Decreased density of lymphocyte benzodiazepine receptors in drug-resistant epileptic patients

Ferrarese, Carlo; Tortorella, Rachele; Bogliun, G.; Beghi, Ettore; Cogliati, Tiziana; Zoia, Chiara Paola; Passoni, Davide; Frattola, L.

doi:10.1016/s0920-1211(97)01035-8

Cited by 6 publications

(4 citation statements)

References 16 publications

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“…Kappa opioid receptor agonists have been shown to be anticonvulsant (Loacker et al, 2007;Manocha et al, 2003;Zangrandi and Schwarzer, 2022). Peripheral benzodiazepine receptor ligands have also shown potential relationships toward seizure control (Ferrarese et al, 1997;Shiotani et al, 2000) as have 5-HT 1A receptors (Gharib et al, 2018;Pelz et al, 2017;Sapa et al, 2014;Waszkielewicz et al, 2015) (Gharib et al, 2018;Pelz et al, 2017;Sapa et al, 2014;Waszkielewicz et al, 2015). However, the selectivity of these compounds over these targets is one piece of evidence that these ancillary actions are not necessary for the anticonvulsant activity of these compounds.…”

Section: Discussionmentioning

confidence: 99%

Structural Analogs of the GABAkine KRM-II-81 Are Orally Bioavailable Anticonvulsants without Sedation

Pandey

Divović

Rashid

et al. 2023

J Pharmacol Exp Ther

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Section: Discussionmentioning

confidence: 99%

Structural Analogs of the GABAkine KRM-II-81 Are Orally Bioavailable Anticonvulsants without Sedation

Pandey

Divović

Rashid

et al. 2023

J Pharmacol Exp Ther

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“…Apart from damaged brain areas, platelets also show increased PBR ligand binding in patients with Alzheimer's disease (Bidder et al 1990) and the same is true for platelets, neutrophils, and lymphocytes in patients with epilepsy (Johnson et al 1992;Larkin et al 1993;Ferrarese et al 1996;Caldiroli et al 1997). A positive role of PBR may be inferred from the observation that carbamazepine up-regulates the binding of [ 3 H]PK 11195 to platelets of epileptic patients (Weizman et al 1987), while drug-resistant epileptic patients are characterized by low PBR density on blood mononuclear cells (Ferrarese et al 1997). In animal studies, enhancement of PBR abundance also concurs with excitotoxic, neurotoxic, traumatic, and ischemic brain damage (for a review see Veenman and Gavish 2000).…”

mentioning

confidence: 99%

“…A positive role of PBR may be inferred from the observation that carbamazepine up‐regulates the binding of [ 3 H]PK 11195 to platelets of epileptic patients (Weizman et al . 1987), while drug‐resistant epileptic patients are characterized by low PBR density on blood mononuclear cells (Ferrarese et al . 1997).…”

mentioning

confidence: 99%

PK 11195 attenuates kainic acid‐induced seizures and alterations in peripheral‐type benzodiazepine receptor (PBR) protein components in the rat brain

Veenman

Leschiner

Spanier

et al. 2002

Journal of Neurochemistry

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Peripheral-type benzodiazepine receptors (PBR) are located in glial cells in the brain and in peripheral tissues. Mitochondria form the primary location for PBR. Functional PBR appear to require at least three components: an isoquinoline binding protein, a voltage-dependent anion channel, and an adenine nucleotide carrier. In the present study, rats received intraperitoneal kainic acid injections, which are known to cause seizures, neurodegeneration, hyperactivity, gliosis, and a fivefold increase in PBR ligand binding density in the hippocampus. In the forebrain of control rats, hippocampal voltagedependent anion channel and adenine nucleotide carrier abundance was relatively low, while isoquinoline binding protein abundance did not differ between hippocampus and the rest of the forebrain. One week after kainic acid injection, isoquinoline binding protein abundance was increased more than 20-fold in the hippocampal mitochondrial fraction. No significant changes were detected regarding hippocampal voltage-dependent anion channel and adenine nucleotide carrier abundance. Pre-treatment with the isoquinoline PK11195, a specific PBR ligand, attenuated the occurrence of seizures, hyperactivity, and increases in isoquinoline binding protein levels in the hippocampus, which usually follow kainic acid application. These data suggest that isoquinoline binding protein may be involved in these effects of kainic acid injections.

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“…DBI plasma levels have been assessed before in epileptic patients finding elevated values in adult generalized epilepsy and in drug-resistant both paediatric and adult patients [21]. A DBI alteration in this patient population was analogously hypothesized based on our group's previous report of a differential expression of PBR in PBMC obtained from drug-treated epileptic patients and of a significantly lower receptor density in drug-resistant patients when compared to newly diagnosed patients and to normal age-related controls [24,25]. Interestingly, DBI can modulate the GABAergic tone both by the biosynthesis of neurosteroids (able to directly change the activity of GABA A receptor-associated chloride channels and, more generally, to modulate gene expression), and by its direct action as a GABA A inverse agonist [26].…”

Section: Discussionmentioning

confidence: 55%

Diazepam Binding Inhibitor and Dehydroepiandrosterone Sulphate Plasma Levels in Borderline Personality Disorder Adolescents

Conti

Nacinovich²,

Bomba³

et al. 2013

Neuropsychobiology

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Background: Borderline personality disorder (BPD) patients display a complex and heterogeneous clinical phenotype that plausibly implies variable underlying pathogenic mechanisms. A dysregulation of peripheral benzodiazepine receptors has previously been shown in BPD peripheral tissues, implying possible alterations of its ligand, the diazepam binding inhibitor (DBI) or of the downstream products of its activation, i.e. neuroactive steroids. Methods: The aim of this work consisted in assessing, by ELISA, fasting plasma levels of DBI and dehydroepiandrosterone sulphate (DHEA-S), including cortisol and the cortisol-to-DHEA-S molar ratio (CDR), in 17 BPD adolescents versus 13 healthy controls, testing the possibility that clinical scales related to depressive or anxious traits (CDI, STAI-Y) or to disease severity (BPDCL) might be associated with a selective dysregulation of these parameters. Results: DBI plasma levels were unchanged, while DHEA-S ones were significantly increased (approx. 70%) and the CDR decreased in BPD patients. No meaningful correlations with clinical variables emerged. Conclusion: Our results indicate that a dysfunction of the neurosteroid system might be operative in BPD in spite of unchanged DBI plasma levels and that DHEA-S might represent a generalized trait marker for the altered stress response that is associated with this disorder.

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Decreased density of lymphocyte benzodiazepine receptors in drug-resistant epileptic patients

Cited by 6 publications

References 16 publications

Structural Analogs of the GABAkine KRM-II-81 Are Orally Bioavailable Anticonvulsants without Sedation

Structural Analogs of the GABAkine KRM-II-81 Are Orally Bioavailable Anticonvulsants without Sedation

PK 11195 attenuates kainic acid‐induced seizures and alterations in peripheral‐type benzodiazepine receptor (PBR) protein components in the rat brain

Diazepam Binding Inhibitor and Dehydroepiandrosterone Sulphate Plasma Levels in Borderline Personality Disorder Adolescents

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