Neuropeptide Y suppresses absence seizures in a genetic rat model

Stroud, Leanne M.; O’Brien, Terence J.; Jupp, Bianca; Wallengren, Charlott; Morris, Margaret J.

doi:10.1016/j.brainres.2004.11.022

Cited by 46 publications

(43 citation statements)

References 26 publications

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“…Antiepileptic effect of ghrelin was also reported in an acute experimental epilepsy model in pentylenetetrazole-injected rats (Obay et al 2007). Neuropeptide Y (NPY) and g-aminobutyric acid (GABA) may be involved in the anticonvulsant effect of ghrelin because NPY and GABA exert antiepileptic effects in animal seizure models (Czapinski et al 2005, Stroud et al 2005 and ghrelin not only enhances NPY but also increases GABA-ergic activity in the brain (Cowley et al 2003). It is well known that a majority of epileptic seizures are due to an imbalance between the activities of inhibitory and excitatory neurotransmitters (Sharma et al 2007).…”

Section: Discussionmentioning

confidence: 97%

Ghrelin attenuates kainic acid-induced neuronal cell death in the mouse hippocampus

Lee¹,

Lim²,

Kim³

et al. 2010

Journal of Endocrinology

108

111

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Ghrelin is an endogenous ligand for GH secretagogue receptor type 1a (GHSR1a), and is produced and released mainly from the stomach. It has been recently demonstrated that ghrelin can function as a neuroprotective factor by inhibiting apoptotic pathways. Kainic acid (KA), an excitatory amino acid L-glutamate analog, causes neuronal death in the hippocampus; previous studies suggest that activated microglia and astrocytes actively participate in the pathogenesis of KA-induced hippocampal neurodegeneration. However, it is unclear whether ghrelin has neuroprotective effect in KA-induced hippocampal neurodegeneration. I.p. injection of KA produced typical neuronal cell death in the CA1 and CA3 pyramidal layers of the hippocampus, and the systemic administration of ghrelin significantly attenuated KA-induced neuronal cell death in these regions through the activation of GHSR1a. Ghrelin prevents KA-induced activation of microglia and astrocytes, and the expression of proinflammatory mediators tumor necrosis factor a, interleukin-1b, and cyclooxygenase-2. The inhibitory effect of ghrelin on the activation of microglia and astrocytes appears to be associated with the inhibition of matrix metalloproteinase-3 expression in damaged hippocampal neurons. Our data suggest that ghrelin has a therapeutic potential for suppressing KA-induced pathogenesis in the brain.

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Section: Discussionmentioning

confidence: 97%

Ghrelin attenuates kainic acid-induced neuronal cell death in the mouse hippocampus

Lee¹,

Lim²,

Kim³

et al. 2010

Journal of Endocrinology

108

111

View full text Add to dashboard Cite

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“…Our results underscore that NPY can function as an endogenous anticonvulsant in spike-wave seizures of absence epilepsy [2,23,25]. Understanding the modulatory action of NPY and specifying which Y receptors mediate a given effect contributes towards a better understanding of thalamic oscillations and may possibly highlight novel routes for treatment of absence seizures.…”

Section: Discussionmentioning

confidence: 52%

“…In the hippocampus, increased NPY expression is thought to be a compensatory effect of kindling and epileptogenesis [19,22,30,31], in vivo experiments in GEARS rats demonstrate that NPY suppresses absence seizures [23] and the anticonvulsant valproic acid has been proposed to act at least in part via an upregulation of NPY expression in hippocampus and nRt [2].…”

Section: Introductionmentioning

confidence: 99%

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NPY signaling through Y1 receptors modulates thalamic oscillations

2007

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Neuropeptide Y is the ligand of a family of G-protein coupled receptors (Y 1 to Y 6 ). In the thalamus, exogenous and endogenously released NPY can shorten the duration of thalamic oscillations in brain slices from P13 to P15 rats, an in vitro model of absence seizures. Here, we examine which Y receptors are involved in this modulation. Application of the Y 1 receptor agonist Leu 31 Pro 34 NPY caused a reversible reduction in the duration of thalamic oscillations (−26.6 +/− 7.8%), while the Y 2 receptor agonist peptideYY and the Y 5 receptor agonist BWX-46 did not exert a significant effect. No Y receptor agonist affected oscillation period. Application of antagonists of Y 1 , Y 2 and Y 5 receptors (BIBP3226, BIIE0246 and L152,806, respectively) produced results consistent with those obtained from agonists. BIBP3226 caused a reversible disinhibition, an effect that increases oscillation duration (18.2 +/− 9.7%) while BIIE0246 and L152,806 had no significant effect. Expression of NPY is limited to neurons in the reticular thalamic nucleus (nRt), but Y 1 receptors are expressed in both nRt and adjacent thalamic relay nuclei. Thus, intra-nRt or nRt to relay nucleus NPY release could cause Y 1 receptor mediated inhibition of thalamic oscillations.

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“…More recently, the role of new hormones in epilepsy like ghrelin and its modulation on GH and NPY has been investigated (Berilgen et al, 2006;Gallagher et al, 1984;Morrell, 2003;Obay et al, 2007;Quigg, 2002;Stroud et al, 2005). Overall, endocrine disorders related to epilepsy or antiepileptic drugs are a consequence of the influence of epileptogenic lesions, epilepsy or anticonvulsant medications on the endocrine control centers in the brain.…”

Section: Introductionmentioning

confidence: 99%