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Caffeine intake during lactation has a sex-dependent effect on the hippocampal excitatory/inhibitory balance and
Bruna Teixeira-Silva1, Giovanna Varzea Roberti Monteiro de Mattos1, Vinicius de Frias Carvalho2
1Programa de Pós-graduação em Neurociências, Departamento de Neurobiologia, Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, Brazil.
Insights
Maternal caffeine intake during lactation alters hippocampal synaptic markers and offspring behavior. These sex-dependent effects suggest reduced caffeine consumption for breastfeeding mothers to support healthy neurodevelopment.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Disruptions in hippocampal glutamatergic and GABAergic synapses are linked to neurodevelopmental disorders.
- Caffeine, a widely consumed psychoactive substance, has been shown to affect neural development.
Purpose of the Study:
- To investigate the impact of maternal caffeine consumption during lactation on hippocampal synaptic markers and offspring behavior.
- To determine if these effects are sex-dependent.
Main Methods:
- Lactating rats consumed caffeine, and their offspring were assessed for hippocampal synaptic markers (NMDA receptor subunits, AMPA receptor subunits, GAD) and behavior.
- Behavioral tests included assessments for anxiety-like behavior and hyper-locomotion.
Main Results:
- Maternal caffeine intake altered glutamatergic and GABAergic markers in a sex-specific manner in the hippocampus of offspring.
- Female pups showed reduced NMDA receptor GluN1, increased AMPA receptor GluA1/GluA2 ratio, and decreased GAD in specific hippocampal regions.
- Male pups exhibited increased NMDA receptor GluN1/GluN2b, decreased GAD, and reduced AMPA receptor GluA1 in specific hippocampal regions.
- Offspring behavior was also sex-dependent, with females exhibiting anxiety and males showing anxiety and hyper-locomotion.
Conclusions:
- Maternal caffeine intake during lactation disrupts the excitatory and inhibitory balance in the hippocampus of offspring.
- The observed neurochemical and behavioral changes are sex-dependent.
- Reduced caffeine consumption by breastfeeding mothers is recommended to mitigate potential negative impacts on offspring neurodevelopment.
Abstract:
During early life, disruptions in glutamatergic and GABAergic synapse development in the hippocampus may contribute to several neurodevelopmental disorders, including cognitive deficits and psychiatric disorders. Caffeine is the most consumed psychoactive drug in the world, and previous work from our group has shown that caffeine disrupts visual system connections at different stages of development. This work aimed to investigate the effects of caffeine consumption during lactation in the glutamatergic and GABAergic synaptic markers in the hippocampus and on the behavior of rat offspring. We found that maternal caffeine intake significantly reduced GluN1 subunits of the NMDA receptor, increased the GluA1/GluA2 ratio of AMPA receptor in the dorsal hippocampus, and decreased GAD content in female pups' ventral hippocampus. On the other hand, an increase in GluN1/GluN2b subunits, a decrease in GAD content in the dorsal hippocampus, and a reduction of the GluA1 content in the ventral hippocampus were observed in male pups. In addition, changes in the behavior of the offspring submitted to indirect caffeine consumption were also sex-dependent, with females developing anxiety-like behavior and males showing anxiety-like behavior and hyper-locomotion. These results highlight that maternal caffeine intake promotes changes in the hippocampal excitatory and inhibitory balance and offspring behavior in a sex-dependent manner, suggesting that the population should be alerted to reduced caffeine consumption by breastfeeding mothers.
