Endoplasmic Reticulum Stress Contributes to the Loss of Newborn Hippocampal Neurons after Traumatic Brain Injury.

Adult hippocampal neurogenesis has been shown to be required for certain types of cognitive function. For example, studies have shown that these neurons are critical for pattern separation, the ability to store similar experiences as distinct memories. Although traumatic brain injury (TBI) has been shown to cause the loss of newborn hippocampal neurons, the signaling pathway(s) that triggers their death is unknown. Endoplasmic reticulum (ER) stress activates the PERK-eIF2α pathway that acts to restore ER function and improve cell survival. However, unresolved/intense ER stress activates C/EBP homologous protein (CHOP), leading to cell death. We show that TBI causes the death of hippocampal newborn neurons via CHOP. Using CHOP KO mice, we show that loss of CHOP markedly reduces newborn neuron loss after TBI. Injured CHOP mice performed significantly better in a context fear discrimination task compared with injured wild-type mice. In contrast, the PERK inhibitor GSK2606414 exacerbated doublecortin cell loss and worsened contextual discrimination. Administration of guanabenz (which reduces ER stress) to injured male rats reduced the loss of newborn neurons and improved one-trial contextual fear memory. Interestingly, we also found that the surviving newborn neurons in brain-injured animals had dendritic loss, which was not observed in injured CHOP KO mice or in animals treated with guanabenz. These results indicate that ER stress plays a key role in the death of newborn neurons after TBI. Further, these findings indicate that ER stress can alter dendritic arbors, suggesting a role for ER stress in neuroplasticity and dendritic pathologies.SIGNIFICANCE STATEMENT The hippocampus, a structure in the temporal lobe, is critical for learning and memory. The hippocampus is one of only two areas in which neurons are generated in the adult brain. These newborn neurons are required for certain types of memory, and are particularly vulnerable to traumatic brain injury (TBI). However, the mechanism(s) that causes the loss of these cells after TBI is poorly understood. We show that endoplasmic reticulum (ER) stress pathways are activated in newborn neurons after TBI, and that manipulation of the CHOP cascade improves newborn neuron survival and cognitive outcome. These results suggest that treatments that prevent/resolve ER stress may be beneficial in treating TBI-triggered memory dysfunction.

Visual cues for person-centered communication.

Nursing home communication is frequently limited and task-focused and fails to affirm resident personhood. We tested the feasibility and effects of automated digital displays of resident photographs to remind staff (N = 11) of resident (n = 6) personhood. Historical photographs were displayed in digital photo frames mounted in each resident's room. To evaluate the intervention's effects, staff-resident conversations were audio-recorded prior to displaying the frames and repeated 2 weeks and 3 months later. Conversations were transcribed and statements were topic coded (task-focused vs. interpersonal). Staff person-centered talk increased from 11% to 32% (z = 2.37, p = .02) after the intervention and task-talk decreased from 64% to 40%. Resident interpersonal topics increased from 20% to 37%. Staff statements increased from 29 at baseline, to 37 postintervention, and 41 at 3-month follow-up and resident engagement and reminiscence also increased. Effects were reduced after 3 months. Automated photo displays are an easily implemented, low-cost intervention to promote person-centered communication.