Researchers from the NEUROFAN group at the School of Pharmacy, dedicated to neuropharmacology of addictions and degenerative disorders and led by Professor Gonzalo Herradón, have described, for the first time, a fundamental alteration that alcohol generates in the teenage brain, in collaboration with researchers from the Miguel Hernández University.

"We have observed that intermittent alcohol consumption during adolescence produces a marked decrease in perineuronal networks in the hippocampus, a fundamental brain area in memory and learning processes. These networks constitute the matrix that surrounds neurons and protects them from various damages, such as exposure to a toxin like alcohol," explains Professor Herradón. In this sense, he specifies: "We have demonstrated that pharmacological modulation of a key protein for the anchoring of these perineuronal networks regulates these alcohol effects and prevents the damage caused by this drug to the hippocampal neuronal progenitors."

The work has been published in the journal Neuropharmacology and gathers the evidence that led researchers to demonstrate, in an animal model reflecting intermittent alcohol consumption during adolescence, the so-called "botellón", that this alcohol consumption significantly reduces perineuronal networks in the hippocampus. "Without the matrix that surrounds the neurons, they may be more vulnerable to the neurotoxic effects of alcohol. This could be the cause of the large loss of immature neurons in the teenage hippocampus after consuming large amounts of alcohol, which has been associated with short and long-term cognitive problems, and an increased risk of early-onset dementia or other neurodegenerative diseases," says Herradón.

The NEUROFAN group belongs to the Research Network on Addiction Primary Care (RIAPAd), and this finding has resulted from a research project funded by the National Drugs Plan granted in 2019. With this project, it was observed how the pharmacological modulation of the PTPRZ protein, which plays a key role in the matrix surrounding neurons, can prevent the effects of alcohol on the teenage hippocampus.

"Our studies demonstrate in animal models reflecting alcohol consumption observed in teenagers during a 'botellón', that the pharmacological regulation of this protein prevents the effects of alcohol on perineuronal networks and protects the developing neurons of the teenage hippocampus, which is important because these neuronal progenitors are necessary later in life to become mature neurons and alleviate the effects of aging on the brain," says Gonzalo Herradón.

Precisely, with the new project funded by the National Drugs Plan granted in the 2023 call to Professor Herradón's group, it is intended to study whether the beneficial effects of this new therapeutic strategy are also capable of preventing long-term cognitive impairment observed after episodic consumption of high amounts of alcohol during adolescence.

The NEUROFAN group has been studying how the PTPRZ receptor functions in the brain for years. In this regard, in recent years, a significant milestone for the group has been the development of new compounds regulating the activity of PTPRZ thanks to collaboration with the research groups PROLIGAR and GESTOBES from Universidad CEU San Pablo. The lead compound, MY10, has demonstrated its effectiveness in blocking the neurotoxic effects of alcohol on the teenage brain. "These results mark the beginning of the discovery of new drugs active in the treatment of alcohol use disorder and in the prevention of brain damage caused by this substance, including long-term cognitive impairment and the development of premature dementia," details Professor Herradón.

More information:

Galán-Llario M, Gramage E, García-Guerra A, Torregrosa AB, Gasparyan A, Navarro D, Navarrete F, García-Gutiérrez MS, Manzanares J, Herradón G. “Adolescent intermittent ethanol exposure decreases perineuronal nets in the hippocampus in a sex dependent manner: Modulation through pharmacological inhibition of RPTPß/?”. Neuropharmacology, 247:109850, 2024.

https://doi.org/10.1016/j.neuropharm.2024.109850