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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Abstract

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
Pages113-113
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
https://www.ans.org.au/resources/past-ans-conferences/57-past-ans-conferences (Link to conference abstracts)

Conference

Conference33rd Annual Meeting of the Australasian Neuroscience Society
Abbreviated titleNeuroscience
CountryAustralia
CityMelbourne
Period03/02/1306/02/13
Internet address

Fingerprint

Tremor
Hyperalgesia
Livestock
Hyperesthesia
Large-Conductance Calcium-Activated Potassium Channels
Lolium
Exploratory Behavior
Hypesthesia
Avidin
Purkinje Cells
Potassium Channels
Memory Disorders
Horseradish Peroxidase
Ataxia
Biotin
Dimethyl Sulfoxide
Amygdala
Alkaloids
Cerebellum
Cognition

Grant Number

  • 0000004673

Cite this

Combs, M., Quinn, J., Hamlin, A., & Rogers, G. (2013). Lolitrem B Intoxication Activates Neuronal Stress Pathways. 113-113. Poster session presented at 33rd Annual Meeting of the Australasian Neuroscience Society, Melbourne, Australia.
Combs, Martin ; Quinn, Jane ; Hamlin, Adam ; Rogers, Gill. / Lolitrem B Intoxication Activates Neuronal Stress Pathways. Poster session presented at 33rd Annual Meeting of the Australasian Neuroscience Society, Melbourne, Australia.1 p.
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abstract = "Lolitrem B is an indole–diterpenoid alkaloid toxin foundprimarily in perennial ryegrass. It is a potent inhibitor of large conductanceCa+ activated potassium (BK) channels. Ingestion of toxin causingcerebellar ataxia, tremor and Purkinje cell lesions has been extensivelyreported in grazing livestock. However, it has been suggested that amore widespread syndrome exists which includes anxiety, hypaesthesia,allodynia and cognitive dysfunction. This study used behavioural testingto assess cognitive function and c-Fos immunohistochemistry todetermine the level of activation in neuronal stress pathways followingacute lolitrem B exposure in the mouse. Methods: Adult mice wereinjected with lolitrem B (2mg/kg, IP) (n=12) or vehicle (DMSO) (n=12).Tremor was analysed using a pressure sensor and ADI PowerLabTManalyser. Spatial memory and learning, object recognition, and motorfunction were tested using the AnyMazeTM system. Additionally, at threehours post injection four mice from each group were anaesthetisedand transcardially perfused with 4{\%} paraformaldehyde. Brains weresectioned at 40μm and c-Fos immunoreactivity was revealed usingthe avidin-biotin-horseradish peroxidase technique. Results: Analysisconfirmed tremor in the range of 11-17Hz at one hour and increasing to18-25Hz by three hours, peaking at nine hours. A single dose of lolitremB did not induce spatial learning or memory deficits despite appearing toinduce short term abnormalities in normal exploratory behaviour. Countsof c-Fos-IR nuclei revealed a significant increase in the nucleus tractussolitarius, ventromedial medulla, parabrachial nucleus, central amygdala,and paraventricular hypothalamus following acute lolitrem exposure. Noc-Fos-IR was detected within the cerebellum. Conclusion: LolitremB induced a pattern of c-Fos immunoreactivity that is consistent withprevious clinical and experimental observations of intoxication inducinganxiety, allodynia and hyperaesthesia in production livestock.",
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Combs, M, Quinn, J, Hamlin, A & Rogers, G 2013, 'Lolitrem B Intoxication Activates Neuronal Stress Pathways' 33rd Annual Meeting of the Australasian Neuroscience Society, Melbourne, Australia, 03/02/13 - 06/02/13, pp. 113-113.

Lolitrem B Intoxication Activates Neuronal Stress Pathways. / Combs, Martin; Quinn, Jane; Hamlin, Adam; Rogers, Gill.

2013. 113-113 Poster session presented at 33rd Annual Meeting of the Australasian Neuroscience Society, Melbourne, Australia.

Research output: Other contribution to conferencePoster

TY - CONF

T1 - Lolitrem B Intoxication Activates Neuronal Stress Pathways

AU - Combs, Martin

AU - Quinn, Jane

AU - Hamlin, Adam

AU - Rogers, Gill

PY - 2013/2/2

Y1 - 2013/2/2

N2 - Lolitrem B is an indole–diterpenoid alkaloid toxin foundprimarily in perennial ryegrass. It is a potent inhibitor of large conductanceCa+ activated potassium (BK) channels. Ingestion of toxin causingcerebellar ataxia, tremor and Purkinje cell lesions has been extensivelyreported in grazing livestock. However, it has been suggested that amore widespread syndrome exists which includes anxiety, hypaesthesia,allodynia and cognitive dysfunction. This study used behavioural testingto assess cognitive function and c-Fos immunohistochemistry todetermine the level of activation in neuronal stress pathways followingacute lolitrem B exposure in the mouse. Methods: Adult mice wereinjected with lolitrem B (2mg/kg, IP) (n=12) or vehicle (DMSO) (n=12).Tremor was analysed using a pressure sensor and ADI PowerLabTManalyser. Spatial memory and learning, object recognition, and motorfunction were tested using the AnyMazeTM system. Additionally, at threehours post injection four mice from each group were anaesthetisedand transcardially perfused with 4% paraformaldehyde. Brains weresectioned at 40μm and c-Fos immunoreactivity was revealed usingthe avidin-biotin-horseradish peroxidase technique. Results: Analysisconfirmed tremor in the range of 11-17Hz at one hour and increasing to18-25Hz by three hours, peaking at nine hours. A single dose of lolitremB did not induce spatial learning or memory deficits despite appearing toinduce short term abnormalities in normal exploratory behaviour. Countsof c-Fos-IR nuclei revealed a significant increase in the nucleus tractussolitarius, ventromedial medulla, parabrachial nucleus, central amygdala,and paraventricular hypothalamus following acute lolitrem exposure. Noc-Fos-IR was detected within the cerebellum. Conclusion: LolitremB induced a pattern of c-Fos immunoreactivity that is consistent withprevious clinical and experimental observations of intoxication inducinganxiety, allodynia and hyperaesthesia in production livestock.

AB - Lolitrem B is an indole–diterpenoid alkaloid toxin foundprimarily in perennial ryegrass. It is a potent inhibitor of large conductanceCa+ activated potassium (BK) channels. Ingestion of toxin causingcerebellar ataxia, tremor and Purkinje cell lesions has been extensivelyreported in grazing livestock. However, it has been suggested that amore widespread syndrome exists which includes anxiety, hypaesthesia,allodynia and cognitive dysfunction. This study used behavioural testingto assess cognitive function and c-Fos immunohistochemistry todetermine the level of activation in neuronal stress pathways followingacute lolitrem B exposure in the mouse. Methods: Adult mice wereinjected with lolitrem B (2mg/kg, IP) (n=12) or vehicle (DMSO) (n=12).Tremor was analysed using a pressure sensor and ADI PowerLabTManalyser. Spatial memory and learning, object recognition, and motorfunction were tested using the AnyMazeTM system. Additionally, at threehours post injection four mice from each group were anaesthetisedand transcardially perfused with 4% paraformaldehyde. Brains weresectioned at 40μm and c-Fos immunoreactivity was revealed usingthe avidin-biotin-horseradish peroxidase technique. Results: Analysisconfirmed tremor in the range of 11-17Hz at one hour and increasing to18-25Hz by three hours, peaking at nine hours. A single dose of lolitremB did not induce spatial learning or memory deficits despite appearing toinduce short term abnormalities in normal exploratory behaviour. Countsof c-Fos-IR nuclei revealed a significant increase in the nucleus tractussolitarius, ventromedial medulla, parabrachial nucleus, central amygdala,and paraventricular hypothalamus following acute lolitrem exposure. Noc-Fos-IR was detected within the cerebellum. Conclusion: LolitremB induced a pattern of c-Fos immunoreactivity that is consistent withprevious clinical and experimental observations of intoxication inducinganxiety, allodynia and hyperaesthesia in production livestock.

M3 - Poster

SP - 113

EP - 113

ER -

Combs M, Quinn J, Hamlin A, Rogers G. Lolitrem B Intoxication Activates Neuronal Stress Pathways. 2013. Poster session presented at 33rd Annual Meeting of the Australasian Neuroscience Society, Melbourne, Australia.