2023-09-28 18:45:51
Fetal Alcohol Spectrum Disorder (FASD) includes a series of conditions suffered by children who have been exposed to alcohol during pregnancy. The effects of FASD vary from craniofacial morphological malformations or growth problems, in the most severe cases, to hyperactivity, emotional and motivational difficulties or defects in learning and memory, in the mildest cases.
Researchers from the Department of Medicine and Life Sciences (MELIS) of the Pompeu Fabra University (UPF) in Barcelona, with the participation of the HMRI (Hospital del Mar Research Institute), have identified and validated, for the first time, in mice, the neurobiological mechanism and therapy to correct the memory deficit of individuals with fetal alcohol spectrum disorder. These results open the door to studying whether the mechanism is the same in humans, which would improve the diagnosis and treatment of affected individuals.
“In children who look normal, FASD is underdiagnosed and is often confused with hyperactivity or ADD,” explains Rafael de la Torre, coordinator of the Integrated Pharmacology and Systems Neuroscience Research Group at the Hospital del Mar Research Institute. . “As there is no diagnosis, there is no treatment and we end up doing symptomatic therapy to relieve hyperactivity or other disorders such as anxiety.”
The results of the new study have allowed researchers to observe that “chronic exposure to alcohol is not necessary for FASD to occur. Sporadic consumption with intoxication (what we commonly know as drunkenness) is enough to observe alterations in memory in mice,” explains Olga Valverde, coordinator of the study and director of the Behavioral Neurobiology Research Group at MELIS.
The study found that mice born to mothers who had sporadic alcohol consumption during pregnancy and lactation have a memory deficit that persists into adulthood. One of the reasons for this deficit is that alcohol affects the function of the endocannabinoid system, reducing the expression of the PPAR-gamma receptor.
“The endocannabinoid system is closely involved in learning and memory processes,” explains De la Torre. “That is why it is especially relevant that this decrease occurs during childhood, when mice, both male and female, are of learning age.” However, the reduction in PPAR-gamma does not occur throughout the brain. It is limited to astrocytes (cells that support neurons by controlling functions such as their metabolism or the inflammation to which they are subjected) of the hippocampus.
After confirming the neurobiological mechanism through three different routes, the study also proposes an effective treatment with the drug pioglitazone, commonly used to control sugar and which stimulates PPAR receptors. According to the first author of the study, Alba Garcia-Baos, “it manages to alleviate the cognitive memory deficits of individuals with FASD in childhood.”
From left to right: Inés Gallego, Antoni Pastor, Alba Garcia-Baos, Olga Valverde and Rafael de la Torre. (Photo: UPF)
Optimism regarding human studies
The results of this study open the door to studying the effects of other cognitive alterations caused by alcohol exposure during pregnancy. “In this work we have only studied alterations in memory, but there may be emotional, motivational or behavioral alterations related to FASD,” points out Valverde, who is also a professor in Psychobiology at the UPF.
Although this study was carried out in mice, the researcher is optimistic about verifying whether this mechanism is replicated in humans “because we are two species of mammals with many similarities.” Furthermore, if confirmed, “it would be relatively simple to carry out a study to validate whether the therapy we propose works in humans, since there are drugs that have similar effects to those we have used that are approved for use in the pediatric population.”
The study is titled “The role of PPAR-γ in memory deficits induced by prenatal and lactation alcohol exposure in mice.” And it has been published in the academic journal Molecular Psychiatry. (Source: UPF)
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