Physiology and Pharmacology

en Minocycline did not prevent the neurotoxic effects of amyloid β on intrinsic electrophysiological properties of hippocampal CA1 pyramidal neurons in a rat model of Alzheimer’s disease Neurophysiology/Pharmacology Neurophysiology/Pharmacology Experimental research article Experimental research article Introduction: Although aging is the most important risk factor for Alzheimer's disease (AD), there is evidence indicating that neuroinflammation may contribute to the development and progression of the disease. Several studies indicated that minocycline may exert neuroprotective effects in rodent models of neurodegenerative diseases. Nevertheless, there are also other studies implying that minocycline has no positive beneficial effects. Thus, the aim of the present study was to assess the preventive effect of minocycline against Aβ-induced changes in intrinsic electrophysiological properties in a rat model of AD. Methods: The present study extended this line of research by examining whether inhibition of microglial activation may alter the intrinsic electrophysiological properties of CA1 pyramidal neurons in a rat model of Aβ neurotoxicity, using whole cell patch clamp. Results: Findings showed that bilateral injection of the Aβ (1-42) into the prefrontal cortex caused membrane hyperpolarization, action potential (AP) narrowing and after hyperpolarization (AHP) amplitude enhancement. It was also resulted in a faster decay time of AP, higher rheobase current, lower firing frequency and smaller post stimulus AHP amplitude. Administration of minocycline (45mg/kg, i.p) not only failed to prevent Aβ-induced alterations in the intrinsic electrophysiological properties, but also enhanced the effects of Aβ on neuronal firing behavior. Conclusion: It can be concluded that minocycline, as a microglial inhibitor, may enhance the disruption of electrophysiological properties of CA1 pyramidal neurons induced by Aβ neurotoxin, including AP parameters and intrinsic neuronal excitability. Amyloid Beta (Aβ), Neurotoxicity, Minocycline, Microglial Cells, CA1 Pyramidal Neurons, Intrinsic properties 98 107 http://ppj.phypha.ir/browse.php?a_code=A-10-914-1&slc_lang=en&sid=1 Sharareh Daryani shararehdar@yahoo.com 3200319475328460016462 3200319475328460016462 No Neuroscience Research Centre and Dept. of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Evin, Tehran, Iran Alireza Farzaei alirezafarzaei@gmail.com 3200319475328460016463 3200319475328460016463 No Dept. of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran Narges Hosseinmardi nargeshosseinmardi@gmail.com 3200319475328460016464 3200319475328460016464 No Neuroscience Research Centre and Dept. of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Evin, Tehran, Iran Farideh Bahrami farideh_bahrami@yahoo.com 3200319475328460016465 3200319475328460016465 No Neuroscience Research Centre and Department of Physiology, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran Mahyar Janahmadi Janahmadi@sbmu.ac.ir 3200319475328460016466 3200319475328460016466 Yes Neuroscience Research Centre and Dept. of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Evin, Tehran, Iran