Age-Related Decrease in Stress Responsiveness and Proactive Coping in Male Mice.

Coping is a strategic approach to dealing with stressful situations. Those who use proactive coping strategies tend to accept changes and act before changes are expected. In contrast, those who use reactive coping are less flexible and more likely to act in response to changes. However, little research has assessed how coping style changes with age. This study investigated age-related changes in coping strategies and stress responsiveness and the influence of age on the processing of conditioned fear memory in 2-, 12- and 23-month-old male mice. Coping strategy was measured by comparing the escape latency in an active avoidance test and by comparing responses to a shock prod. The results showed that proactivity in coping response gradually decreased with age. Stress responsiveness, measured by stress-induced concentration of corticosterone, was also highest in 2-month-old mice and decreased with age. Consolidation of fear memory was highest in 12-month-old mice and was negatively correlated with the degree of stress responsiveness and proactivity in coping. Fear extinction did not differ among age groups and was not correlated with stress responsiveness or the proactivity of coping. However, the maintenance of extinct fear memory, which was best in 2-month-old mice and worst in 12-month-old mice, was negatively correlated with stress responsiveness but not with coping style. Age-dependent changes in the expression of glucocorticoid receptor (GR) and its regulatory co-chaperones, which are accepted mechanisms for stress hormone stimulation, were measured in the hippocampus. The expression of GR was increased at 12 months compared to other age groups. There were no differences in Hsp70 and BAG1 expression by age. These results can be summarized as follows: (1) stress responsiveness and proactivity in coping decreased with age class; (2) consolidation of fear memory was negatively correlated with both stress responsiveness and proactivity; however, maintenance of extinct fear memory was negatively correlated with stress responsiveness only; and (3) consolidation and maintenance of extinct fear memory appeared to be more influenced by factors other than stress reactivity and proactivity in coping, such as the amount of hippocampal glucocorticoid expression.

Nobiletin improves emotional and novelty recognition memory but not spatial referential memory.

How to maintain and enhance cognitive functions for both aged and young populations is a highly interesting subject. But candidate memory-enhancing reagents are tested almost exclusively on lesioned or aged animals. Also, there is insufficient information on the type of memory these reagents can improve. Working memory, located in the prefrontal cortex, manages short-term sensory information, but, by gaining significant relevance, this information is converted to long-term memory by hippocampal formation and/or amygdala, followed by tagging with space-time or emotional cues, respectively. Nobiletin is a product of citrus peel known for cognitive-enhancing effects in various pharmacological and neurodegenerative disease models, yet, it is not well studied in non-lesioned animals and the type of memory that nobiletin can improve remains unclear. In this study, 8-week-old male mice were tested using behavioral measurements for working, spatial referential, emotional and visual recognition memory after daily administration of nobiletin. While nobiletin did not induce any change of spontaneous activity in the open field test, freezing by fear conditioning and novel object recognition increased. However, the effectiveness of spatial navigation in the Y-maze and Morris water maze was not improved. These results mean that nobiletin can specifically improve memories of emotionally salient information associated with fear and novelty, but not of spatial information without emotional saliency. Accordingly, the use of nobiletin on normal subjects as a memory enhancer would be more effective on emotional types but may have limited value for the improvement of episodic memories.

Cordycepin Increases Nonrapid Eye Movement Sleep via Adenosine Receptors in Rats.

Cordycepin (3'-deoxyadenosine) is a naturally occurring adenosine analogue and one of the bioactive constituents isolated from Cordyceps militaris/Cordyceps sinensis, species of the fungal genus Cordyceps. It has traditionally been a prized Chinese folk medicine for the human well-being. Because of similarity of chemical structure of adenosine, cordycepin has been focused on the diverse effects of the central nervous systems (CNSs), like sleep regulation. Therefore, this study was undertaken to know whether cordycepin increases the natural sleep in rats, and its effect is mediated by adenosine receptors (ARs). Sleep was recorded using electroencephalogram (EEG) for 4 hours after oral administration of cordycepin in rats. Sleep architecture and EEG power spectra were analyzed. Cordycepin reduced sleep-wake cycles and increased nonrapid eye movement (NREM) sleep. Interestingly, cordycepin increased θ (theta) waves power density during NREM sleep. In addition, the protein levels of AR subtypes (A1, A2A, and A2B) were increased after the administration of cordycepin, especially in the rat hypothalamus which plays an important role in sleep regulation. Therefore, we suggest that cordycepin increases theta waves power density during NREM sleep via nonspecific AR in rats. In addition, this experiment can provide basic evidence that cordycepin may be helpful for sleep-disturbed subjects.