Central administration of p234, kisspeptin antagonist, but not kisspeptin-10, reduces the power of epileptiform activity and slow EEG waves in male rats.
Kalkan. Ömer Faruk ÖF; Şahin. Zafer Z; Aktaş. Osman O; Yildirim. Abdulhamit A; Aydin Abidin. Selcen S; Özyaşar. Ali Faruk AF; Uzun. İbrahim İ; Abidin. İsmail İ
Key Findings
- Injecting 4-AP caused seizure-like brain activity in all rats.
- Giving kisspeptin-10 after seizures started did not change the seizures or brain wave power.
- Giving the kisspeptin blocker p234 before the seizure trigger reduced seizure activity and lowered slow EEG bands (delta and theta).
Practical Outcomes
- For biohackers, this study doesn't provide a usable protocol or dosage for humans. It suggests that blocking kisspeptin receptors might calm over‑excited neurons, but there's no evidence it works safely in people or offers benefits for longevity, metabolism, or performance.
Summary
In rats, a drug that blocks kisspeptin (called p234) lowered brain wave activity and reduced seizure-like spikes when it was given before a seizure trigger, but the natural kisspeptin peptide itself had no effect. This was a lab study on brain activity, not a human trial.
Abstract
We aimed to investigate the effects of central kisspeptin-10 and p234 administration on basal brain activity and epilepsy-like conditions induced by 4-aminopyridine (4-AP), as well as their roles in the electrocorticogram (ECoG) power spectrum and EEG waves. Thirty-five male Wistar rats were divided into five groups: sham,4-AP (2.5 mg/kg i.p.), kisspeptin-10 post-treatment (200 pmoli.c.v.), p234 post-treatment (1 nmol i.c.v.), and p234 pre-treatment (1 nmol i.c.v.). We performed 70 minutes of recordings (10 min baseline) for all groups under ketamine/xylazine (90/10 mg/kg) anesthesia. In the post-treatment groups, kisspeptin-10 or p234 injections were administered 20 minutes after epilepsy induction. In the pre-treatment group, p234 was injected after baseline recordings. Following a 20-minute pre-treatment period, 4-AP was administered. 4-AP alone induced epileptiform activity in all animals, reaching apeak after 30 minutes. Neither kisspeptin-10 nor p234 post-treatment affected 4-AP-induced epileptiform activity (<i>p</i> > 0.05). However, p234 pre-treatment reduced epileptiform activity (<i>p</i> < 0.05). Additionally, kisspeptin-10 did not alter the spectral analysis of the EEG bands or the power of the ECoG (<i>p</i> > 0.05). In contrast, p234 reduced the power of the ECoG and the slow bands (delta and theta) (<i>p</i> < 0.05). We conclude that p234 pre-treatment has an inhibitory effect on neuronal excitability and epileptiform activity in the neocortex.
Study Information
pubmed
2025
2025-01-21T00:00:00.000Z
10.1080/01616412.2025.2456293
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