Lolitrem B Intoxication Activates Neuronal Stress Pathways

Martin Combs, Jane Quinn, Adam Hamlin, Gill Rogers

Research output: Other contribution to conferencePoster

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Lolitrem B is an indole–diterpenoid alkaloid toxin found
primarily in perennial ryegrass. It is a potent inhibitor of large conductance
Ca+ activated potassium (BK) channels. Ingestion of toxin causing
cerebellar ataxia, tremor and Purkinje cell lesions has been extensively
reported in grazing livestock. However, it has been suggested that a
more widespread syndrome exists which includes anxiety, hypaesthesia,
allodynia and cognitive dysfunction. This study used behavioural testing
to assess cognitive function and c-Fos immunohistochemistry to
determine the level of activation in neuronal stress pathways following
acute lolitrem B exposure in the mouse. Methods: Adult mice were
injected with lolitrem B (2mg/kg, IP) (n=12) or vehicle (DMSO) (n=12).
Tremor was analysed using a pressure sensor and ADI PowerLabTM
analyser. Spatial memory and learning, object recognition, and motor
function were tested using the AnyMazeTM system. Additionally, at three
hours post injection four mice from each group were anaesthetised
and transcardially perfused with 4% paraformaldehyde. Brains were
sectioned at 40μm and c-Fos immunoreactivity was revealed using
the avidin-biotin-horseradish peroxidase technique. Results: Analysis
confirmed tremor in the range of 11-17Hz at one hour and increasing to
18-25Hz by three hours, peaking at nine hours. A single dose of lolitrem
B did not induce spatial learning or memory deficits despite appearing to
induce short term abnormalities in normal exploratory behaviour. Counts
of c-Fos-IR nuclei revealed a significant increase in the nucleus tractus
solitarius, ventromedial medulla, parabrachial nucleus, central amygdala,
and paraventricular hypothalamus following acute lolitrem exposure. No
c-Fos-IR was detected within the cerebellum. Conclusion: Lolitrem
B induced a pattern of c-Fos immunoreactivity that is consistent with
previous clinical and experimental observations of intoxication inducing
anxiety, allodynia and hyperaesthesia in production livestock.
Original languageEnglish
Number of pages1
Publication statusPublished - 02 Feb 2013
Event33rd Annual Meeting of the Australasian Neuroscience Society: ANS 2013 - Melbourne Convention and Exhibition Centre, Melbourne, Australia
Duration: 03 Feb 201306 Feb 2013 (Link to conference abstracts)


Conference33rd Annual Meeting of the Australasian Neuroscience Society
Abbreviated titleNeuroscience
Internet address

Grant Number

  • 0000004673


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