Toluene exposure during maturation of intraocular brain tissue transplants: Alterations of host and graft cerebellar Purkinje neuron function and sensitivity to norepinephrine

A. C. Granholm, G. A. Gerhardt, E. Moore, M. Eriksdotter-Nilsson, P. Nylén, A. C. Johnson, A. Henschen, M. A. Shirley, M. R. Palmer, B. J. Hoffer, G. Höglund, L. Olson

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


The effects of chronic toluene exposure on central neurons were examined using syngeneic grafts into the anterior chamber of the eye. Young adult albino rats with intraocular brain transplants inhaled toluene (1000 ppm) for 9 weeks starting at the time of transplantation, or from Week 8 to 17 after the graft was placed in oculo. Control animals were exposed to room air during the same intervals. Toluene treatment during development did not affect general growth or morphology of any of the brain areas examined. The distribution of neurofilament or glial fibrillary acidic protein immunoreactivity was similar in the experimental group and control group as well. Extracellular recordings of cerebellar Purkinje neurons showed a significantly reduced spontaneous firing rate, of 15-25%, both in intraocular transplants and in cerebellum in situ in toluene exposed animals. Postsynaptic sensitivity of intraocular and in situ Purkinje neurons to norepinephrine (NE) was evaluated. Purkinje neurons in transplants exposed to toluene during development were markedly supersensitive to superfused NE as compared to controls, while neither Purkinje neurons in mature cerebellar grafts nor cerebellum in situ showed any effects of the toluene treatment on NE sensitivity. The tissue content of NE in transplants exposed to toluene during maturation, evaluated with high-performance liquid chromatography coupled with electrochemical detection, was greater than that in the control grafts. Moreover, the content of free (3-methoxy-4-hydroxyphenyl) ethylene glycol (MHPG) was increased in both transplant and host cerebellum after toluene exposure. Taken together, these data indicate that toluene exposure during development of cerebellar grafts in oculo causes changes in postsynaptic noradrenergic sensitivity as well as decreased spontaneous activity of Purkinje neurons. Toluene exposure of adult cerebellum in situ or in oculo appears to decrease the Purkinje neuron discharge rate and increase NE turnover, but has no marked effect on postsynaptic NE sensitivity.

Original languageEnglish
Pages (from-to)296-304
Number of pages9
JournalToxicology and Applied Pharmacology
Issue number2
StatePublished - Nov 1988

Bibliographical note

Funding Information:
This work was supported by the Swedish Work Envi-ronment Health Fund and USPHS Grants ES 020 I IAA and AC 06434. Dr. Granholm was funded by a fellowship from the Daniel Heumann Foundation for Spinal Cord Research. We thank Karin LundstrGmer. Carina Ohlsson. Barhro Standwerth. Maud Hagman. Lotta Jo-hansson. and Gunilla Linder for skillful technical assistance. Ida Engqvist is acknowledged for expert secretarial help.

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


Dive into the research topics of 'Toluene exposure during maturation of intraocular brain tissue transplants: Alterations of host and graft cerebellar Purkinje neuron function and sensitivity to norepinephrine'. Together they form a unique fingerprint.

Cite this