The effect of magnesium l-threonate on cognitive functions in A rat model of Aß 1-42 peptide induced alzheimer's disease

Introduction and Aim Alzheimer's disease constitutes the majority of demensia cases. Although there is no complete cure ,it is aimed to slow down the prognosis of the disease with some treatment modalities.There are many mechanisms in its physiopathology with these mechanisms also there are studies support that some nutritional elements play a key role in Alzheimer's disease.Among the minerals , magnesium is the most prominent potential risk factor for Alzheimer's. Magnesium deficiency is associated with Alzheimer's and many neurodegenerative diseases. The aim of this study is to compare the effects of magnesium L-threonate, a magnesium compound, and memantine, an NMDA antagonist used in the treatment of Alzheimer's disease, when administered separately or together on cognitive functions in a rat model of Aß 1-42 peptide induced Alzheimer's. Method Fourty two adult male Sprague Dawley rats were used in this study. In the study, after 14 days of habituation period the rats were randomly divided into six groups as control, sham ,Alzheimer, Alzheimer+ Memantine ,Alzheimer + Magnesium L-threonate and Alzheimer +Memantine +Magnesium L-threonate. Aβ1-42 peptide was administered by intracerebroventricular injection to rats to be modeled Alzheimer's disease, and drug administration was started for the groups that would receive memantine and magnesium L-threonate 2 weeks after the procedure. On the 45th day of the experiment, behavioral tests were administered to the rats to assess learning, memory and anxiety levels. Afterwards, the subjects were sacrificed and BDNF, MDA, T-AOC, TNF-α levels were measured in the hippocampus and prefrontal cortex. Findings On the 5th day of the MWM test, it was observed that the time spent in the platform area of the Alzheimer group decreased compared to the control group (p<0.01). It was observed that MDA and TNF-α levels in the hippocampus and prefrontal cortex tissues increased in the Alzheimer group compared to the control group, while TAOC and BDNF levels decreased. In the Alz + Memantine and ALZ + Mg L-threonate groups, hippocampus BDNF levels were found to be increased compared to the Alzheimer group (p<0.05). In the Alz + Memantine + Mg L-threonate group, hippocampus BDNF levels increased and reached the BDNF levels of control group ( p<0,0001). Hippocampal MDA levels of ALZ + Memantine , ALZ + Mg L-threonate and ALZ + Memantine + Mg L-threonate groups were decreased compared to Alzheimer group ( p<0.05). Hippocampus and prefrontal cortex T-AOC levels were higher in the Alz+ Mem + Mg L-threonate group compared to the Alzheimer group (p<0.05). It was observed that the hippocampus and prefrontal cortex TNF-α levels of ALZ + Memantine , ALZ + Mg L-threonate and ALZ + Memantine + Mg L-threonate groups were significantly decreased compared to the Alzheimer group. Results In this study, it was observed that the administration of Memantine and Mg L-threonate together in the rats that Aß 1-42 peptide induced AD model ,had a more positive effect on cognitive functions than administration separately. In addition, it was observed that the oxidative stress induced by the application of Aß 1-42 peptide regressed with the co-administration of Memantine and Mg L-threonate. Studies in which Memantine and Mg L-threonate were applied separately in AD rat models were found in the literature and in this study the evaluation of the combined effect of both ,constitutes the original value of the study. In this sense, the application of Mg L-threonate together with Memantine treatment in Alzheimer's patients will increase the effectiveness of the treatment. It is thought that our study results can shed light on new experimental research and studies in this field. Keywords: Alzheimer ,Mg L-threonate, Memantine, Aß 1-42 peptide, rat