Written by Leanna Bai ‘25
Edited by Josephine Chen ‘24
Frontotemporal dementia (FTD) is a neurological disease characterized by the deterioration of cognitive function, like conduct, judgment, and empathy [1]. Representing approximately 10-20% of dementia cases, there is currently no treatment for this disease, and drugs utilized to treat Alzheimer’s disease are ineffective [2]. However, researchers have recently published a unique finding that reveals a new understanding of FTD: the characteristic loss of empathy associated with this disease was discovered to be reversible by boosting brain activity in early mouse models [3].
To determine this result, Phillips et al. demonstrated a homologous form of empathy in their mice test subjects, placing a pair of mice into a cage to interact. The researchers recorded the reactions of one mouse as the other was electrically shocked — overall, the observed mice tended to “freeze up,” characterized by immobility and self-grooming, demonstrating that “emotional contagion” was exhibited and can be depicted in a research setting [3].
Testing the effect of FTD on empathy in mice, the researchers used a virus as a vector to induce the expression of a G-G-G-G-C-C repeated nucleotide pattern in the genome of a strain of mice, emulating the human neurodegeneration phenotype [3]. This experience resulted in a 22-25% neuronal loss within the mice over the course of a year. When these transgenic mice were then assessed for the indicators of empathy used in the control trials — self-grooming, observational fear — they exhibited decreased levels of distress towards the treatment of the mouse receiving electric shocks when compared to the control [3].
Finally, the researchers explored potential mechanisms for the development and inhibition of empathy in the dorsomedial prefrontal cortex (dmPFC), which they determined to be a candidate brain region for controlling prosocial behavior. In experimenting with the region’s excitability, the researchers discovered that increasing neural activity in the dmPFC resulted in a rescue of empathic behavior in the mice. In other words, it is possible to restore empathy in mice exhibiting FTD-like neurodegeneration and symptoms [3].
The findings of this study have fascinating implications and raise interesting questions about human dementia as well as mouse behavior. Firstly, the study demonstrates that neuronal regions can be manipulated to influence behavior even in degenerating brains; extending this idea, drug therapies could be developed by isolating specific cell types in this brain region [4]. As mentioned above, there are currently no FDA-approved treatments for this type of dementia. Furthermore, this paper provides additional insight on rodent cognition, determining that there appears to be some form of empathy exhibited among the mice test subjects. The researchers defend their definition of mouse empathy by reporting that the mice receiving electric shocks alone experienced a significantly lower center-to-total distance ratio, a value inversely proportional to anxiety levels [3,5]. In other words, the mouse receiving shocks was comforted by the presence of the observing mouse’s presence and reactions. Therefore, the study concludes that there is a “social buffering of stress” that occurs among rodents as well.
Overall, this study reveals promising insight about both treatment for frontotemporal dementia in humans and the social frameworks of mice. By determining stimulating areas in degenerating brains to be a potential strategy for combating deteriorating social abilities, the paper opens pathways for the creation of therapeutics for FTD. Additionally, it beckons the reader to question what empathy truly is: can it exist in other animals? Is it no longer a uniquely human experience? And if not, how does it manifest in other species, and, is there really anything that sets us apart?
References
[1] Fast Facts about Frontotemporal Degeneration. Association for Frontotemporal Degeneration [Internet]. 2011 [cited 2023 Mar 6]. Available from: https://www.theaftd.org/wp-content/uploads/2009/02/Fast-Facts-Final-6-11.pdf
[2] Frontotemporal Dementia. Mayo Clinic [Internet]. 2021 Nov 16 [cited 2023 Mar 6]. Available from: https://www.mayoclinic.org/diseases-conditions/frontotemporal-dementia/diagnosis-treatment/drc-20354741
[3] Phillips HL, Dai H, Choi SY, Jansen-West D, Zajicek AS, Daly L, et al. Dorsomedial prefrontal hypoexcitability underlies lost empathy in frontotemporal dementia. Neuron [Internet]. 2023 Jan 12 [cited 2023 Mar 6]. DOI: 10.1016/j.neuron.2022.12.027.
[4] Beans, C. Empathy lost and regained in a mouse model of dementia. PNAS Journal Club [Internet]. 2023 Feb 4 [cited 2023 Mar 6]. Available from: https://www.pnas.org/post/journal-club/empathy-lost-and-regained-mouse-model-dementia
[5] Saré R, Figueroa C, Lemons A, Loutaev I, Beebe Smith C. Comparative Behavioral Phenotypes of Fmr1 KO, Fxr2 Het, and Fmr1 KO/Fxr2 Het Mice. Brain Sciences [Internet]. 2019 Jan 16 [cited 2023 Mar 6]. DOI: 10.3390/brainsci9010013.
[Image] White-lab-mouse-with-cute-little-snout-pointed-at-us.jpg [Internet] [cited 2023 Mar 6] Available from: https://twin-cities.umn.edu/news-events/dirty-mice-model-human-biology-better
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