Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022:271:379-400.
doi: 10.1007/164_2021_444.

The Kappa Opioid Receptor System in Temporal Lobe Epilepsy

Luca Zangrandi  1   2   3   4 , Christoph Schwarzer  5
Affiliations

The Kappa Opioid Receptor System in Temporal Lobe Epilepsy

Luca Zangrandi et al. Handb Exp Pharmacol. 2022.

Abstract

Temporal lobe epilepsy is considered to be one of the most common and severe forms of focal epilepsies. Patients frequently develop cognitive deficits and emotional blunting along progression of the disease. The high incidence of refractoriness to antiepileptic drugs and a frequent lack of admissibility to surgery pose an unmet medical challenge. In the urgent quest for novel treatment strategies, neuropeptides and their receptors are interesting candidates. However, their therapeutic potential has not yet been fully exploited. This chapter focuses on the functional role of the dynorphins (Dyns) and the kappa opioid receptor (KOR) system in temporal lobe epilepsy and the hippocampus.Genetic polymorphisms in the prepro-dynorphin (pDyn) gene causing lower levels of Dyns in humans and pDyn gene knockout in mice increase the risk to develop epilepsy. This suggests a role of Dyns and KOR as modulators of neuronal excitability. Indeed, KOR agonists induce inhibition of presynaptic neurotransmitter release, as well as postsynaptic hyperpolarization in glutamatergic neurons, both producing anticonvulsant effects.The development of new approaches to modulate the complex KOR signalling cascade (e.g. biased agonism and gene therapy) opens up new exciting therapeutic opportunities with regard to seizure control and epilepsy. Potential adverse side effects of KOR agonists may be minimized through functional selectivity or locally restricted treatment. Preclinical data suggest a high potential of such approaches to control seizures.

Keywords: Excitability; Hippocampus; Seizures; Temporal lobe epilepsy.

PubMed Disclaimer

References

    1. Agostinho AS, Mietzsch M, Zangrandi L, Kmiec I, Mutti A, Kraus L, Fidzinski P, Schneider UC, Holtkamp M, Heilbronn R, Schwarzer C (2019) Dynorphin-based “release on demand” gene therapy for drug resistant temporal lobe epilepsy. EMBO Mol Med 11(10):1–16. https://doi.org/10.15252/emmm.201809963 - DOI
    1. Amaral DG, Scharfman HE, Lavenex P (2007) The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies). pp 3–790. https://doi.org/10.1016/S0079-6123(07)63001-5
    1. Asadi-Pooya AA, Stewart GR, Abrams DJ, Sharan A (2017) Prevalence and incidence of drug-resistant mesial temporal lobe epilepsy in the United States. World Neurosurg 99:662–666. https://doi.org/10.1016/j.wneu.2016.12.074 - DOI - PubMed
    1. Babb TL, Brown WJ, Pretorius J, Davenport C, Lieb JP, Crandall PH (1984) Temporal lobe volumetric cell densities in temporal lobe epilepsy. Epilepsia 25(6):729–740. https://doi.org/10.1111/j.1528-1157.1984.tb03484.x - DOI - PubMed
    1. Barbarosie M, Avoli M (1997) CA3-driven hippocampal-entorhinal loop controls rather than sustains in vitro limbic seizures. J Neurosci 17(23):9308–9314. https://doi.org/10.1523/JNEUROSCI.17-23-09308.1997 - DOI - PubMed - PMC

LinkOut - more resources