GPER was expressed by somatic and germ cells in normal adult human testes

in the hippocampus in rats that received the A 1-40/1-42 mixture. Of note is that, while exogenous A was injected into the hippocampus just to establish this model, its expression would not indicate the endogenous A level. Moreover, these same rats showed a lower expression of ChAT in the hippocampus, thalamus, and amygdala as compared with vehicle-treated rats. Since ChAT is an enzyme critical for acetylcholine synthesis, its downregulation suggests 10 Nociceptive Behavior and Leaning Impairment doi: 10.1371/journal.pone.0074533.g008 a loss of cholinergic neurons and a decrease in acetylcholine release indicative of an early pathological process in AD. Therefore, learning impairment induced by intra-hippocampal A injection mimics that demonstrated in preclinical models of AD. In the second experiment, intra-hippocampal injection of cycloheximide was used to examine whether disruption of learning and memory would influence the recovery of nociceptive behavior. Cycloheximide has been shown to inhibit protein synthesis in brain homogenates and disrupt learning and memory when administered to chicks in conjunction with a reminder treatment. The effect of cycloheximide on learning and memory consolidation is likely due to its role in blocking translation of polypeptide chains at the elongation and termination phases and provoking the accumulation of ribosome subunits on mRNA leading to inhibition of the protein synthesis. In this experiment, disruption of learning and memory was independently confirmed by the Morris water maze task in rats receiving cycloheximide, but not vehicle, injection into bilateral hippocampal CA1 area, which lasted for at least 19 days after the cycloheximide treatment. Concurrently, the recovery of nociceptive behavior was substantially shortened in those rats treated with cycloheximide, suggesting that the function of learning/memory is contributory to sustaining nociceptive behavior 10884437 in rats. It should be pointed out that chronic pain may contribute to deficits in working memory without alterations in long-term memory. Both models used in this study would affect memory beyond the working memory phase. Moreover, we did not specifically test performance of short versus long term memories. These issues merit further HC-030031 investigation in future studies. A number of studies have shown that a state of dysfunctional hippocampus such as that seen in AD due to A deposition could result in failure to recall the location of a hidden-platform in a water maze. Similar to the role of the hippocampus 17318643 in learning and memory, the amygdala participates in the translation of cognitive input into neuroendocrine activity as well. Accordingly, lesions of the amygdala and hippocampus produced emotional disturbances and learning impairment. On the other hand, thalamus is critical to the central processing of nociceptive signals. Consistent with an important functional role of hippocampus and amygdala in cognition and learning, our results indicate that the expression of NR1 and PKC was altered in these brain regions in rats with A-induced learning impairment. It is well known that an upregulated expression of the NMDA receptor and PKC is associated with persistent nociception due to the initiation of intracellular cascades through calcium influx. Importantly, several studies have shown a relationship between A and NMDA receptor activity as well. For example, 1) A increases excitotoxicity mediated by glutamate receptors including the NMDA re