Vasoactive intestinal polypeptide and its receptor changes in human temporal lobe epilepsy

Lanerolle, Nihal C. de; Günel, Murat; Sundaresan, S.; Shen, Miles; Brines, Michael; Spencer, Dennis D.

doi:10.1016/0006-8993(95)00365-w

Cited by 33 publications

(27 citation statements)

References 35 publications

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“…For example, NPY innervation shifts from being present primarily in the outer two thirds of the molecular layer in MaTLE tissue to filling the entire molecular layer in MTS with a dense fiber plexus, despite a loss of some of the NPY-immunoreactive cells in the hilus. Similar changes have also been reported for somatostatin (17)(18)(19). These peptides often colocalize with GABA (20), which suggests that the changes in peptide-immunoreactive fibers also reflect alterations in the GABAergic circuitry.…”

Section: Anatomy and Pathology Of The Human Mts Hippocampussupporting

confidence: 76%

Regulation of Excitability in the Epileptic Human Dentate Gyrus

Williamson

Patrylo

1999

Neuroscientist

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Numerous anatomical and physiological changes occur in the dentate gyrus of patients with medial temporal lobe sclerosis, a specific form of temporal lobe epilepsy. Although many of the reported changes are potentially proconvulsive, patients do not seize continuously. We hypothesize that neuromodulatory systems present in the epileptic dentate gyrus may help limit neuronal hyperexcitability and/or hypersynchronization. Three such systems are described in detail, including GABA, zinc, and adenosine. In addition, we briefly discuss several other modulatory systems that have not been studied extensively in the epileptic human hippocampus but that are also well suited to controlling neuronal excitability. NEUROSCIENTIST 5362- 370, 1999 Seizure disorders are among the most common and devastating neurological problems. Approximately 5% of the U.S. population that live to the age of 80 have a seizure disorder at some point in their lives (1). Epilepsy can result from a great diversity of underlying causes and its clinical manifestations can vary greatly based on the underlying etiology (e.g., tumors, trauma, or developmental anomalies) and on the cortical region involved. Medial temporal lobe epilepsy (TLE) is probably the most commonly studied of all the epilepsies, primarily because of the stereotyped pattern of clinical and pathological findings seen in patients with a subclass of TLE, medial temporal lobe sclerosis (MTS), and the inability to successfully treat these patients with the available antiepileptic compounds. MTS is a pathological definition first described in 1966 (2) and is characterized by extensive (6040%) cell loss in the CA1 and CA3 regions of the hippocampus and within the dentate hilus. Human MTS tissue has since been studied using a variety of techniques. These studies have been aided by the extensive body of literature on the anatomy and physiology of the rodent hippocampal formation.Clinically, MTS patients present with medically intractable seizures of temporal lobe origin. Its clinical evaluation has been described by a number of authors (3) and includes quantitative MRI analysis, neuropsychological evaluation for lobar-specific deficits, and continuous audio-visual EEG monitoring. The "classical" yalexdu).MTS patient has a history of neurological insult during childhood, often a febrile seizure, followed by a seizurefree period that can last for up to a decade, and the subsequent development of progressively intractable seizures. In general, MRI scans show unilateral hippocampal and temporal lobe atrophy on the side of seizure onset as determined by EEG analysis, with no evidence for structural lesions. Neuropsychological assessment shows that there are specific memory and functional deficits associated with MTS that also correlate to the side of seizure onset (4). When this constellation of clinical findings is present, anteromedial temporal lobectomy with hippocampectomy is associated with an 80 to 90% seizure-free outcome (5).A variety of structural lesions within the temporal lobe, in...

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Section: Anatomy and Pathology Of The Human Mts Hippocampussupporting

confidence: 76%

Regulation of Excitability in the Epileptic Human Dentate Gyrus

Williamson

Patrylo

1999

Neuroscientist

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“…The distributions of VIP and its receptors were fi rst reported in the hippocampus of patients with TLE [56] , and showed an increase in VIP receptors but no changes in the distribution pattern of VIP-IR neurons in mesial TLE patients. In regard to the role of VIP in human TLE, there are three hypotheses that may account for these changes [56] . The first is that VIP plays a role in the hyperexcitability of neurons in the hippocampal seizure focus.…”

Section: Neuropeptide-containing Interneurons and Epilepsymentioning

confidence: 97%

Dysfunction of hippocampal interneurons in epilepsy

Liu

et al. 2014

Neurosci. Bull.

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Gamma-amino-butyric acid (GABA)-containing interneurons are crucial to both development and function of the brain. Down-regulation of GABAergic inhibition may result in the generation of epileptiform activity. Loss, axonal sprouting, and dysfunction of interneurons are regarded as mechanisms involved in epileptogenesis. Recent evidence suggests that network connectivity and the properties of interneurons are responsible for excitatory-inhibitory neuronal circuits. The balance between excitation and inhibition in CA1 neuronal circuitry is considerably altered during epileptic changes. This review discusses interneuron diversity, the causes of interneuron dysfunction in epilepsy, and the possibility of using GABAergic neuronal progenitors for the treatment of epilepsy.

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“…VIP actions are exerted by G-protein coupled receptors VPAC1-R and VPAC2-R [198], which belong to class II of G-protein coupled receptors, recognize VIP and also the related neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP). These receptors were shown to be upregulated in hippocampal surgical samples of patients suffering from human temporal lobe epilepsy [206]. Some subtype-specific peptide agonists and antagonists for VIP receptors are available.…”

Section: Vasoactive Intestinal Peptidementioning

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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Vasoactive intestinal polypeptide and its receptor changes in human temporal lobe epilepsy

Cited by 33 publications

References 35 publications

Regulation of Excitability in the Epileptic Human Dentate Gyrus

Regulation of Excitability in the Epileptic Human Dentate Gyrus

Dysfunction of hippocampal interneurons in epilepsy

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

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