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Effect of des-tyrosine-gamma-endorphin on neocortical spike-and-wave spindling in DBA/2J mice
A Capasso1, L Sorrentino, A Di Giannuario
1School of Pharmacy, University of Salerno, Italy.
Abstract:
The effect of a beta-endorphin cleavage product devoid of opioid effects, des-tyrosine-gamma-endorphin (DT gamma E) on the neocortical spike-and-wave spindling episodes in the electrocorticogram (ECoG) of DBA/2J mice was studied. DT gamma E (0.01-1.0 mg/kg, i.p.) dose dependently reduced the spike-and-wave bursts duration. However, the low dose did not induce consistent modifications of the spike-and-wave bursts number while the dose of 0.1 and 1.0 mg/kg induced a progressive diminution. Furthermore, at all doses DT gamma E did not induce any alterations of the spike-and-wave bursts amplitude, frequency, and desynchronized activity when compared to the pre-drug period. These results indicate that this beta-endorphin fragment may affect brain excitability.
Insights
Des-tyrosine-gamma-endorphin (DT gamma E), a beta-endorphin fragment, reduced the duration of neocortical spike-and-wave episodes in mice. This suggests DT gamma E may influence brain excitability without opioid effects.
Area of Science:
- Neuroscience
- Pharmacology
- Endocrinology
Background:
- Beta-endorphin is a key opioid peptide involved in pain and stress responses.
- Opioid peptides can be cleaved into smaller fragments with distinct biological activities.
- Neocortical spike-and-wave discharges are characteristic of certain neurological conditions.
Purpose of the Study:
- To investigate the effects of des-tyrosine-gamma-endorphin (DT gamma E), a non-opioid beta-endorphin fragment, on electrocorticogram (ECoG) activity in DBA/2J mice.
- To determine if DT gamma E modulates neocortical spike-and-wave spindling episodes.
Main Methods:
- Administration of varying doses of DT gamma E (0.01-1.0 mg/kg, i.p.) to DBA/2J mice.
- Recording and analysis of neocortical electrocorticogram (ECoG) activity.
- Quantification of spike-and-wave burst duration, number, amplitude, frequency, and desynchronized activity.
Main Results:
- DT gamma E dose-dependently reduced the duration of neocortical spike-and-wave bursts.
- Higher doses (0.1 and 1.0 mg/kg) progressively diminished the number of spike-and-wave bursts.
- No significant alterations in burst amplitude, frequency, or desynchronized activity were observed.
Conclusions:
- Des-tyrosine-gamma-endorphin (DT gamma E) exhibits anticonvulsant-like properties by reducing the duration and number of spike-and-wave episodes.
- These effects occur independently of opioid receptor interactions, suggesting a novel mechanism of action.
- DT gamma E may represent a potential therapeutic agent for conditions characterized by abnormal brain excitability.