While the relationship between severe allergies and attention deficit hyperactivity disorder (ADHD) is well described, what links these two pathologies as remained largely unknown. Now, research at the Center for Neuroscience and Cell Biology of the University of Coimbra (CNC-UC) provides new information to understand this link: there is an important period in the postnatal development of the cerebellum during which allergic response disrupts the maturation of this region.
This discovery provides evidence on the mechanisms of neurodevelopment delineating a critical moment in the development of the cerebellum. It also highlights the need for a healthy development of the immune system and how alterations at this level can have an impact on the brain.
In the paper “IL-4 shapes microglia-dependent pruning of the cerebellum during postnatal development”, published in NEURON, João Peça, who led the study says that the main objective were "to study the impact of the allergic response in the cerebellum, which is a region that develops essentially in the postnatal period". He also adds that, "we know there are immune cells in the brain and that they respond to messages and instructions from the periphery, but we know very little about this relationship in critical periods after birth".
In the phase after birth, "under normal conditions, the developing cerebellum needs to ʽgrowʼ, but it also needs to be ʽprunedʽ, whereby excess neurons are eliminated by immune cells called microglia," explains João Peça. "In a severe allergic response, microglia fail to perform this task efficiently, which results in the survival of excess neurons, disrupting the proper functioning of the cerebellum," he adds. In this work using animal models, the research team was also able to observe that when this ʽpruningʼ does not occur, "there are alterations in the functioning of the cerebellum circuits, hyperlocomotion and hyperactivity, characteristics associated with ADHD,".
Regarding future research in this line of investigation, the team from Portugal stresses the importance of "understanding in greater detail why the cerebellum is particularly affected in these processes, as well as the critical window of the ʽpruningʼ, since if the allergic stimulus appears at a later stage of development, neurobehavioral changes no longer manifest."
At the moment, the research group is investigating how the cerebellum regulates the release of dopamine in the context of ADHD, since "understanding this circuit and neurotransmitter could help us better understand this disorder,". ADHD results in learning difficulties and impulsive behavior, mainly affecting children between the ages of 6 and 12, and can have an impact well into adulthood.
The core team members at UC João Peça, Joana Guedes, Ana Luísa Cardoso and Pedro Ferreira were joined by other colleagues, and researchers from Johannes Gutenberg University of Mainz and from the University of Manchester.
The scientific article is available here.
Catarina Ribeiro, João Peça e Sara Varela Amaral