Melatonin Improves Memory Deficits in Rats with Cerebral Hypoperfusion, Possibly, Through Decreasing the Expression of Small-Conductance Ca2+-Activated K+ Channels

Hussain Al Dera*, Mohammed Alassiri, Samy M. Eleawa, Mahmoud A. AlKhateeb, Abdelaziz M. Hussein, Mohammad Dallak, Hussein F. Sakr, Sultan Alqahtani, Mohammad A. Khalil

*المؤلف المقابل لهذا العمل

نتاج البحث: المساهمة في مجلةمراجعة النظراء

11 اقتباسات (Scopus)

ملخص

This study investigated the expression pattern, regulation of expression, and the role of hippocampal small-conductance Ca2+-activated K+ (SK) channels in memory deficits after cerebral hypoperfusion (CHP) with or without melatonin treatment, in rats. Adults male Wistar rats (n = 20/group) were divided into (1) a sham (2) a sham + melatonin (3) a two-vessel occlusion (2-VO) model, and (4) a 2-VO + melatonin. Melatonin was administered (i.p.) to all rats at a daily dose of 10 mg kg−1 for 7 days starting at the time of 2-VO-induction. In contrast to 2-VO rats, melatonin increased the latency of the passive avoidance learning test and decreased time to find the hidden platform in Water Morris Test in all tested rats. In addition, it concomitantly downregulated SK1, SK2, and SK3 channels, downregulated mRNA levels of TNFα and IL-1β, enhanced BDNF levels and activity of PKA levels, and restored the levels of cholinergic markers in the hippocampi of the treated-rats. Mechanistically, melatonin significantly prevented CHP-induced activation of ERK1/2, JNK, and P38 MAPK at least by inhibiting ROS generation and enhancing the total antioxidant potential. In cultured hypoxic hippocampal neurons, individual blockage of MAPK signaling by the MEK1/2 inhibitor (U0126), but not by the P38 inhibitor (SB203580) or JNK inhibitor (SP600125), completely prevented the upregulation of all three kinds of SK channels. These data clearly confirm that upregulation of SK channels plays a role in CHP-induced memory loss and indicate that melatonin reverses memory deficits after CHP in rats, at least by, downregulation of SK1, SK2, and SK3 channels in their hippocampi.

اللغة الأصليةEnglish
الصفحات (من إلى)1851-1868
عدد الصفحات18
دوريةNeurochemical Research
مستوى الصوت44
رقم الإصدار8
المعرِّفات الرقمية للأشياء
حالة النشرPublished - أغسطس 1 2019

ASJC Scopus subject areas

  • ???subjectarea.asjc.1300.1303???
  • ???subjectarea.asjc.2800.2804???

بصمة

أدرس بدقة موضوعات البحث “Melatonin Improves Memory Deficits in Rats with Cerebral Hypoperfusion, Possibly, Through Decreasing the Expression of Small-Conductance Ca2+-Activated K+ Channels'. فهما يشكلان معًا بصمة فريدة.

قم بذكر هذا