Domoic acid induced status epilepticus promotes aggressive behavior in rats

“…It is also evident that domoic acid can trigger a separate process of epileptogeneis, which, over a latent “silent” period of weeks to months, causes a disease state of progressive recurrent seizures and behavioral abnormalities [8,9,10,11]. We now define domoic acid epileptic disease as distinct consequence of domoic acid poisoning that occurs in the absence of domoic acid.…”

Section: Concept Of Domoic Acid Epileptic Diseasementioning

confidence: 99%

“…Several weeks after the status epilepticus, two main manifestations are seen: rats develop a progressive state of seizures similar to epilepsy or atypical aggressive behaviors, with the majority of rats showing various degrees of both responses [11]. Spontaneous recurrent seizures occurred in 94% of rats within six months with an average latent period of five weeks [10].…”

Section: Domoic Acid Epileptic Diseasementioning

confidence: 99%

Domoic Acid Epileptic Disease

Ramsdell

Gulland

2014

Marine Drugs

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Domoic acid epileptic disease is characterized by spontaneous recurrent seizures weeks to months after domoic acid exposure. The potential for this disease was first recognized in a human case study of temporal lobe epilepsy after the 1987 amnesic shellfish-poisoning event in Quebec, and was characterized as a chronic epileptic syndrome in California sea lions through investigation of a series of domoic acid poisoning cases between 1998 and 2006. The sea lion study provided a breadth of insight into clinical presentations, unusual behaviors, brain pathology, and epidemiology. A rat model that replicates key observations of the chronic epileptic syndrome in sea lions has been applied to identify the progression of the epileptic disease state, its relationship to behavioral manifestations, and to define the neural systems involved in these behavioral disorders. Here, we present the concept of domoic acid epileptic disease as a delayed manifestation of domoic acid poisoning and review the state of knowledge for this disease state in affected humans and sea lions. We discuss causative mechanisms and neural underpinnings of disease maturation revealed by the rat model to present the concept for olfactory origin of an epileptic disease; triggered in dendodendritic synapases of the olfactory bulb and maturing in the olfactory cortex. We conclude with updated information on populations at risk, medical diagnosis, treatment, and prognosis.

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“…California sea lions exposed to levels of DA that are not acutely lethal can display diminished spatial memory [7], blunted habituation to auditory stimuli [8], heightened aggression [9], highly repetitive behaviors [10], and abnormal locomotion in both water [11] and land [9]. Experimental studies that involve the administation of low doses of DA to adult rodents show that exposed subjects express hypomobility [12], impaired spatial learning [13] (Petrie et al, 1992), aggression [14], and significantly increased stereotypic behaviors [15]. …”

Section: Introductionmentioning

confidence: 99%

Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional connectivity MRI

Mills

Pearce

Khan

et al. 2016

Behavioural Brain Research

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Domoic acid (DA) is a toxin produced by marine algae and known primarily for its role in isolated outbreaks of Amnestic Shellfish Poisoning and for the damage it inflicts on marine mammals, particularly California sea lions. Lethal effects of DA are often preceded by seizures and coma. Exposure to DA during development can result in subtle and highly persistent effects on brain development and include behavioral changes that resemble diagnostic features of schizophrenia and anomalies in social behavior we believe are relevant to autism spectrum disorder (ASD). To more fully examine this hypothesis, we chose to examine adolescent mice exposed in utero to DA for endpoints relevant to ASD, specifically changes in social behavior and network structure, the latter measured by resting state functional connectivity (rsfcMRI). We found that male offspring exposed in utero to DA expressed reproducible declines in social interaction and atypical patterns of functional connectivity in the anterior cingulate, a region of the default mode network that is critical for social functioning. We also found disruptions in global topology in regions involved in the processing of reward, social, and sensory experiences. Finally, we found that DA exposed males expressed a pattern of local over-connectivity. These anomalies in brain connectivity bear resemblance to connectivity patterns in ASD and help validate DA-exposed mice as a model of this mental disability.

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Domoic acid induced status epilepticus promotes aggressive behavior in rats

Cited by 16 publications

References 34 publications

Adverse Outcome Pathway on binding of agonists to ionotropic glutamate receptors in adult brain leading to excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment

Adverse Outcome Pathway on binding of agonists to ionotropic glutamate receptors in adult brain leading to excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment

Domoic Acid Epileptic Disease

Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional connectivity MRI

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