Early life stress as an influence on limbic epilepsy: a hypothesis whose time has come?

Koe, Amelia S.; Jones, Nigel C.; Salzberg, Michael

doi:10.3389/neuro.08.024.2009

Cited by 61 publications

(57 citation statements)

References 216 publications

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“…Indeed, the results obtained when brain morphological changes were prevented suggest that all treatments, even nonpharmacological treatments, suppressing residual traces in the hippocampus and the amygdala should also suppress vulnerability to the development of depressive disorders. Such changes may be extended to other diseases in which life stressor events predispose individuals to develop, for instance, epilepsy (Koe et al, 2009) or schizophrenia (Cannon et al, 2003). Figure 8.…”

Section: Discussionmentioning

confidence: 99%

Vulnerability to Depression: From Brain Neuroplasticity to Identification of Biomarkers

Blugeot¹,

Rivat²,

Bouvier³

et al. 2011

J. Neurosci.

161

147

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A stressful event increases the risk of developing depression later in life, but the possible predisposing factors remain unknown. Our study aims to characterize latent vulnerability traits underlying the development of depressive disorders in adult animals. Four weeks after a priming stressful event, serum corticosterone concentration returned to control values in all animals, whereas the other biological parameters returned to basal level in only 58% of animals (called nonvulnerable). In contrast, 42% of animals displayed persistent decreased serum and hippocampus BDNF concentrations, reduced hippocampal volume and neurogenesis, CA3 dendritic retraction and decrease in spine density, as well as amygdala neuron hypertrophy, constituting latent vulnerability traits to depression. In this group, called vulnerable, a subsequent mild stress evoked a rise of serum corticosterone levels and a "depressive" phenotype, in contrast to nonvulnerable animals. Intracerebroventricular administration of 7,8-dihydroxyflavone, a selective TrkB receptor agonist, dampened the development of the "depressive" phenotype. Our results thus characterize the presence of latent vulnerability traits that underlie the emergence of depression and identify the association of low BDNF with normal corticosterone serum concentrations as a predictive biomarker of vulnerability to depression.

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Section: Discussionmentioning

confidence: 99%

Vulnerability to Depression: From Brain Neuroplasticity to Identification of Biomarkers

Blugeot¹,

Rivat²,

Bouvier³

et al. 2011

J. Neurosci.

161

147

View full text Add to dashboard Cite

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“…A recent review (Koe et al 2009) found seven rodent studies reporting long-term effects of early life stress on epilepsy-relevant outcomes (e.g., seizure threshold, kindling rate). Of these, two studies employed prenatal stressors (e.g., restraint), four employed postnatal stressors (maternal separation, neonatal isolation (from both mother and siblings), cross-fostering), and one study used both.…”

Section: Focal Limbic Epilepsymentioning

confidence: 99%

“…This in turn has motivated an immense body of experimental work in animal models, mainly rodent and primate studies, showing fairly consistent, often large effects of stressors and stress mediators on brain, often enduring well into later adult life. We and others have shown that early life stress increases vulnerability to limbic epilepsy in adult life (Koe et al 2009). In early life stress research, a variety of experimental models are employed, such as prenatal glucocorticoid administration, postnatal separation of pups from dams (or from both dams and siblings), or restriction of the dam's access to nesting material (Sanchez et al 2001;Weinstock 2008), and much is known about intervening mechanisms, although vastly more remains to be understood McEwen 2008;Oitzl et al 2010).…”

Section: Introductionmentioning

confidence: 96%

Electrophysiological insights into the enduring effects of early life stress on the brain

et al. 2010

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Increasing evidence links exposure to stress early in life to long-term alterations in brain function, which in turn have been linked to a range of psychiatric and neurological disorders in humans. Electrophysiological approaches to studying these causal pathways have been relatively underexploited. Effects of early life stress on neuronal electrophysiological properties offer a set of potential mechanisms for these susceptibilities, notably in the case of epilepsy. Thus, we review experimental evidence for altered cellular and circuit electrophysiology resulting from exposure to early life stress. Much of this work focuses on limbic long-term potentiation, but other studies address alterations in electrophysiological properties of ion channels, neurotransmitter systems, and the autonomic nervous system. We discuss mechanisms which may mediate these effects, including influences of early life stress on key components of brain synaptic transmission, particularly glutamate, GABA and 5-HT receptors, and influences on neuroplasticity (primarily neurogenesis and synaptic density) and on neuronal network activity. The existing literature, although small, provides strong evidence that early life stress induces enduring, often robust effects on a range of electrophysiological properties, suggesting further study of enduring effects of early life stress employing electrophysiological methods and concepts will be productive in illuminating disease pathophysiology.

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“…The vulnerable population was identified to have low serum levels of brain-derived neurotrophic factor (BDNF) and increased circulating levels of corticosterone. Treating animals with the BDNF analog, 7-8-dihydroxyflavone (7, or the antidepressant imipramine during the "second hit" prevented the elevations in corticosterone and the adverse behavioral consequences, including depression-like behavior and anhedonia. These data suggest that low levels of BDNF play a critical role in allostatic load in adult animals and vulnerability to depression.…”

Section: Primed For Problems: Stress Confers Vulnerability To Epilepsmentioning

confidence: 99%

“…For example, maternal separation induces long-lasting effects on seizure susceptibility and increased propensity for epileptogenesis (for a review, see [7]). A recent study demonstrated that early life stress due to maternal separation exacerbated the seizure-induced elevations in corticosterone levels, reduced seizure threshold, and increased seizure severity (4).…”

mentioning

confidence: 99%

Primed for Problems: Stress Confers Vulnerability to Epilepsy and Associated Comorbidities

Maguire¹

2015

Epilepsy Curr

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CommentaryAllostasis is defined as the process by which the body responds to stressors in order to regain homeostasis, which involves proper functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Allostatic load refers to the pathophysiological consequences of dealing with excessive, prolonged, or unresolved stress and is also thought to involve abnormalities in the functioning of the HPA axis (for a review, see [1]). There has been a great deal of speculation regarding the role of allostatic load in disease, and numerous correlational studies have attempted to investigate the pathological implications of allostatic load. However, as the authors state in the highlighted manuscript, "causality remains to be determined. "Through a series of studies, this group attempts to directly link allostatic load to pathophysiological outcomes. They previously demonstrated that social stress induces an allostatic load and vulnerability for depression in a subset of rats when faced with a subsequent, novel stressor (2). The authors suggest a "double-hit scenario" where the initial social defeat stressor (first hit) sensitizes a subset of animals, making them vulnerable to additional stressors (second hit). In the currently highlighted manuscript, Becker et al. extend these findings to investigate the pathophysiological implications of allostatic load acquired by exposure to a social defeat stress on epilepsy and associated comorbidities. This study, which is the basis of this Commentary, proposes that previous exposure to a stressor, which itself is insufficient to induce depression-like behavior, can alter epileptogenesis and predispose a subset of animals for associated comorbidities, including depression-like behaviors and cognitive impairments.Stress has been implicated in epilepsy given that the majority of patients report that stress either triggers or worsens their seizures (3). Consistent with a role of stress in epilepsy, the currently highlighted study demonstrates that in a subset of rats (~50%) previous exposure to social stress results in a reduced threshold to induce status epilepticus (SE), a shorter latency to SE, and increased seizure frequency in chronically epileptic rats (see Figure 3 in the Becker et al. article). These results alone are not surprising, given the fact that stress has been demonstrated to increase seizure susceptibility in a variety of experimental epilepsy models (3) and has recently been demonstrated to accelerate epileptogenesis (4). Further, administration of exogenous stress hormones-including corticosterone and corticotropin-releasing hormone (CRH)-have been shown to exert proconvulsant actions in numerous experimental models of epilepsy (for a review, see [5]). However, these studies focus on how acute and prolonged stress or exposure to glucocorticoids can alter neuronal excitability and seizure susceptibility with little regard to how changes in the functioning of the HPA axis may influence epilepsy.A large body of evidence suggests that early life stress can reprogram the H...

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Early life stress as an influence on limbic epilepsy: a hypothesis whose time has come?

Cited by 61 publications

References 216 publications

Vulnerability to Depression: From Brain Neuroplasticity to Identification of Biomarkers

Vulnerability to Depression: From Brain Neuroplasticity to Identification of Biomarkers

Electrophysiological insights into the enduring effects of early life stress on the brain

Primed for Problems: Stress Confers Vulnerability to Epilepsy and Associated Comorbidities

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