Inhibition by thyrotropin-releasing hormone of epileptic seizures in spontaneously epileptic rats

Ujihara, Hisamitsu; Xie, Ruiqin; Sasa, Masashi; Ishihara, Kumatoshi; Fujita, Yasuhiko; Yoshimura, Mika; Kishimoto, Takuzo; Serikawa, Tadao; Yamada, Junzo; Takaori, Shuji

doi:10.1016/0014-2999(91)90403-d

Cited by 31 publications

(15 citation statements)

References 22 publications

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“…Importantly, clinical studies have identified TRH as an anticonvulsant in children with Lennox-Gastaut and West syndromes (Matsumoto et al, 1987;Takeuchi et al, 2001) and in animal models of epilepsy, including absence epilepsy (Ujihara et al, 1991;Momiyama et al, 1996). These likely represent central effects because, as also demonstrated for the sleep-modulating effects (Nishino et al, 1997), TRH doses sufficient to produce anticonvulsive protection do not significantly elevate peripheral thyroid hormone concentrations, and the anticonvulsant actions are not mimicked by activation of the thyroid axis (Nemeroff et al, 1975;Momiyama et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, prominent TRH receptor (TRHR) expression occurs in thalamic relay nuclei (Cao et al, 1998;Heuer et al, 2000;O'Dowd et al, 2000). Yet despite the documented presence of signaling components, a role for TRH within the thalamocortical circuitry remains to be determined; however, clinical and experimental reports suggest that both ep-ileptic discharge and sleep can be modulated by TRH (Nemeroff et al, 1975;Matsumoto et al, 1987;Ujihara et al, 1991;Momiyama et al, 1996;Nishino et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Excitatory Effects of Thyrotropin-Releasing Hormone in the Thalamus

Broberger¹,

McCormick²

2005

J. Neurosci.

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The activity of the thalamus is state dependent. During slow-wave sleep, rhythmic burst firing is prominent, whereas during waking or rapid eye movement sleep, tonic, single-spike activity dominates. These state-dependent changes result from the actions of modulatory neurotransmitters. In the present study, we investigated the functional and cellular effects of the neuropeptide thyrotropin-releasing hormone (TRH) on the spontaneously active ferret geniculate slice. This peptide and its receptors are prominently expressed in the thalamic network, yet the role of thalamic TRH remains obscure. Bath application of TRH resulted in a transient cessation of both spindle waves and the epileptiform slow oscillation induced by application of bicuculline. With intracellular recordings, TRH application to the GABAergic neurons of the perigeniculate (PGN) or thalamocortical cells in the lateral geniculate nucleus resulted in depolarization and increased membrane resistance. In perigeniculate neurons, this effect reversed near the reversal potential for K ϩ , suggesting that it is mediated by a decrease in K ϩ conductance. In thalamocortical cells, the TRH-induced depolarization was of sufficient amplitude to block the generation of rebound Ca 2ϩ spikes, whereas the even larger direct depolarization of PGN neurons transformed these cells from the burst to tonic, single-spike mode of action potential generation. Furthermore, application of TRH prominently enhanced the afterdepolarization that follows rebound Ca 2ϩ spikes, suggesting that this transmitter may also enhance Ca 2ϩ -activated nonspecific currents. These data suggest a novel role for TRH in the brain as an intrinsic regulator of thalamocortical network activity and provide a potential mechanism for the wake-promoting and anti-epileptic effects of this peptide.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Excitatory Effects of Thyrotropin-Releasing Hormone in the Thalamus

Broberger¹,

McCormick²

2005

J. Neurosci.

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“…TRH was anti-convulsant in experimental models of temporal [303,304] and absence epilepsies [305,306]. TRH is safe in children and effective in some cases of West syndrome and Lennox-Gastaut syndrome [307] and in progressive myoclonic epilepsy [308].…”

Section: Thyrotropin-releasing Hormonementioning

confidence: 99%

“…Some neuropeptides, e.g. NPY [28], dynorphin [139], TRH [305,306] are known to be involved in absence epilepsy, too. However, many other neuropeptides have not been thoroughly investigated in animal models of absence epilepsies.…”

Section: Comparison Of Neuropeptide Systems Regarding Their Role In Ementioning

confidence: 99%

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Dobolyi¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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Neuropeptides are signaling molecules participating in the modulation of synaptic transmission. Neuropeptides are stored in dense core synaptic vesicles, the release of which requires profound excitation. Only in the extracellular space, neuropeptides act on G-protein coupled receptors to exert a relatively slow action both pre-and postsynaptically. Consequently, neuropeptide modulators are ideal candidates to influence epileptic tissue overexcited during seizures. Indeed, a number of neuropeptides have been implicated in epilepsy and many of them are considered to have endogenous neuroprotective actions. Neuropeptides, present in the hippocampus, the most frequent focus of seizures in temporal lobe epilepsy, received the largest attention as potential anti-epileptic substances. Hippocampal neuropeptides, somatostatin, neuropeptide Y, galanin, dynorphin, enkephalin, substance P, cholecystokinin, vasoactive intestinal polypeptide, and some neuropeptides, which are also hormones such as ghrelin, angiotensins, corticotropin-releasing hormone, adrenocorticotropin, thyrotropin-releasing hormone, oxytocin and vasopressin involved in epilepsy are discussed in the review article. Oral application of neuropeptides as drugs is typically not efficient because of low bioavailability: rapid degradation and insufficient penetration through the blood-brain barrier. Recent progress in the development of non-peptide agonists and antagonists of neuropeptide receptors as well as gene therapeutic approaches leading to the local production of neuropeptides within the central nervous system will also be discussed.

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“…In addition, our preliminary experiments showed that both seizures were also inhibited by catecholamine-releasing drugs such as methamphetamine and thyrotropin-releasing hormone (TRH) and by dopamine receptor agonists such as apomorphine (Sasa et al, 19883;Ujihara et al, 1991).…”

mentioning

confidence: 97%

Decreased Dopamine and Increased Norepinephrine Levels in the Spontaneously Epileptic Rat, a Double Mutant Rat

et al. 1993

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Dopamine (DA) and norepinephrine (NE) brain levels and turnover rate were examined in the spontaneously epileptic rat (SER: zi/zi, tm/tm), a double mutant rat obtained by mating tremor heterozygotes (tm/+) with zitter homozygotes associated with epileptic seizures composed of spontaneously occurring tonic convulsion and absence-like seizure. DA and NE levels were also determined in age-matched male zitter, tremor and Kyo: Wistar rats. DA levels in caudate nucleus were significantly lower in adult age (10-12 weeks) SER, which showed epileptic seizures, and zitter rats than in adult Kyo: Wistar and tremor rats. DA levels in other areas such as thalamus-hypothalamus, midbrain, and pons medulla were not different among SER, zitter, tremor, and Kyo: Wistar rats at age 10-12 weeks. Except in cerebral cortex and hippocampus, there were no differences in brain DA levels between young seizure-free SER (age 5 weeks) and young Kyo: Wistar rats. Furthermore, the turnover rate of DA was significantly lower in caudate nucleus of adult SER than of Kyo: Wistar rat, whereas in pons-medulla there was no difference between the two strains. In contrast, NE levels in the thalamus-hypothalamus, midbrain, cerebellum and pons-medulla were higher in SER and zitter rats at age 10-12 weeks than in age-matched tremor and Kyo: Wistar rats. Higher NE levels were also observed in midbrain, cerebellum, and pons-medulla of young SER as compared with young Kyo: Wistar rats. Turnover rates of NE were significantly lower in pons-medulla and cerebellum of the adult SER than in those of Kyo: Wistar rat.(ABSTRACT TRUNCATED AT 250 WORDS)

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Inhibition by thyrotropin-releasing hormone of epileptic seizures in spontaneously epileptic rats

Cited by 31 publications

References 22 publications

Excitatory Effects of Thyrotropin-Releasing Hormone in the Thalamus

Excitatory Effects of Thyrotropin-Releasing Hormone in the Thalamus

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Decreased Dopamine and Increased Norepinephrine Levels in the Spontaneously Epileptic Rat, a Double Mutant Rat

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