A01 A02 A03 A04 A05 A06 A07 A09 A10 A11 A12 A13 A14 A18 A19 A21 F01 F02 INF Ö

A18 – How learning shapes immunity

Martin Hadamitzky, Manfred Schedlowski

Based on our established taste-immune paradigm in rats employing the immunosuppressive drug cyclosporine A (CsA), we will investigate extinction and reconsolidation of behavioral conditioned immune responses of immunomodulating compounds with distinct cell signaling pathways (rapamycin, methotrexate), Moreover, we will employ DREADDs to analyze the role of brain structures steering these learning processes, and will analyze the potential clinical relevance of learned immunomodulation employing a tumor model as well as a model of chronic inflammatory autoimmune disease.

Guiding questions of A18:

  • Are learned immune responses restricted to calcineurin inhibitors such as CsA or does conditioning with other immunomodulating drugs and distinct cell signaling pathways such as RAPA or MTX operate under similar mechanisms?
  • Which brain areas mediate learning and extinction processes of conditioned immunopharmacological effects?
  • Can extinction of the learned immunopharmacological effects of RAPA and MTX be inhibited by administering sub- or low-therapeutic drug doses during retrieval as reminder cues concomitantly with the CS?
  • Are behaviorally conditioned anti-proliferative (RAPA) and anti-metabolic effects (MTX) of clinical relevance by interfering with disease progression in animal models of tumor growth and inflammatory autoimmune diseases?
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Martin Hadamitzky

Project Lead A18

University of Duisburg-Essen

Julia Bihorac

PhD Student A18

University of Duisburg-Essen

10 project-relevant publications

Bihorac J, Salem Y, Lückemann L, Schedlowski M, Doenlen R, Engler H, Mark MD, Dombrowski K, Spoida K, Hadamitzky M (2024) Investigations on the Ability of the Insular Cortex to Process Peripheral Immunosuppression. J Neuroimmune Pharmacol 19:40. https://doi.org/10.1007/s11481-024-10143-9 

Hadamitzky M, Bosche K, Wirth T, Buck B, Beetz O, Christians U, Schniedewind B, Luckemann L, Güntürkün O, Engler H, Schedlowski M (2016) Memory-updating abrogates extinction of learned immunosuppression. Brain Behav Immun 52:40-48. https://doi.org/10.1016/j.bbi.2015.09.009

Hadamitzky M, Lückemann L, Pacheco-López G, Schedlowski M (2020) Pavlovian Conditioning of Immunological and Neuroendocrine Functions. Physiol Rev. 100:357-405. https://doi.org/10.1152/physrev.00033.2018 

Hadamitzky M, Schedlowski M (2022) Harnessing associative learning paradigms to optimize drug treatment. Trends Pharmacol Sci. 43:464-472. https://doi.org/10.1016/j.tips.2022.03.002 

Hetze S, Barthel L, Lückemann L, Günther HS, Wülfing C, Salem Y, Jakobs M, Hörbelt T, Bendix I, Sure U, Petschulat J, Schedlowski M, Hadamitzky M (2022). Taste-immune associative learning amplifies immunopharmacological effects and attenuates disease progression in a rat glioblastoma model. Brain Behav Immun. 106:270-279. https://doi.org/10.1016/j.bbi.2022.09.006 

Jakobs M, Hörbelt-Grünheidt T, Hadamitzky M, Julia Bihorac, Salem Y, Leisengang S, Christians U, Schniedewind B, Schedlowksi M, Hadamitzky M, Lückemann L (2024b). The effects of fingolimod (FTY720) on leukocyte subset circulation cannot be behaviorally conditioned in rats. J Neuroimmune Pharm. 19:18. https://doi.org/10.1007/s11481-024-10122-0 

Lückemann L, Hetze S, Hörbelt T, Schedlowski M, Hadamitzky M (2021) Incomplete reminder cues trigger memory reconsolidation and sustain learned immune responses. Brain Behav Immun. 95:115-121. https://doi.org/10.1016/j.bbi.2021.03.001 

Lückemann L, Stangl H, Straub RH, Schedlowski M, Hadamitzky M (2020) Learned immunosuppressive placebo response attenuates disease progression in a rodent model of rheumatoid arthritis. Arthritis Rheumatol. 72:588-597. https://doi.org/10.1002/art.41101 

Lückemann L, Unteroberdörster M, Martínez-Gómez EM, Schedlowski M, Hadamitzky M (2019) Behavioral Conditioning of Anti-Proliferative and Immunosuppressive Properties of the mTOR Inhibitor Rapamycin. Brain Behav Immun. 79:326-331. https://doi.org/10.1016/j.bbi.2019.04.013

Schwarting RKW, Wöhr M, Engler H, Sungur A, Schedlowski M (2024) Behaviorally conditioned effects of psychoactive drugs in experimental animals: What we have learned from nearly a century of research and what remains to be learned. Neurosci Biobehav Rev 162:105721. https://doi.org/10.1016/j.neubiorev.2024.105721

New Year, New Me: The Facts

As the calendar turns to a new year, millions of people around the world commit to New Year’s resolutions, making promises to use the new year as a fresh beginning and an opportunity for transformation. In 2024, almost three-quarters of the British population set themselves New Year’s resolutions — that’s around 40 million people (or the entire population of Canada). This tradition was particularly strong among younger generations, with 96% of Generation Z (aged 18-27) planning resolutions, compared to just 35% of the Silent Generation (aged 79+).

Most common new years resolutions:

  1. Saving more money (52%)
  2. Eat healthier (50%)
  3. Exercise more (48%)
  4. Lose weight (37%)
  5. Spend more time with family/friends (35%)

How long do most resolutions normally last before being broken?

  • Data from America (2016) shows that 75% of individuals maintain their resolutions through the first week. 
  • 64% of individuals maintain their resolutions through the first month. 
  • 46% of individuals in America keep their resolutions past the 6-month mark.

What makes resolutions stick?

Oscarsson et al. (2020) conducted research into what makes New Year’s resolutions stick. Biggest success rates depended on how people phrased their goals. Participants who set approach-oriented goals (trying to move toward or maintain a desirable outcome or state) than those with avoidance-oriented goals (trying to move toward or maintain a desirable outcome or state) were significantly more successful (58.9% vs. 47.1%) at sticking to their goals.

The study also investigates the effects of outside support. These participants received monthly follow-ups and emails with information and exercises for coping with hurdles when striving toward personal goals, and were also encouraged to set goals using the SMART technique and to set interim goals. The group that received some support was exclusively and significantly more successful compared to the groups who received a lot of support or no support at all. 

Additionally, you might feel more successful if you set goals that are measurable in numbers. While success for a person striving to quit smoking or lose weight could easily be measured in the number of cigarettes smoked or body mass index, the success for a person striving to “take better care of themselves” could be highly subjective and possibly impossible to measure.

So as we enter 2026, let’s remember to work with our brain’s natural learning system: Frame your goals positively, break them into manageable steps, and celebrate small wins along the way.