Seasonal allergies pollinating the brain

March 26th, 2024

Written by: Andrew Nguyen

Spring is the season of rejoice, rebirth, and rejuvenation! Picture this: you are taking a stroll next to the river trail, the cherry blossoms are emerging from their buds bringing a pop of color back to the skies and the warmth of the sun is like a big hug on your skin… then all of a sudden that the feeling of an itchy nose shows up and the next thing you know- AH CHOO!! Seasonal allergies can hit hard with symptoms like sneezes, coughs, itchy throats, lack of smell, and fatigue. Many allergy symptoms arise because these allergies influence the brain in fascinating ways. 

What are seasonal allergies and how do they work?

Our bodies are usually very good at distinguishing between safe and harmful substances, choosing the right way to respond to exposure to our environment. Allergies can be thought of as inappropriate immune responses to typically safe substances, like plant pollen, pet dander, dust mite particles to name a few. These usually harmless substances are called allergens. Allergens commonly interact with places in our body that get exposed to the outside environment like our skin, airway systems, and in our GI tract, which explains why allergic reactions are commonly from skin contact with irritants that give us rashes, pollen and dust inhalation that can trigger seasonal allergies and asthma, and dietary ingestion that can trigger food allergies. Springtime seasonal allergies, often referred to as “hay fever”, act through plant pollen in the air entering the nasal airway and triggering an allergic reaction^1-3. 

Our immune systems mount responses to allergens using a few different tactics. One important method is through the production and use of molecules called antibodies that recognize invading allergens and sound the alarm for immune cells. Specific antibodies called immunoglobulin E (IgE) antibodies increase their production in immune cells from the first exposure to allergens, preparing our immune systems to respond with allergic reactions at the next exposure. When we are re-exposed to the same allergens, the IgE antibodies that were produced the first time around are activated and trigger the release of chemicals in immune cells called histamines. Histamines go on to initiate immune responses that lead to many allergy symptoms, like the sneezing and itchy eyes that we commonly experience during springtime². 

Histamines can support a large number of functions in the body. For example, they activate brain cells during hay fever that help coordinate the motor responses that elicit sneezing and coughing. Scientists have recently been able to identify connections in the brain that go from cells in the nose to the brainstem that trigger a sneezing reflex in mice⁴. The team sprayed histamines and other sneezing agents into the nose of mice and were able to use a combination of different neuroscience techniques to trace out the connections of this circuit, including the signals that help relay the information between these brain cells⁴. 

Many people take antihistamines like Benadryl and Claritin to alleviate their allergy symptoms in the spring. Many common over-the-counter antihistamines work by binding to specific histamine docking sites to block histamines from working. If histamines are blocked from their docking sites, they cannot go on to produce the many allergy symptoms we are familiar with. This is how many popular commercial antihistamines like Benadryl and Claritin work to relieve allergy symptoms. Oftentimes, allergies and allergy relief medicine like Benadryl can cause drowsiness and fatigue, suggesting there is a relationship between allergy-related histamines and sleep⁵. One study compared groups of people who have extreme seasonal allergies to otherwise healthy groups and found that during springtime seasonal allergy season, individuals with more severe allergies had more disrupted sleep and fatigue compared to the less allergic group⁶. 

Spring Rebirth and Seasonal Allergies

During the season of rebirth, it is fitting that our brains respond to allergies with its own rebirth. Scientists studying the brain’s response to allergic reactions from plant pollen noticed an interesting pattern of many new neurons being born in a brain region called the hippocampus which is important for learning and memory, a process called neurogenesis. The authors also reported surprising decreases of activity and abundance of brain immune cells, or microglia, in the brain of mice who had allergic reactions. 

This finding highlights a beautiful parallel of rebirth in nature and the brain, opening up many questions to understand how our brains respond to seasonal allergies. What does this mean for learning and memory of people who experience extreme seasonal allergies? Neurogenesis often decreases as we get older, so how does this process look in older individuals who have experienced a lifetime of severe seasonal allergies? What are the consequences of having decreased immune cell activity in the brain from seasonal allergies? Studying how the brain responds to inappropriate immune responses can help us develop better allergy relief medicines, understand the complex relationship between the immune and nervous system, and give us a better understanding of how our brains react to seasonal changes.

References

1. https://www.mountsinai.org/health-library/diseases-conditions/allergic-rhinitis
2. Voisin T, Bouvier A, Chiu IM. Neuro-immune interactions in allergic diseases: novel targets for therapeutics. Int Immunol. 2017 Jun 1;29(6):247-261. doi: 10.1093/intimm/dxx040. PMID: 28814067; PMCID: PMC5890890.
3. Bradley J. Undem, Radhika Kajekar, Dawn D. Hunter, Allen C. Myers, Neural integration and allergic disease, Journal of Allergy and Clinical Immunology, Volume 106, Issue 5, Supplement, 2000, Pages S213-S220,
4. Li, F. et al. Sneezing reflex is mediated by a peptidergic pathway from nose to brainstem. Cell 184, 3762–3773.e10 (2021).
5. Shan L, Dauvilliers Y, Siegel JM. Interactions of the histamine and hypocretin systems in CNS disorders. Nat Rev Neurol. 2015 Jul;11(7):401-13. doi: 10.1038/nrneurol.2015.99. Epub 2015 Jun 23. PMID: 26100750; PMCID: PMC8744538.
6. Sandra Tamm, Simon Cervenka, Anton Forsberg, Johanna Estelius, Johan Grunewald, Pär Gyllfors, Bianka Karshikoff, Eva Kosek, Jon Lampa, Catarina Lensmar, Victoria Strand, Torbjörn Åkerstedt, Christer Halldin, Martin Ingvar, Caroline Olgart Höglund, Mats Lekander, Evidence of fatigue, disordered sleep and peripheral inflammation, but not increased brain TSPO expression, in seasonal allergy: A [11C]PBR28 PET study, Brain, Behavior, and Immunity, Volume 68, 2018, Pages 146-157, ISSN 0889-1591, https://doi.org/10.1016/j.bbi.2017.10.013.
7. Klein Barbara, Mrowetz Heike, Thalhamer Josef, Scheiblhofer Sandra, Weiss Richard, Aigner Ludwig, Allergy Enhances Neurogenesis and Modulates Microglial Activation in the Hippocampus, Frontiers in Cellular Neuroscience, 10, 2016, 10.3389/fncel.2016.00169, 1662-5102 

Cover Photo by Diana Polekhina on Unsplash