engleski

Plasma membrane Ca2+ ATPase expression and activity in Toll-like receptor 2 deficient mice

Toll-like receptor 2 (TLR2) deficient mice model is widely used for investigation of microglial role in regulating inflammatory response following ischemic brain lesion (1). Additional functions and broader cell-type expression of TLRs have been evidenced in brain tissue which makes TLRs knock- out mice (such as TLR2-KO) a promising model for investigating neuron-microglia interactions, and microglial regulation of plasticity and excitability (2). Plasma membrane Ca2+ ATPases (PMCAs) participate significantly in ion homeostasis maintenance and signal transduction in brain tissue, thus we aimed to examine PMCAs protein expression and catalytic activity across brain regions in TLR2-KO mice. Results acquired by Western blot analysis and spectrophotometric enzyme activity measurements exhibit strikingly different protein expression and enzyme activity in brain tissue samples derived from TLR2-KO when compared with wild-type (WT) mice. Observed abundance of PMCA expression across cortex, hippocampus and cerebellum suggests that ubiquitous isoforms, PMCA 1 and 4 are less affected by TLR2 deficiency than neuron specific isoforms, PMCA 2 and 3. Notably, higher expression of PMCA2 in hippocampus and lower in cerebellum of TLR2-KO coincide with catalytic PMCA activity variations, higher activity is detected in hippocampus and lower in cerebellum of TLR2-KO compared with WT controls. Here collected evidence suggests that TLR2 deficiency is accompanied by a disturbance of neuronal Ca2+ signaling system. Further investigation should clarify in more details a potential impact of TLR2 on establishing proper neuron-microglia interactions and regulation of neurotransmission. [1.] Gorup D, Škokić S, Kriz J, Gajović S. Tlr2 Deficiency is Associated with Enhanced Elements of Neuronal Repair and Caspase 3 Activation Following Brain Ischemia. Sci Rep. 2019 ; 9(1):1–10. [2.] Yamamoto M, Kim M, Imai H, Itakura Y, Ohtsuki G. Microglia- Triggered Plasticity of Intrinsic Excitability Modulates Psychomotor Behaviors in Acute Cerebellar Inflammation. Cell Rep [Internet]. 2019 ; 28(11):2923-2938.e8. Available from: https://doi.org/10.1016/j.celrep.2019.07.078 [3.] Hajieva P, Baeken MW, Moosmann B. The role of Plasma Membrane Calcium ATPases (PMCAs) in neurodegenerative disorders. Neurosci Lett. 2018 ; 663(September 8. Available from: https://doi.org/10.1016/j.neulet.2017.09.033 Funding: Croatian Science Foundation (IP-2016-06- 8638), European Social Fund (ESF), and Centre of Excellence for basic, clinical and translational neuroscience.

PMCA ; TLR2

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