title: Differential susceptibility of astrocytic and neuronal function to 3-chloropropanediol in the rat inferior colliculus.
abstract: We have previously shown that systemic administration of S(+)3-chloropropanediol (3-CPD) produces a morphological loss of astrocytes in specific nuclei of the rodent brain that precedes loss of both neurones and endothelial tight junctions. Here, we have evaluated the differential susceptibility of neuronal and astrocytic function to 3-CPD, in order to see if this parallels the morphological selectivity. To do this, we have developed an in vivo method for monitoring astrocyte function over time by giving hourly 20-min bolus challenge exposures to ammonia via an implanted microdialysis probe and measuring the resulting transient increases in the extracellular glutamine : glutamate ratio. These challenge ammonia exposures evoked a stable response for at least 5 h when the probe was implanted in the rat inferior colliculus, but caused no behavioural response or morphological damage. Although 3-CPD produced a rapid and sustained abolition of the ammonia response within 2 h, the field potential response of inferior collicular neurones to sound fell significantly to 75.0 ± 3.9% pre-dose at up to 8 h but then fell markedly, reaching 20.5 ± 3.7% at 2 days. Blood flow in the inferior colliculus also showed only late changes, increasing substantially at 2 days. Astrocyte damage at the EM level was seen from 3 h, followed by loss of astrocytes from 18 h to a minimum of 7 ± 10% control at 3 days. The rapid abolition of the ammonia response suggests that in addition to selective astrocyte death, 3-CPD also produces an earlier impairment of astrocyte function that precedes loss of neuronal function. This initial functional selectivity of 3-CPD provides a potential investigative tool in neurochemical studies of astrocyte-neuronal interactions.
authors.affiliation: School of Biomedical Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK. ambrown@nottingham.ac.uk
authors.forename: Angus M
authors.initials: AM
authors.lastname: Brown
authors.forename: John
authors.initials: J
authors.lastname: Skamarauskas
authors.forename: Timothy
authors.initials: T
authors.lastname: Lister
authors.forename: Ameneh
authors.initials: A
authors.lastname: Madjd
authors.forename: David E
authors.initials: DE
authors.lastname: Ray
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000641:Ammonia / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000648:ultrastructure; D039481:CD11b Antigen / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000379:methods; D005072:Evoked Potentials, Auditory / Q000187:drug effects / Q000502:physiology; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D007245:Inferior Colliculi / Q000098:blood supply / Q000166:cytology* / Q000502:physiology; D008297:Male; D017551:Microdialysis / Q000379:methods; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D011571:Psychoacoustics; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D000517:alpha-Chlorohydrin / Q000494:pharmacology*
chemical_list: D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D005973:Glutamine; D018698:Glutamic Acid; D000641:Ammonia; D000517:alpha-Chlorohydrin