Maintenance of the Amygdala-Hippocampal Circuit Function with Safe and Feasible Shaking Exercise Therapy in SAMP-10 Mice

<b><i>Introduction:</i></b> Patients with dementia show reduced adaptive, behavioral, and physiological responses to environmental threats. Physical exercise is expected to delay brain aging, maintain cognitive function and, consequently, help dementia patients face threats and protect themselves skillfully. <b><i>Methods:</i></b> To confirm this, we aimed to investigate the effects of the shaking exercise on the avoidance function in the senescence-accelerated mouse-prone strain-10 (SAMP-10) model at the behavioral and tissue levels. SAMP-10 mice were randomized into 2 groups: a control group and a shaking group. The avoidance response (latency) of the mice was evaluated using a passive avoidance task. The degree of amygdala and hippocampal aging was evaluated based on the brain morphology. Subsequently, the association between avoidance response and the degree of amygdala-hippocampal aging was evaluated. <b><i>Results:</i></b> Regarding the passive avoidance task, the shaking group showed a longer latency period than the control group (<i>p</i> &#x3c; 0.05), even and low intensity staining of ubiquitinated protein, and had a higher number of and larger neurons than those of the control group. The difference between the groups was more significant in the BA region of the amygdala and the CA1 region of the hippocampus (staining degree: <i>p</i> &#x3c; 0.05, neuron size: <i>p</i> &#x3c; 0.01, neuron counts: <i>p</i> &#x3c; 0.01) than in other regions. <b><i>Conclusions:</i></b> The shaking exercise prevents nonfunctional protein (NFP) accumulation, neuron atrophy, and neuron loss; delays the aging of the amygdala and hippocampus; and maintains the function of the amygdala-hippocampal circuit. It thus enhances emotional processing and cognition functions, the memory of threats, the skillful confrontation of threats, and proper self-protection from danger.

Nrf2 Suppresses Oxidative Stress and Inflammation in App Knock-In Alzheimer’s Disease Model Mice

ABSTRACT Nrf2 (NF-E2-related-factor 2) is a stress-responsive transcription factor that protects cells against oxidative stresses. To clarify whether Nrf2 prevents Alzheimer’s disease (AD), AD model AppNL-G-F/NL-G-F knock-in (AppNLGF) mice were studied in combination with genetic Nrf2 induction model Keap1FA/FA mice. While AppNLGF mice displayed shorter latency to escape than wild-type mice in the passive-avoidance task, the impairment was improved in AppNLGF::Keap1FA/FA mice. Matrix-assisted laser desorption ionization–mass spectrometry imaging revealed that reduced glutathione levels were elevated by Nrf2 induction in AppNLGF::Keap1FA/FA mouse brains compared to AppNLGF mouse brains. Genetic Nrf2 induction in AppNLGF mice markedly suppressed the elevation of the oxidative stress marker 8-OHdG and Iba1-positive microglial cell number. We also determined the plasmalogen-phosphatidylethanolamine (PlsPE) level as an AD biomarker. PlsPE containing polyunsaturated fatty acids was decreased in the AppNLGF mouse brain, but Nrf2 induction attenuated this decline. To evaluate whether pharmacological induction of Nrf2 elicits beneficial effects for AD treatment, we tested the natural compound 6-MSITC [6-(methylsulfinyl)hexyl isothiocyanate]. Administration of 6-MSITC improved the impaired cognition of AppNLGF mice in the passive-avoidance task. These results demonstrate that the induction of Nrf2 ameliorates cognitive impairment in the AD model mouse by suppressing oxidative stress and neuroinflammation, suggesting that Nrf2 is an important therapeutic target of AD.

Impairment of Both Reward and Punishment Learning in Males Who Have Sexually Offended Against a Child

Prior studies suggest that persons with a sexual offense against a child (PSOCs) present with an impairment in learning from reinforcement, which may contribute to the behavioral dysregulation often seen in PSOCs. Therefore, gaining more insight into the nature of this impairment seems essential to better understand child sexual (re)offending. Using a passive avoidance task, we found that PSOCs ( n = 57) have difficulties with selecting behaviors that are associated with reward and suppressing behaviors that are associated with punishment relative to nonoffending men ( n = 33), but not compared with persons with a nonsexual offense history ( n = 31). The latter ability was particularly compromised in nonpedophilic PSOCs. By unraveling a source of pathology in the mechanisms that are involved in behavioral control, this study helps setting a step toward new, more tailored, therapeutic approaches.