Functional Significance of TREM2 Knockout on Microglia Response and Seizure Development After Intra-Amygdala Kainic Acid
Abstract number :
3.068
Submission category :
1. Basic Mechanisms / 1F. Other
Year :
2021
Submission ID :
1825556
Source :
www.aesnet.org
Presentation date :
12/6/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:44 AM
Authors :
Dale Bosco, PhD - Mayo Clinic; Manling Xie, BS - Mayo Clinic; Jiaying Zheng, MS - Mayo Clinic; Long-Jun Wu, PhD - Mayo Clinic
Rationale: While it has been classically understood that microglia serve as the primary immune cells of the central nervous system (CNS), they have recently been shown to perform a diverse set of physiological functions, such as sculpting circuit formation and maintenance of synaptic plasticity. They also play critical roles within pathological conditions, such as stroke, pain, and neurodegeneration. However, comparatively little is known about how microglia affect epilepsy pathology. Triggering receptor expressed on myeloid cells 2 (TREM2) is an surface receptor that, within the CNS, is exclusively expressed by microglia and is a suggested regulator of their function. While the function of TREM2 has been explored within other conditions, such as Alzheimer’s disease, little is known about how this receptor affects epileptogenesis, even though TREM2 dysfunction may affect seizure development within Nasu-Hakola disease patients.
Methods: For our investigations we determined the effect that general knock-out (KO) of TREM2 had upon microglial activation and seizure development using the intra-amygdala kainic acid (IA-KA) model. These effects were explored using video-EEG analysis, immunofluorescentchemistry, and in vitro analysis.
Results: We found that TREM2 KO reduced both microglial proliferation and morphological changes following IA-KA administration. Moreover, in vivo and in vitro results indicate that the phagocytic ability of microglia is also attenuated by TREM2 KO. Finally, we found that TREM2 KO mice had a higher incidence and frequency of spontaneous recurrent seizures (SRS) following the initial IA-KA insult.
Conclusions: Our results indicate that TREM2 is a potent mediator of microglial function and by extension seizure development within the IA-KA model. These results offer insight into how microglia may regulate epileptogenesis and provide novel therapeutic targets.
Funding: Please list any funding that was received in support of this abstract.: This work is supported by the NIH National Institute of Neurological Disorders and Stroke (R01NS088627).
Basic Mechanisms