Effect of Aging on Tyrosine Hydroxylase Protein Content and the Relative Number of Dopamine Nerve Terminals in Human Caudate

Marina Wolf, P. A. LeWitt, M. J. Bannon, L. J. Dragovic, G. Kapatos

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Abstract: This study examined the effect of aging on the relative number of dopamine (DA) nerve terminals in human caudate nucleus, their content of tyrosine hydroxylase (TH) protein, and the relative abundance of TH monomers with different molecular weights. Preliminary studies on brain tissue cryopreservation, performed with rat striatum, indicated that intact synaptosomes can be prepared from fresh tissue slowly frozen in 0.32 M sucrose with 5% dimethyl sulfoxide and then thawed rapidly prior to synaptosome preparation. Synaptosomes were prepared in this manner from postmortem caudate nucleus tissue obtained from normal humans 1 month to 63 years of age. To determine the relative number of DA nerve terminals for each individual, dopaminergic synaptosomes were selectively labeled with a monoclonal antibody to TH and quantified by fluorescence‐activated cell sorting. To determine the relative amount of TH protein for each individual, the concentration of TH protein in the same synaptosomal preparations was determined using immunoblots. Our results suggest that caudate TH levels plateau soon after birth and tend to remain relatively stable during aging, since no changes in either the relative number of TH‐containing nerve terminals or the concentration of TH protein were found in subjects 15–63 years of age. In light of previous studies showing an age‐related loss of DA cell bodies, these findings suggest that remaining DA neurons compensate to maintain caudate levels of TH protein and TH‐containing nerve terminals. Immunoblot studies identified three forms of TH monomer (60.6, 61.7, and 65.1 kDa), indicating that mRNAs coding for high molecular mass forms of TH may be actively translated in human brain. No age‐related differences in the relative abundance of these forms were found.

Original languageEnglish (US)
Pages (from-to)1191-1200
Number of pages10
JournalJournal of Neurochemistry
Volume56
Issue number4
DOIs
StatePublished - Jan 1 1991
Externally publishedYes

Fingerprint

Tyrosine 3-Monooxygenase
Dopamine
Aging of materials
Synaptosomes
Proteins
Caudate Nucleus
Tissue
Brain
Monomers
Cells
Dopaminergic Neurons
Cryopreservation
Molecular mass
Dimethyl Sulfoxide
Sorting
Neurons
Sucrose
Rats
Molecular Weight
Molecular weight

Keywords

  • Aging
  • Dopamine
  • Flow cytometry
  • Human caudate nucleus
  • Synaptosomes

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Effect of Aging on Tyrosine Hydroxylase Protein Content and the Relative Number of Dopamine Nerve Terminals in Human Caudate. / Wolf, Marina; LeWitt, P. A.; Bannon, M. J.; Dragovic, L. J.; Kapatos, G.

In: Journal of Neurochemistry, Vol. 56, No. 4, 01.01.1991, p. 1191-1200.

Research output: Contribution to journalArticle

Wolf, Marina ; LeWitt, P. A. ; Bannon, M. J. ; Dragovic, L. J. ; Kapatos, G. / Effect of Aging on Tyrosine Hydroxylase Protein Content and the Relative Number of Dopamine Nerve Terminals in Human Caudate. In: Journal of Neurochemistry. 1991 ; Vol. 56, No. 4. pp. 1191-1200.
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