Antidepressant activity of pharmacological and genetic deactivation of the small-conductance calcium-activated potassium channel subtype-3.

RATIONALE: The voltage-insensitive, small-conductance calcium-activated potassium (SK) channel is a key regulator of neuronal depolarization and is implicated in the pathophysiology of depressive disorders. OBJECTIVE: We ascertained whether the SK channel is impaired in the chronic unpredictable stress (CUS) model and whether it can serve as a molecular target of antidepressant action. METHODS: We assessed the depressive-like behavioral phenotype of CUS-exposed rats and performed post-mortem SK channel binding and activity-dependent zif268 mRNA analyses on their brains. To begin an assessment of SK channel subtypes involved, we examined the effects of genetic and pharmacological inhibition of the SK3 channel using conditional knockout mice and selective SK3 channel negative allosteric modulators (NAMs). RESULTS: We found that [125I]apamin binding to SK channels is increased in the prefrontal cortex and decreased in the hippocampus, an effect that was associated with reciprocal levels of zif268 mRNA transcripts indicating abnormal regional cell activity in this model. We found that genetic and pharmacological manipulations significantly decreased immobility in the forced swim test without altering general locomotor activity, a hallmark of antidepressant-like activity. CONCLUSIONS: Taken together, these findings link depression-related neural and behavioral pathophysiology with abnormal SK channel functioning and suggest that this can be reversed by the selective inhibition of SK3 channels.

Older Adults With Cognitive and/or Physical Impairments Can Benefit From Immersive Virtual Reality Experiences: A Feasibility Study.

Background: Older adults living in long term care, rehabilitation hospitals, and seniors' residences often experience reduced mobility, sometimes resulting in confinement indoors and isolation, which can introduce or aggravate symptoms of depression, anxiety, loneliness, and apathy. As Virtual Reality (VR) technologies become increasingly accessible and affordable, there is a unique opportunity to enable older adults to escape their restricted physical realities and be transported to both stimulating and calming places which may improve their general well-being. To date no robust evaluations of the use of immersive VR therapy [experienced through a head-mounted-display (HMD)] for older adults within these settings have been reported. VR-therapy may prove to be a safe, inexpensive, non-pharmacological means of managing depressive symptoms and providing engagement and enjoyment to this rapidly growing demographic. Objectives: Establish whether it is feasible to use immersive VR technology as therapy for older adults who have reduced sensory, mobility and/or impaired cognition. This includes evaluation of tolerability, comfort, and ease of use of the HMD, and of the potential for immersive VR to provide enjoyment/relaxation and reduce anxiety and depressive symptoms. Methods: Sixty-six older adults (mean age 80.5, SD = 10.5) with varying cognitive abilities (normal = 28, mild impairment = 17, moderate impairment = 12, severe impairment = 3, unknown cognitive score = 6), and/or physical impairments, entered a multi-site non-randomized interventional study in Toronto, Canada. Participants experienced 3 to 20 min of 360°-video footage of nature scenes displayed on Samsung GearVR HMD. Data was collected through pre/post-intervention surveys, standardized observations during intervention, and post-intervention semi-structured interviews addressing the VR experience. Results: All participants completed the study with no negative side-effects reported (e.g., No dizziness, disorientation, interference with hearing aids); the average time spent in VR was 8 min and 76% of participants viewed the entire experience at least once. Participants tolerated the HMD very well; most had positive feedback, feeling more relaxed and adventurous; 76% wanted to try VR again. Better image quality and increased narrative video content were suggested to improve the experience. Conclusion: It is feasible and safe to expose older adults with various levels of cognitive and physical impairments to immersive VR within these settings. Further research should evaluate the potential benefits of VR in different settings (e.g., home/community based) and explore better customization/optimization of the VR content and equipment for the targeted populations.