Investigation of tyrosine hydroxylase and BDNF in a low-dose rotenone model of Parkinson's disease

Michaela E. Johnson; Yoon Lim; Manjula Senthilkumaran; Xin Fu Zhou; Larisa Bobrovskaya

doi:10.1016/j.jchemneu.2015.11.002

Investigation of tyrosine hydroxylase and BDNF in a low-dose rotenone model of Parkinson's disease

Michaela E. Johnson, Yoon Lim, Manjula Senthilkumaran, Xin Fu Zhou, Larisa Bobrovskaya

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31 Citations (Scopus)

Abstract

Tyrosine hydroxylase (TH, the rate limiting-enzyme in catecholamine synthesis) is regulated acutely via phosphorylation of 3 serine residues-Ser19, 31 and 40, and chronically via changes in TH protein levels. In this study, we aimed to investigate how TH is regulated in the brain, gut and adrenal gland as well as changes in mature brain-derived neurotrophic factor (mBDNF) and proBDNF levels in a low-dose (2 mg/kg, 5 days/week for 4 weeks) rotenone model of Parkinson's disease (PD). Rearing behaviour decreased by week 3 in the rotenone group ( p< 0.01), with further decreases in rearing by week 4 ( p< 0.001); however, TH remained unchanged in the substantia nigra (SN) and striatum; TH levels were also unaltered in other catecholaminergic cell groups of the brainstem such as A1C1 neurons or locus coeruleus. In the olfactory bulb, TH protein decreased (2.5-fold, p< 0.01) while Ser31 phosphorylation increased (1.4-fold, p< 0.05) in the rotenone group. In contrast, TH protein was increased in the adrenal gland (2-fold, p< 0.05) and colon (5-fold, p< 0.05) of rotenone rats. mBDNF levels were not changed in the SN but were significantly reduced in plasma and significantly increased in the colon (2-fold, p< 0.01) of rotenone-treated rats. This is the first study to assess TH and BDNF in the brain and periphery in the rotenone model before SN/striatum degeneration is evident. Together these results suggest that low-dose rotenone may have some potential to model the early stages of PD.

Original language	English
Pages (from-to)	33-41
Number of pages	9
Journal	Journal of Chemical Neuroanatomy
Volume	70
DOIs	https://doi.org/10.1016/j.jchemneu.2015.11.002
Publication status	Published - Dec 2015
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by the University of South Australia. MEJ is a recipient of the Australian Postgraduate Award and MS is a recipient of the University of South Australia Postgraduate Award; both authors also receive the University of South Australia top up scholarship. YL was supported by a National health and Medical Research Council (NHMRC) Post-graduate Scholarship (GNT1017711). We would like to acknowledge the Reid animal facility staff for the help caring for the animals during the trial.

Publisher Copyright:
© 2015 Elsevier B.V.

Keywords

Brain-derived neurotrophic factor
Parkinson's disease
Rotenone
Tyrosine hydroxylase

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title = "Investigation of tyrosine hydroxylase and BDNF in a low-dose rotenone model of Parkinson's disease",

abstract = "Tyrosine hydroxylase (TH, the rate limiting-enzyme in catecholamine synthesis) is regulated acutely via phosphorylation of 3 serine residues-Ser19, 31 and 40, and chronically via changes in TH protein levels. In this study, we aimed to investigate how TH is regulated in the brain, gut and adrenal gland as well as changes in mature brain-derived neurotrophic factor (mBDNF) and proBDNF levels in a low-dose (2 mg/kg, 5 days/week for 4 weeks) rotenone model of Parkinson's disease (PD). Rearing behaviour decreased by week 3 in the rotenone group ( p< 0.01), with further decreases in rearing by week 4 ( p< 0.001); however, TH remained unchanged in the substantia nigra (SN) and striatum; TH levels were also unaltered in other catecholaminergic cell groups of the brainstem such as A1C1 neurons or locus coeruleus. In the olfactory bulb, TH protein decreased (2.5-fold, p< 0.01) while Ser31 phosphorylation increased (1.4-fold, p< 0.05) in the rotenone group. In contrast, TH protein was increased in the adrenal gland (2-fold, p< 0.05) and colon (5-fold, p< 0.05) of rotenone rats. mBDNF levels were not changed in the SN but were significantly reduced in plasma and significantly increased in the colon (2-fold, p< 0.01) of rotenone-treated rats. This is the first study to assess TH and BDNF in the brain and periphery in the rotenone model before SN/striatum degeneration is evident. Together these results suggest that low-dose rotenone may have some potential to model the early stages of PD.",

keywords = "Brain-derived neurotrophic factor, Parkinson's disease, Rotenone, Tyrosine hydroxylase",

author = "Johnson, {Michaela E.} and Yoon Lim and Manjula Senthilkumaran and Zhou, {Xin Fu} and Larisa Bobrovskaya",

note = "Funding Information: This work was supported by the University of South Australia. MEJ is a recipient of the Australian Postgraduate Award and MS is a recipient of the University of South Australia Postgraduate Award; both authors also receive the University of South Australia top up scholarship. YL was supported by a National health and Medical Research Council (NHMRC) Post-graduate Scholarship (GNT1017711). We would like to acknowledge the Reid animal facility staff for the help caring for the animals during the trial. Publisher Copyright: {\textcopyright} 2015 Elsevier B.V.",

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AU - Zhou, Xin Fu

AU - Bobrovskaya, Larisa

N1 - Funding Information: This work was supported by the University of South Australia. MEJ is a recipient of the Australian Postgraduate Award and MS is a recipient of the University of South Australia Postgraduate Award; both authors also receive the University of South Australia top up scholarship. YL was supported by a National health and Medical Research Council (NHMRC) Post-graduate Scholarship (GNT1017711). We would like to acknowledge the Reid animal facility staff for the help caring for the animals during the trial. Publisher Copyright: © 2015 Elsevier B.V.

PY - 2015/12

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N2 - Tyrosine hydroxylase (TH, the rate limiting-enzyme in catecholamine synthesis) is regulated acutely via phosphorylation of 3 serine residues-Ser19, 31 and 40, and chronically via changes in TH protein levels. In this study, we aimed to investigate how TH is regulated in the brain, gut and adrenal gland as well as changes in mature brain-derived neurotrophic factor (mBDNF) and proBDNF levels in a low-dose (2 mg/kg, 5 days/week for 4 weeks) rotenone model of Parkinson's disease (PD). Rearing behaviour decreased by week 3 in the rotenone group ( p< 0.01), with further decreases in rearing by week 4 ( p< 0.001); however, TH remained unchanged in the substantia nigra (SN) and striatum; TH levels were also unaltered in other catecholaminergic cell groups of the brainstem such as A1C1 neurons or locus coeruleus. In the olfactory bulb, TH protein decreased (2.5-fold, p< 0.01) while Ser31 phosphorylation increased (1.4-fold, p< 0.05) in the rotenone group. In contrast, TH protein was increased in the adrenal gland (2-fold, p< 0.05) and colon (5-fold, p< 0.05) of rotenone rats. mBDNF levels were not changed in the SN but were significantly reduced in plasma and significantly increased in the colon (2-fold, p< 0.01) of rotenone-treated rats. This is the first study to assess TH and BDNF in the brain and periphery in the rotenone model before SN/striatum degeneration is evident. Together these results suggest that low-dose rotenone may have some potential to model the early stages of PD.

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Investigation of tyrosine hydroxylase and BDNF in a low-dose rotenone model of Parkinson's disease

Abstract

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Keywords

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