Expression Pattern of ALOXE3 in Mouse Brain Suggests Its Relationship with Seizure Susceptibility
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ORIGINAL RESEARCH
Expression Pattern of ALOXE3 in Mouse Brain Suggests Its Relationship with Seizure Susceptibility Hui‑Ling Tang1,2 · Si‑Yu Chen1,2 · Huan Zhang1,2 · Ping Lu1,2 · Wei‑Wen Sun1,2 · Mei‑Mei Gao1,2 · Xiang‑Da Zeng1,2 · Tao Su1,2 · Yue‑Sheng Long1,2 Received: 29 May 2020 / Accepted: 27 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Arachidonic acid (AA), a polyunsaturated fatty acid, is involved in the modulation of neuronal excitability in the brain. Arachidonate lipoxygenase 3 (ALOXE3), a critical enzyme in the AA metabolic pathway, catalyzes the derivate of AA into hepoxilins. However, the expression pattern of ALOXE3 and its role in the brain has not been described until now. Here we showed that the levels of Aloxe3 mRNA and protein kept increasing since birth and reached the highest level at postnatal day 30 in the mouse hippocampus and temporal cortex. Histomorphological analyses indicated that ALOXE3 was enriched in adult hippocampus, somatosensory cortex and striatum. The distribution was restricted to the neurites of function-specific subregions, such as mossy fibre connecting hilus and CA3 neurons, termini of Schaffer collateral projections, and the layers III and IV of somatosensory cortex. The spatiotemporal expression pattern of ALOXE3 suggests its potential role in the modulation of neural excitability and seizure susceptibility. In fact, decreased expression of ALOXE3 and elevated concentration of AA in the hippocampus was found after status epilepticus (SE) induced by pilocarpine. Local overexpression of ALOXE3 via adeno-associated virus gene transfer restored the elevated AA level induced by SE, alleviated seizure severities by increasing the latencies to myclonic switch, clonic convulsions and tonic hindlimb extensions, and decreased the mortality rate in the pilocarpine-induced SE model. These results suggest that the expression of ALOXE3 is a crucial regulator of AA metabolism in brain, and potentially acts as a regulator of neural excitability, thereby controlling brain development and seizure susceptibility. Keywords Arachidonate lipoxygenase 3 · Spatiotemporal expression · Arachidonic acid · Neural development · Seizure
Introduction
Hui-Ling Tang, Si-Yu Chen have contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10571-020-00974-4) contains supplementary material, which is available to authorized users. * Tao Su [email protected] * Yue‑Sheng Long [email protected] 1
Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, 250 Changang East Road, Guangzhou 510260, China
Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou 510260, China
2
Arachidonic acid (AA), a type of omega-6 fatty acid found in meat and fish, is an essential fatty acid and one of the most abundant polyunsaturated fatty acids (PUFAs) in the
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