title: Toluene exposure during maturation of intraocular brain tissue transplants: alterations of host and graft cerebellar Purkinje neuron function and sensitivity to norepinephrine.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Colorado Health Sciences Center, Denver.
authors.forename: A C
authors.initials: AC
authors.lastname: Granholm
authors.forename: G A
authors.initials: GA
authors.lastname: Gerhardt
authors.forename: E
authors.initials: E
authors.lastname: Moore
authors.forename: M
authors.initials: M
authors.lastname: Eriksdotter-Nilsson
authors.forename: P
authors.initials: P
authors.lastname: Nylén
authors.forename: A C
authors.initials: AC
authors.lastname: Johnson
authors.forename: A
authors.initials: A
authors.lastname: Henschen
authors.forename: M A
authors.initials: MA
authors.lastname: Shirley
authors.forename: M R
authors.initials: MR
authors.lastname: Palmer
authors.forename: B J
authors.initials: BJ
authors.lastname: Hoffer
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001921:Brain / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004594:Electrophysiology; D005123:Eye; D005260:Female; D006087:Graft vs Host Reaction; D009417:Nerve Tissue / Q000637:transplantation*; D009474:Neurons / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011689:Purkinje Cells / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014050:Toluene / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D014050:Toluene; D009638:Norepinephrine