In situ hybridization for detection of nocardial 16S rRNA: Reactivity within intracellular inclusions in experimentally infected cynomolgus monkeys - And in Lewy body-containing human brain specimens

Gail Chapman, Blaine L. Beaman, David A. Loeffler, Dianne M. Camp, Edward F. Domino, Dennis W Dickson, William G. Ellis, Ibsen Chen, Susan E. Bachus, Peter A. LeWitt

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Our previous studies found that experimental infection of BALB/c mice with the Gram-positive bacterium Nocardia asteroides induced a parkinsonian-type syndrome with levodopa-responsive movement abnormalities, loss of nigrostriatal dopaminergic neurons, depletion of striatal dopamine, and intraneuronal inclusions in the substantia nigra (SN) with an appearance similar to Lewy bodies. In the present study, an in situ hybridization technique was developed to detect nocardial 16S ribosomal RNA (rRNA), using a Nocardia-specific probe (B77). Cerebral cortical specimens from cynomolgus monkeys were examined for the presence of nocardial RNA 48 h, 3.5 months, and 1 year after experimental infection with N. asteroides. Hybridization reactions were detected within Nocardia-like structures 48 h after infection and within intracellular inclusion bodies (immunoreactive for α-synuclein and ubiquitin) in one of two 3.5-month-infected monkeys. The in situ hybridization procedure was then applied in a blinded fashion to 24 human SN specimens with Lewy bodies and 11 human SN specimens without Lewy bodies (including five normal controls). Hybridization reactions were detected in nine Lewy body-containing specimens and none of the others. Reactivity was limited to inclusions with the appearance of Lewy bodies, with the exception of one specimen in which intracellular reactivity was also observed in Nocardia-like structures. These results suggest a possible association between Nocardia and neurodegenerative disorders in which Lewy bodies are present.

Original languageEnglish (US)
Pages (from-to)715-725
Number of pages11
JournalExperimental Neurology
Volume184
Issue number2
DOIs
StatePublished - Dec 2003

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16S Ribosomal RNA
Lewy Bodies
Macaca fascicularis
In Situ Hybridization
Nocardia
Brain
Substantia Nigra
Nocardia asteroides
Synucleins
Infection
Corpus Striatum
Dopaminergic Neurons
Inclusion Bodies
Parkinsonian Disorders
Levodopa
Gram-Positive Bacteria
Ubiquitin
Neurodegenerative Diseases
Haplorhini
Dopamine

Keywords

  • Dementia with Lewy bodies
  • In situ hybridization
  • Lewy bodies
  • Neurodegeneration
  • Nocardia
  • Parkinson's disease

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

In situ hybridization for detection of nocardial 16S rRNA : Reactivity within intracellular inclusions in experimentally infected cynomolgus monkeys - And in Lewy body-containing human brain specimens. / Chapman, Gail; Beaman, Blaine L.; Loeffler, David A.; Camp, Dianne M.; Domino, Edward F.; Dickson, Dennis W; Ellis, William G.; Chen, Ibsen; Bachus, Susan E.; LeWitt, Peter A.

In: Experimental Neurology, Vol. 184, No. 2, 12.2003, p. 715-725.

Research output: Contribution to journalArticle

Chapman, Gail ; Beaman, Blaine L. ; Loeffler, David A. ; Camp, Dianne M. ; Domino, Edward F. ; Dickson, Dennis W ; Ellis, William G. ; Chen, Ibsen ; Bachus, Susan E. ; LeWitt, Peter A. / In situ hybridization for detection of nocardial 16S rRNA : Reactivity within intracellular inclusions in experimentally infected cynomolgus monkeys - And in Lewy body-containing human brain specimens. In: Experimental Neurology. 2003 ; Vol. 184, No. 2. pp. 715-725.
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T2 - Reactivity within intracellular inclusions in experimentally infected cynomolgus monkeys - And in Lewy body-containing human brain specimens

AU - Chapman, Gail

AU - Beaman, Blaine L.

AU - Loeffler, David A.

AU - Camp, Dianne M.

AU - Domino, Edward F.

AU - Dickson, Dennis W

AU - Ellis, William G.

AU - Chen, Ibsen

AU - Bachus, Susan E.

AU - LeWitt, Peter A.

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AB - Our previous studies found that experimental infection of BALB/c mice with the Gram-positive bacterium Nocardia asteroides induced a parkinsonian-type syndrome with levodopa-responsive movement abnormalities, loss of nigrostriatal dopaminergic neurons, depletion of striatal dopamine, and intraneuronal inclusions in the substantia nigra (SN) with an appearance similar to Lewy bodies. In the present study, an in situ hybridization technique was developed to detect nocardial 16S ribosomal RNA (rRNA), using a Nocardia-specific probe (B77). Cerebral cortical specimens from cynomolgus monkeys were examined for the presence of nocardial RNA 48 h, 3.5 months, and 1 year after experimental infection with N. asteroides. Hybridization reactions were detected within Nocardia-like structures 48 h after infection and within intracellular inclusion bodies (immunoreactive for α-synuclein and ubiquitin) in one of two 3.5-month-infected monkeys. The in situ hybridization procedure was then applied in a blinded fashion to 24 human SN specimens with Lewy bodies and 11 human SN specimens without Lewy bodies (including five normal controls). Hybridization reactions were detected in nine Lewy body-containing specimens and none of the others. Reactivity was limited to inclusions with the appearance of Lewy bodies, with the exception of one specimen in which intracellular reactivity was also observed in Nocardia-like structures. These results suggest a possible association between Nocardia and neurodegenerative disorders in which Lewy bodies are present.

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