depletion on striatal and cortical glutamate: A mini-review

Caravaggio

Nakajima

Plitman

et al. 2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…In our study, the Glu levels as well as Glx (Glu + Gln) levels in the STR did not differ among the experimental groups, which is in line with previous findings in PD patients 23,25,29 and MPTP-intoxicated canine 14 or feline 20 models of PD. Unchanged Glu levels were also reported in the dopamine-denervated STR of 6-OHDA-treated rats.…”

Section: Striatal Glu and Gpc Levelssupporting

confidence: 92%

“…7,22,78,79 However, the nigral and striatal tCho levels did not differ among the experimental groups in our study. Several recent 1 H-MRS studies have also reported no changes in striatal tCho in PD patients, 23 MPTP-intoxicated mice and dogs, 12,14 or 6-OHDA-treated rats. 15 Therefore, the unchanged tCho levels in our study also require further investigation together with the striatal Glu levels.…”

Section: Striatal Glu and Gpc Levelsmentioning

confidence: 91%

“…1 The neurochemical information in PD brain is important for elucidating the pathogenesis and progression of the disease. 7,8 To this end, proton MRS ( 1 H-MRS) has been used in the PD research in animals 7,[9][10][11][12][13][14][15][16][17][18][19][20][21] and human patients. [22][23][24][25][26][27][28][29] For instance, using 1 H-MRS, reduction in N-acetylaspartate (NAA) levels and elevation in glutamate (Glu), γ-aminobutyric acid (GABA), choline (Cho) and lactate (Lac) levels were found in the striatum (STR) of rodent PD models.…”

Section: Introductionmentioning

confidence: 99%

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Neurometabolic profiles of the substantia nigra and striatum of MPTP‐intoxicated common marmosets: An in vivo proton MRS study at 9.4 T

et al. 2016

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Given the strong coupling between the substantia nigra (SN) and striatum (STR) in the early stage of Parkinson's disease (PD), yet only a few studies reported to date that have simultaneously investigated the neurochemistry of these two brain regions in vivo, we performed longitudinal metabolic profiling in the SN and STR of 1-methyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated common marmoset monkey models of PD (n = 10) by using proton MRS ( H-MRS) at 9.4 T. T relaxometry was also performed in the SN by using MRI. Data were classified into control, MPTP_2weeks, and MPTP_6-10 weeks groups according to the treatment duration. In the SN, T of the MPTP_6-10 weeks group was lower than that of the control group (44.33 ± 1.75 versus 47.21 ± 2.47 ms, p < 0.05). The N-acetylaspartate to total creatine ratio (NAA/tCr) and γ-aminobutyric acid to tCr ratio (GABA/tCr) of the MPTP_6-10 weeks group were lower than those of the control group (0.41 ± 0.04 versus 0.54 ± 0.08 (p < 0.01) and 0.19 ± 0.03 versus 0.30 ± 0.09 (p < 0.05), respectively). The glutathione to tCr ratio (GSH/tCr) was correlated with T for the MPTP_6-10 weeks group (r = 0.83, p = 0.04). In the STR, however, GABA/tCr of the MPTP_6-10 weeks group was higher than that of the control group (0.25 ± 0.10 versus 0.16 ± 0.05, p < 0.05). These findings may be an in vivo depiction of the altered basal ganglion circuit in PD brain resulting from the degeneration of nigral dopaminergic neurons and disruption of nigrostriatal dopaminergic projections. Given the important role of non-human primates in translational studies, our findings provide better understanding of the complicated evolution of PD.

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“…Reduced NAA and increased lactate levels were observed in the striatum or substantia nigra of mouse (Boska et al, 2005;Koga et al, 2006), rat (Jenkins et al, 1996;Storey et al, 1992), feline (Podell et al, 2003), canine (Choi et al, 2011) or primate (Brownell et al, 1998) MPTP/ MPP + -intoxicated models, suggesting neuronal loss and mitochondrial dysfunction. GABA was suggested to be either increased (Chassain et al, 2008(Chassain et al, , 2010 of reduced (Storey et al, 1992) after MPTP/MPP + treatment.…”

Section: Parkinson's Diseasementioning

confidence: 98%

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

et al. 2012

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Assessment of metabolic changes in the striatum of a MPTP-intoxicated canine model: in vivo 1H-MRS study of an animal model for Parkinson's disease

Cited by 13 publications

References 51 publications

The effect of striatal dopamine depletion on striatal and cortical glutamate: A mini-review

The effect of striatal dopamine depletion on striatal and cortical glutamate: A mini-review

Neurometabolic profiles of the substantia nigra and striatum of MPTP‐intoxicated common marmosets: An in vivo proton MRS study at 9.4 T

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

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