The effects of age and lipopolysaccharide (LPS)-mediated peripheral inflammation on numbers of central catecholaminergic neurons

P. R. Mouton, B. Kelley-Bell, D. Tweedie, E. L. Spangler, E. Perez, O. D. Carlson, R. G. Short, R. deCabo, J. Chang, D. K. Ingram, Y. Li, N. H. Greig

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24 Scopus citations

Abstract

Parkinson's disease (PD), an age-related movement disorder, is characterized by severe catecholaminergic neuron loss in the substantia nigra pars compacta (SNPC)-ventral tegmental area (VTA) and locus coeruleus (LC). To assess the stability of these central catecholaminergic neurons following an acute episode of severe inflammation, 6 to 22 month old C57/Bl6 mice received a maximally tolerated dose of lipopolysaccharide (LPS) followed by euthanasia 2 hours later to assay peak levels of peripheral and central cytokines; and, 14 weeks later for computerized stereology of tyrosine hydroxylase-immunopositive (tyrosine hydroxylase-positive [TH+]) neurons in the SNPC-VTA and LC. Two hours after LPS, cytokine levels varied in an age-related manner, with the greatest peripheral and central elevations in old and young mice, respectively. Severe inflammation failed to cause loss of TH+ neurons in SNPC-VTA or LC; however, there was an age-related decline in these TH+ neurons in LPS-treated and control groups. Thus, unknown mechanisms in the B6 mouse brain appear to protect against catecholaminergic neuron loss following an acute episode of severe inflammation, while catecholaminergic neuron loss occurs during normal aging.

Original languageEnglish
Pages (from-to)423.e27-423.e36
JournalNeurobiology of Aging
Volume33
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • Age-related neuron loss
  • Computerized stereology
  • Neuroinflammation
  • Parkinsonism
  • Stereologer
  • Substantia nigra
  • Ventral tegmental area

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