Recovery of hypothalamic tuberoinfundibular dopamine neurons from acute toxicant exposure is dependent upon protein synthesis and associated with an increase in parkin and ubiquitin carboxy-terminal hydrolase-L1 expression.

Neurotoxicology
Matthew BenskeyJ L Goudreau

Abstract

Hypothalamic tuberoinfundibular dopamine (TIDA) neurons remain unaffected in Parkinson disease (PD) while there is significant degeneration of midbrain nigrostriatal dopamine (NSDA) neurons. A similar pattern of susceptibility is observed in acute and chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse and rotenone rat models of degeneration. It is not known if the resistance of TIDA neurons is a constitutive or induced cell-autonomous phenotype for this unique subset of DA neurons. In the present study, treatment with a single injection of MPTP (20 mg/kg; s.c.) was employed to examine the response of TIDA versus NSDA neurons to acute injury. An acute single dose of MPTP caused an initial loss of DA from axon terminals of both TIDA and NSDA neurons, with recovery occurring solely in TIDA neurons by 16 h post-treatment. Initial loss of DA from axon terminals was dependent on a functional dopamine transporter (DAT) in NSDA neurons but DAT-independent in TIDA neurons. The active metabolite of MPTP, 1-methyl, 4-phenylpyradinium (MPP+), reached higher concentration and was eliminated slower in TIDA compared to NSDA neurons, which indicates that impaired toxicant bioactivation or distribution is an unlikely explanation ...Continue Reading

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Citations

May 29, 2012·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Tyrell J SimkinsBarbara L F Kaplan
Jul 14, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Olena Y GlushakovaStefania Mondello
Apr 20, 2016·Free Radical Biology & Medicine·Raquel Requejo-Aguilar, Juan P Bolaños
Mar 23, 2017·Journal of Chemical Neuroanatomy·Steven A LloydRyan A Shanks
Jan 10, 2018·Frontiers in Aging Neuroscience·Brittany M WinnerJohn L Goudreau
Aug 14, 2019·Scientific Reports·Lyudmila KovalchukeLloyd A Greene
Nov 29, 2021·Neurochemical Research·Yu-Min CaoQi-Yuan Fan

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