Effects of thymoquinone and memantine alone and in combination on memory and hippocampal morphology in rats with streptozotocin-induced Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease. Thymoquinone (TQ) has broad biological functions, including antiinflammatory, antioxidant, neuroprotective properties. Memantine (MEM) is indicated for the symptomatic treatment of moderate to severe AD. We aimed to evaluate the effect of TQ alone or in combination with MEM on memory and hippocampal morphology in an STZ-induced rat AD model. METHODS: Thirty male rats were included in this study. The AD model was created by giving ICV STZ. The rats were divided into 5 groups (n = 6 each). Group 1 (control group): The rats received only ICV-STZ 3 mg/kg for 2 weeks. Group 2 (sham group): In addition to ICV STZ, 9% NaCl, 1 mL/day i.p. for 2 weeks of injection, was applied. Group 3 (TQ group): In addition to ICV STZ, rats received TQ 10 mg/kg i.p. for 2 weeks. Group 4 (MEM group): In addition to ICV STZ, rats were given MEM at a dose of 5 mg/kg for two weeks. Group 5 (TQ+MEM group): In addition to ICV STZ, this group was given TQ (10 mg/kg/day, i.p.) and MEM (5 mg/kg/day, i.p.) for 2 weeks. On the 15th day, passive avoidance learning (PAL) was applied to all groups. Then, rats were sacrificed, neurons in the hippocampal CA1, CA2, CA3 regions were evaluated. RESULTS: Groups 3, 4, 5 had longer latency periods than groups 1 and 2. The neuron density in the CA1, CA2, CA3 regions had decreased in groups 1 and 2 compared to groups 3, 4, 5. There were significantly more neurons in groups 3, 4, 5 than in groups 1 and 2. DISCUSSION: We found that TQ alone and in combination with MEM showed ameliorative effects on memory and hippocampal morphology. TQ may offer a promising treatment strategy for AD.

Acid-sensing ion channels (ASICs) influence excitability of stellate neurons in the mouse cochlear nucleus.

Acid-sensing ion channels (ASICs) are voltage-independent and proton-gated channels. In this study, we aimed to test the hypothesis whether ASICs might be involved in modifying the excitability of stellate cells in the cochlear nucleus (CN). We determined gene expressions of ASIC1, ASIC2 and ASIC3 in the CN of BALB/mice. ASIC currents in stellate cells were characterized by using whole-cell patch-clamp technique. In the voltage-clamp experiments, inward currents were recorded upon application of 2-[N-Morpholino ethanesulfonic acid]-normal artificial cerebrospinal fluid (MES-aCSF), whose pH 50 was 5.84. Amiloride inhibited the acid-induced currents in a dose-dependent manner. Inhibition of the ASIC currents by extracellular Ca2+ and Pb2+ (10 µM) was significant evidence for the existence of homomeric ASIC1a subunits. ASIC currents were increased by 20% upon extracellular application of Zn2+ (300 µM) (p < 0.05, n = 13). In current-clamp experiments, application of MES-aCSF resulted in the depolarization of stellate cells. The results show that the ASIC currents in stellate cells of the cochlear nucleus are carried largely by the ASIC1a and ASIC2a channels. ASIC channels affect the excitability of the stellate cells and therefore they appear to have a role in the processing of auditory information.