Adrenergic innervation of the brain plays a key role in the regulation of sleep and epilepsy - the Institute of Higher Nervous Activity and Neurophysiology

Two main types of adrenergic receptors (alpha and beta) and many subtypes have been described in the human and animal brain. Alpha2-adrenergic receptors deserve special attention because they are involved in the modulation of sleep and absence epilepsy. In 2023, a group of young scientists under the guidance of a senior mentor, Dr. Sc. E.Yu. Sitnikova began research on the adrenergic mechanisms of sleep and epilepsy, the results of which were published in the International Journal of Molecular Science and Frontiers in Neurology [1, 2, 3]. Therapeutic doses of alpha2-adrenergic agonists (eg, dexmedetomidine) are known to have a sedative effect and induce drug-induced sleep in humans and animals. These drugs in low doses cause generalized peak-wave activity on the electroencephalogram, i.e. manifestation of absence epilepsy in rats with a genetic predisposition to this disease (WAG/Rij) [1, 2, 3]. Thus, a single injection of dexmedetomidine at a dose of about 0.005 mg/kg increased absence epilepsy in WAG/Rij rats (a genetic model of absence epilepsy) up to the onset of status epilepticus in individuals with severe absence epilepsy [2], but did not cause absence epilepsy. de novo epilepsy in asymptomatic rats [1, 2]. Dexmedetomidine is regularly used in clinical practice, and can be used in low doses to diagnose latent forms of absence epilepsy [1]. The high risk of provoking absence status should be taken into account when using alpha2-adrenergic receptor agonists in patients with absence epilepsy or with a genetic predisposition to this disease [1].

Based on an analysis of our own and literature data, a new concept of targeted pharmacotherapy of absence epilepsy using alpha2B-adrenergic receptor antagonists was put forward [1, 3].

Sitnikova E. Adrenergic mechanisms of absence status epilepticus Front. Neurol. 2023 14: 1298310. DOI: 10.3389/fneur.2023.1298310
Sitnikova E., Pupikina M., Rutskova E. Alpha2 Adrenergic Modulation of Spike-Wave Epilepsy: Experimental Study of Pro-Epileptic and Sedative Effects of Dexmedetomidine. International Journal of Molecular Sciences. 2023. 24(11): 9445. DOI: 10.3390/ijms24119445 .
Sitnikova E., Rutskova E., Smirnov K. Alpha2-Adrenergic Receptors as a Pharmacological Target for Spike-Wave Epilepsy. International Journal of Molecular Sciences. 2023. 24(2):1477. DOI: 10.3390/ijms24021477.