The effect of adrenalectomy on the circadian variation in the rate of kindled seizure development

Weiss, Gerald K.; Lucero, Kristen; Fernandez, Michael; Karnaze, Dean S.; Castillo, Natalie

doi:10.1016/0006-8993(93)91686-m

Cited by 23 publications

(12 citation statements)

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“…A great deal of evidence already implicates CORT in the mechanism connecting stress in adulthood to epileptogenesis [49]: elevating CORT augments epileptogenesis and seizures in several animal models [7], [8], [9], [13], [50], [51], [52], [53], an effect reversed by antagonist of glucocorticoid and mineralocorticoid receptors [8]; whereas kindling is slowed in adrenalectomised or hypophysectomised rats [10], [11], [12], [13]. Thus, a direct effect of the enhanced CORT release post-seizures is a strong candidate explanation of the accelerated kindling epileptogenesis in MS exposed rats.…”

Section: Discussionmentioning

confidence: 99%

“…For stressors in adult life, studies are consistent in reporting that stress or stress mediators enhance epileptogenesis in experimental models [6]. For example, administering exogenous corticosterone (CORT) aggravates kindling epileptogenesis [7], [8], [9], an effect reversed using antagonists of glucocorticoid and mineralocorticoid receptors [8]; and kindling is slowed in adrenalectomised or hypophysectomised rats [10], [11], [12], [13]. Recently it has become increasingly clear that stress in early life can result in enduring vulnerability to epileptogenesis in adult animals [14], [15], [16], however, experimental data about mechanisms underlying such effects remain sparse.…”

Section: Introductionmentioning

confidence: 98%

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Early Life Stress Enhancement of Limbic Epileptogenesis in Adult Rats: Mechanistic Insights

et al. 2011

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BackgroundExposure to early postnatal stress is known to hasten the progression of kindling epileptogenesis in adult rats. Despite the significance of this for understanding mesial temporal lobe epilepsy (MTLE) and its associated psychopathology, research findings regarding underlying mechanisms are sparse. Of several possibilities, one important candidate mechanism is early life ‘programming’ of the hypothalamic-pituitary-adrenal (HPA) axis by postnatal stress. Elevated corticosterone (CORT) in turn has consequences for neurogenesis and cell death relevant to epileptogenesis. Here we tested the hypotheses that MS would augment seizure-related corticosterone (CORT) release and enhance neuroplastic changes in the hippocampus.Methodology/Principal FindingsEight-week old Wistar rats, previously exposed on postnatal days 2–14 to either maternal separation stress (MS) or control brief early handling (EH), underwent rapid amygdala kindling. We measured seizure-induced serum CORT levels and post-kindling neurogenesis (using BrdU). Three weeks post-kindling, rats were euthanized for histology of the hippocampal CA3c region (pyramidal cell counts) and dentate gyrus (DG) (to count BrdU-labelled cells and measure mossy fibre sprouting). As in our previous studies, rats exposed to MS had accelerated kindling rates in adulthood. Female MS rats had heightened CORT responses during and after kindling (p<0.05), with a similar trend in males. In both sexes total CA3c pyramidal cell numbers were reduced in MS vs. EH rats post-kindling (p = 0.002). Dentate granule cell neurogenesis in female rats was significantly increased post-kindling in MS vs. EH rats.Conclusions/SignificanceThese data demonstrate that early life stress results in enduring enhancement of HPA axis responses to limbic seizures, with increased hippocampal CA3c cell loss and augmented neurogenesis, in a sex-dependent pattern. This implicates important candidate mechanisms through which early life stress may promote vulnerability to limbic epileptogenesis in rats as well as to human MTLE and its associated psychiatric disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Early Life Stress Enhancement of Limbic Epileptogenesis in Adult Rats: Mechanistic Insights

et al. 2011

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“…Our data regarding the rate of hippocampal kindling extend earlier behavioural observations on amygdala kindling in Lewis and Fisher (Weiss et al . 1993a,b). The CORT level that circulates in the blood may be a critical factor, as behavioural signs of epilepsy were not significantly changed when we treated animals with a lower dose of CORT (20 mg/day; n = 11 animals, unpublished observation).…”

Section: Discussionmentioning

confidence: 99%

Episodic corticosterone treatment accelerates kindling epileptogenesis and triggers long‐term changes in hippocampal CA1 cells, in the fully kindled state

Karst

Kloet

Joëls

1999

Eur J of Neuroscience

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We tested the effect of episodic (approximately 10 days) corticosterone treatment on: (i) behavioural symptoms during kindling epileptogenesis; and (ii) electrical activity in the CA1 hippocampal area during epileptogenesis, and later on, in the fully kindled state. Male rats received a corticosterone-releasing pellet (100 mg/day) shortly before kindling was started, resulting in elevated hormone levels during the early and middle stages of epileptogenesis. The appearance of moderate behavioural signs of epilepsy and severe tonic-clonic seizures was significantly accelerated in corticosterone-treated animals compared to placebo controls. During epileptogenesis, corticosterone treatment did not affect the amplitude and paired-pulse characteristics of in vivo-recorded CA1 field responses, or the duration of the afterdischarge following tetanic stimulation of the Schaffer collaterals. However, other properties of CA1 cells studied in vitro, in the fully kindled state, were altered by the earlier episodic corticosterone treatment. Thus, in kindled rats, the amplitude of the population spike in the CA1 area was significantly enhanced after prior exposure to high corticosterone levels. Prior episodic steroid treatment resulted furthermore in a significantly increased amplitude of voltage-gated Ca currents, in kindled rats. At that time, corticosterone levels of animals which had received a corticosterone-releasing pellet earlier were no longer elevated compared to the placebo controls; the corticosteroid-treated rats did also not differ from the controls with respect to the mRNA expression levels for the two corticosteroid receptor subtypes in the hippocampus. The data suggest that exposure of animals to a period of stressful experiences during a critical phase in epileptogenesis could impose lasting deleterious effects on the course of epilepsy, even when CORT levels have been normalized again.

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“…Similar observations were made in animal models of epilepsy. For example, rats are more susceptible to amygdala kindling–induced epileptogenesis during subjective night (i.e., during lights on when the animals are least active, Weiss et al., 1993). In animal models of limbic epilepsy (induced by electrical stimulation of the hippocampus), spontaneous seizures are more frequent during subjective night (Bertram & Cornett, 1994;Quigg et al., 2000), a rhythm that persists under conditions of constant darkness (Quigg et al., 2000).…”

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confidence: 99%

Ketogenic diet treatment abolishes seizure periodicity and improves diurnal rhythmicity in epileptic Kcna1‐null mice

et al. 2009

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Summary Introduction Seizures are known to perturb circadian rhythms in humans as well as in animal models of epilepsy. However, it is unknown whether treatment of the underlying epilepsy restores normal biological rhythms. We asked whether: (1) seizure activity is characterized by diurnal rhythmicity; (2) chronically epileptic mice exhibit impaired activity-rest rhythms; and (3) treatment with the anticonvulsant ketogenic diet (KD) improves such perturbations. Methods Chronically epileptic Kcna1-null mice were fed either a standard diet or KD for 4 wks and subjected to continuous video-EEG and actigraphy monitoring for 3–5 days to assess seizure activity and rest-activity cycles. Results Seizure activity in Kcna1-null mice demonstrated diurnal rhythmicity, peaking at zeitgeber (ZT) 2.30±1.52. Activity-rest rhythms of epileptic mice were significantly disrupted. Whereas locomotor activity for wild-type mice peaked at ZT15.45±0.28 (ZT14:26–ZT16:51), peak activity of epileptic mice was more unpredictable, occurring over a 12.4hr range (ZT06:33–ZT18:57). In 6 of 9 epileptic mice, peak activity was delayed to ZT17.42±0.38, while peak activity was advanced to ZT10.00±1.26 in the remaining mice. Treatment with the KD abolished seizure periodicity and restored the activity-rest rhythm to values resembling those of wild-type mice (i.e. activity peaking at ZT16.73±0.67). Conclusions Kcna1-null mice experience seizures with 24-hr periodicity and impaired circadian behavior. KD reduces the number and periodicity of seizures and restores normal behavioral rhythms, suggesting that this non-pharmacological therapy may benefit biological rhythm disturbances in epileptic patients.

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The effect of adrenalectomy on the circadian variation in the rate of kindled seizure development

Cited by 23 publications

References 24 publications

Early Life Stress Enhancement of Limbic Epileptogenesis in Adult Rats: Mechanistic Insights

Early Life Stress Enhancement of Limbic Epileptogenesis in Adult Rats: Mechanistic Insights

Episodic corticosterone treatment accelerates kindling epileptogenesis and triggers long‐term changes in hippocampal CA1 cells, in the fully kindled state

Ketogenic diet treatment abolishes seizure periodicity and improves diurnal rhythmicity in epileptic Kcna1‐null mice

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