Activation of androgen receptors alters hippocampal synaptic plasticity and memory retention through modulation of L-type calcium channels.

AIMS: It has been revealed that membrane androgen receptor activation modulates avoidance memory and synaptic plasticity. In a previous study, we showed that Calcineurin, a calcium dependent phosphatase, could be a potential mediator of these AR effects. Also, it is reported that AR activation leads to L-type calcium channel activation. The aim of the current study is to test whether L-type calcium channels are downstream of AR and whether this signal pathway mediates the impairment effect of androgenic steroids on passive avoidance memory and synaptic plasticity. MATERIALS AND METHODS: We measured the effect of Nandrolone Decanoate (AR agonist), AR antagonist (Nilutamide) plus ND or L-type calcium channel inhibitor (Nifedipine) plus ND on passive avoidance performance of adolescent male rats. For extracellular field potential recordings hippocampal slices were perfused with ND, Nilutamide-ND or Nifedipine-ND. KEY FINDINGS: Our results clarified that AR activation by ND could impair avoidance behavior as step through latency decreased in ND-treated group while application of both Nilutamide and Nifedipine reestablished normal avoidance behavior. Also, LTP induction in the CA1 area of hippocampus was diminished by ND perfusion and both AR antagonist and L-type calcium channel inhibitor application lead to normal LTP. These findings support our hypothesis that activation of L-type calcium channels are involved in ARs mechanism effects on both avoidance behavior and hippocampal synaptic plasticity. SIGNIFICANCE: Understanding the biological effects of AR agonists on cognitive processes and its cellular mechanism may be a new/supplementary way to treating fear-related disorders.

Protective Effects of Statins against Alzheimer Disease / 이화의대지

Alzheimer disease (AD) is a common neurodegenerative disorder, characterized by memory impairment, dementia, and diminished cognitive function. This disease affects more than 20 million people worldwide. Amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) are important pathological markers of AD. Multiple studies have indicated a potential association between elevated cholesterol levels and increased risk of AD, suggesting that lowering the cholesterol level could be a viable strategy for AD treatment or prevention. Statins, potent inhibitors of cholesterol synthesis, are widely used in clinical practice to decrease the plasma levels of LDL cholesterol in patients with hyperlipidemia. Statins are known to play a neuroprotective role in limiting Aβ pathology through cholesterol-lowering therapies. In addition to Aβ plaques and neurofibrillary tangles, the brains of AD patients exhibit signs of oxidative stress, neuroinflammatory responses, and synaptic disruption.Consequently, compounds with antioxidant, anti-inflammatory, and/or neuroprotective properties could be beneficial components of AD treatment strategies. In addition to lowering LDL cholesterol, statins have demonstrated therapeutic efficacy in various forms, including antioxidant, anti-inflammatory, and neuroprotective effects. These properties of statins are potential mechanisms underlying their beneficial effects in treating neurodegenerative diseases. Therefore, this review was conducted to provide an overview of the protective effects of statins against AD.