Details

Autor(en) / Beteiligte

• Aratake, Takaaki
• Higashi, Youichirou
• Hamada, Tomoya
• Ueba, Yusuke
• Shimizu, Takahiro
• Shimizu, Shogo
• Yawata, Toshio
• Ueba, Tetsuya
• Saito, Motoaki

Titel

The role of diurnal fluctuations in excitatory amino acid carrier 1 levels in post-ischemic hippocampal Zn2+ accumulation

Ist Teil von

• Experimental neurology, 2021-02, Vol.336, p.113538-113538, Article 113538

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2021

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Accumulating evidence indicates time-of-day variations in ischemic neuronal injury. Under ischemic conditions, Zn2+ is massively released from hippocampal glutamatergic neurons, and intracellular Zn2+ accumulation results in neuron death. Notably, excitatory amino acid carrier 1 (EAAC1), known as a cysteine transporter, is involved in Zn2+ homeostasis, and its expressions exhibit a diurnal fluctuation. This study aimed to investigate whether time of day of an ischemic insult affects Zn2+ accumulation and neuronal injury and determine whether altered Zn2+ accumulation is modulated by EAAC1 diurnal fluctuation in the hippocampus in a mouse model of ischemic stroke. Mice subjected to transient global ischemia for 40 min at Zeitgeber time 18 (ZT18) (23:00) exhibited reduced Zn2+ accumulation and neuronal death in the hilar region of the hippocampus compared to those at ZT4 (09:00). The EAAC1 protein expression in the hippocampus was increased at ZT18 relative to ZT4. Intracerebroventricular injection of a non-selective excitatory amino acid transporter inhibitor, DL-threo-β-benzyloxyaspartate, or a selective EAAC1 inhibitor, L-aspartic acid β-hydroxamate, increased ischemia-induced Zn2+ accumulation and neuronal death in the hilus at ZT18. These findings suggest that ischemia-induced Zn2+ accumulation displays circadian fluctuations through diurnal variations in EAAC1 expressions and affects susceptibility to ischemic neuronal injury in the hippocampal hilar region. •Ischemia-induced Zn2+ accumulation in the hilus exhibited diurnal variations.•Hippocampal EAAC1 protein expression increased in the dark period.•EAAC1 inhibition increased ischemia-induced hilar Zn2+ accumulation and neuron death.