Age- and Duration-dependent Effects of MPTP on Cortical Serotonin Systems

Overview

Journal Neurosci Lett

Specialty Neurology

Date 2011 Oct 4

PMID 21964387

Citations 4

Authors

Twum A Ansah

Marcus C Ferguson

Tultul Nayyar

Ariel Y Deutch

Affiliations

Soon will be listed here.

Abstract

It has been well established that aging is the most prominent risk factor for PD. In the MPTP mouse model which has been widely used to study PD, studies have shown that MPTP exhibits its neurotoxic effects on the dopaminergic system in an age-dependent manner. Although it is recognized the serotonergic system is impacted in PD, how aging influences serotonergic neurodegeneration in PD has not been adequately investigated. In the present studies, we examined the long-term effects of MPTP treatment on regional concentrations of dopamine (DA), serotonin (5-HT) and norepinephrine (NE) in the striatum and prefrontal cortex (PFC). We also determined if there are differences in the age-dependent vulnerability of the monoaminergic system to MPTP. In young (3-month-old) mice, MPTP produced significant decreases in striatal DA but no changes in striatal 5-HT and NE three weeks after MPTP treatment. There was partial recovery of striatal DA concentrations 18 months later. This was accompanied by elevated striatal 5-HT. In the PFC, NE was decreased but there was complete recovery 18 months later. By contrast, we observed a long-term decrease in prefrontal 5-HT with no recovery of 5-HT concentrations 18 months after MPTP treatment. Striatal DA and NE but not 5-HT neurons exhibited age-dependent vulnerability to MPTP. Aging had no influence on the neurotoxic effects of MPTP in the PFC. Thus, there is divergence in the response of DA and 5-HT systems to MPTP neurotoxicity.

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References

Raz N, Head D, Dupuis J, Acker J . Neuroanatomical correlates of cognitive aging: evidence from structural magnetic resonance imaging. Neuropsychology. 1998; 12(1):95-114. DOI: 10.1037//0894-4105.12.1.95. View

Stephenson D, Ramirez A, Long J, Barrezueta N, Hajos-Korcsok E, Matherne C . Quantification of MPTP-induced dopaminergic neurodegeneration in the mouse substantia nigra by laser capture microdissection. J Neurosci Methods. 2006; 159(2):291-9. DOI: 10.1016/j.jneumeth.2006.07.027. View

Kostrzewa R, Reader T, Descarries L . Serotonin neural adaptations to ontogenetic loss of dopamine neurons in rat brain. J Neurochem. 1998; 70(3):889-98. DOI: 10.1046/j.1471-4159.1998.70030889.x. View

Zhou F, Liang Y, Salas R, Zhang L, De Biasi M, Dani J . Corelease of dopamine and serotonin from striatal dopamine terminals. Neuron. 2005; 46(1):65-74. DOI: 10.1016/j.neuron.2005.02.010. View

Agid Y . Parkinson's disease: pathophysiology. Lancet. 1991; 337(8753):1321-4. DOI: 10.1016/0140-6736(91)92989-f. View

Goldman-Rakic P . The physiological approach: functional architecture of working memory and disordered cognition in schizophrenia. Biol Psychiatry. 1999; 46(5):650-61. DOI: 10.1016/s0006-3223(99)00130-4. View

Emborg M, Ma S, Mufson E, Levey A, Taylor M, Brown W . Age-related declines in nigral neuronal function correlate with motor impairments in rhesus monkeys. J Comp Neurol. 1998; 401(2):253-65. View

Chaudhuri K, Healy D, Schapira A . Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol. 2006; 5(3):235-45. DOI: 10.1016/S1474-4422(06)70373-8. View

Date I, Felten D, Felten S . Long-term effect of MPTP in the mouse brain in relation to aging: neurochemical and immunocytochemical analysis. Brain Res. 1990; 519(1-2):266-76. DOI: 10.1016/0006-8993(90)90088-s. View

10.

Guttman M, Boileau I, Warsh J, Saint-Cyr J, Ginovart N, McCluskey T . Brain serotonin transporter binding in non-depressed patients with Parkinson's disease. Eur J Neurol. 2007; 14(5):523-8. DOI: 10.1111/j.1468-1331.2007.01727.x. View

11.

Kish S, Shannak K, Rajput A, Deck J, Hornykiewicz O . Aging produces a specific pattern of striatal dopamine loss: implications for the etiology of idiopathic Parkinson's disease. J Neurochem. 1992; 58(2):642-8. DOI: 10.1111/j.1471-4159.1992.tb09766.x. View

12.

Mizoguchi K, Shoji H, Tanaka Y, Tabira T . Orbitofrontal dopaminergic dysfunction causes age-related impairment of reversal learning in rats. Neuroscience. 2010; 170(4):1110-9. DOI: 10.1016/j.neuroscience.2010.08.037. View

13.

Muslimovic D, Post B, Speelman J, Schmand B . Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology. 2005; 65(8):1239-45. DOI: 10.1212/01.wnl.0000180516.69442.95. View

14.

Hallman H, Olson L, Jonsson G . Neurotoxicity of the meperidine analogue N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on brain catecholamine neurons in the mouse. Eur J Pharmacol. 1984; 97(1-2):133-6. DOI: 10.1016/0014-2999(84)90521-1. View

15.

Haapaniemi T, Ahonen A, Torniainen P, Sotaniemi K, Myllyla V . [123I]beta-CIT SPECT demonstrates decreased brain dopamine and serotonin transporter levels in untreated parkinsonian patients. Mov Disord. 2001; 16(1):124-30. DOI: 10.1002/1531-8257(200101)16:1<124::aid-mds1007>3.0.co;2-r. View

16.

Kubanis P, Zornetzer S . Age-related behavioral and neurobiological changes: a review with an emphasis on memory. Behav Neural Biol. 1981; 31(2):115-72. DOI: 10.1016/s0163-1047(81)91195-x. View

17.

Gaspar P, Berger B, Febvret A, Vigny A, Henry J . Catecholamine innervation of the human cerebral cortex as revealed by comparative immunohistochemistry of tyrosine hydroxylase and dopamine-beta-hydroxylase. J Comp Neurol. 1989; 279(2):249-71. DOI: 10.1002/cne.902790208. View

18.

Thiruchelvam M, McCormack A, Richfield E, Baggs R, Tank A, Di Monte D . Age-related irreversible progressive nigrostriatal dopaminergic neurotoxicity in the paraquat and maneb model of the Parkinson's disease phenotype. Eur J Neurosci. 2003; 18(3):589-600. DOI: 10.1046/j.1460-9568.2003.02781.x. View

19.

Deutch A, Cameron D . Pharmacological characterization of dopamine systems in the nucleus accumbens core and shell. Neuroscience. 1992; 46(1):49-56. DOI: 10.1016/0306-4522(92)90007-o. View

20.

Dubois B, Pillon B . Cognitive deficits in Parkinson's disease. J Neurol. 1997; 244(1):2-8. DOI: 10.1007/pl00007725. View