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Childhood traumatic events hamper the development of the hippocampus and impair declarative memory in susceptible individuals. Persistent elevations of hippocampal corticotropin-releasing factor (CRF), acting through CRF receptor 1 (CRF₁), in experimental models of early-life stress have suggested a role for this endogenous stress hormone in the resulting structural modifications and cognitive dysfunction. However, direct testing of this possibility has been difficult. In the current study, we subjected conditional forebrain CRF₁ knock-out (CRF₁-CKO) mice to an impoverished postnatal environment and examined the role of forebrain CRF₁ in the long-lasting effects of early-life stress on learning and memory. Early-life stress impaired spatial learning and memory in wild-type mice, and postnatal forebrain CRF overexpression reproduced these deleterious effects. Cognitive deficits in stressed wild-type mice were associated with disrupted long-term potentiation (LTP) and a reduced number of dendritic spines in area CA3 but not in CA1. Forebrain CRF₁ deficiency restored cognitive function, LTP and spine density in area CA3, and augmented CA1 LTP and spine density in stressed mice. In addition, early-life stress differentially regulated the amount of hippocampal excitatory and inhibitory synapses in wild-type and CRF₁-CKO mice, accompanied by alterations in the neurexin-neuroligin complex. These data suggest that the functional, structural and molecular changes evoked by early-life stress are at least partly dependent on persistent forebrain CRF₁ signaling, providing a molecular target for the prevention of cognitive deficits in adults with a history of early-life adversity.

Chronic stress evokes profound structural and molecular changes in the hippocampus, which may underlie spatial memory deficits. Corticotropin-releasing hormone (CRH) and CRH receptor 1 (CRHR1) mediate some of the rapid effects of stress on dendritic spine morphology and modulate learning and memory, thus providing a potential molecular basis for impaired synaptic plasticity and spatial memory by repeated stress exposure. Using adult male mice with CRHR1 conditionally inactivated in the forebrain regions, we investigated the role of CRH-CRHR1 signaling in the effects of chronic social defeat stress on spatial memory, the dendritic morphology of hippocampal CA3 pyramidal neurons, and the hippocampal expression of nectin-3, a synaptic cell adhesion molecule important in synaptic remodeling. In chronically stressed wild-type mice, spatial memory was disrupted, and the complexity of apical dendrites of CA3 neurons reduced. In contrast, stressed mice with forebrain CRHR1 deficiency exhibited normal dendritic morphology of CA3 neurons and mild impairments in spatial memory. Additionally, we showed that the expression of nectin-3 in the CA3 area was regulated by chronic stress in a CRHR1-dependent fashion and associated with spatial memory and dendritic complexity. Moreover, forebrain CRHR1 deficiency prevented the down-regulation of hippocampal glucocorticoid receptor expression by chronic stress but induced increased body weight gain during persistent stress exposure. These findings underscore the important role of forebrain CRH-CRHR1 signaling in modulating chronic stress-induced cognitive, structural and molecular adaptations, with implications for stress-related psychiatric disorders.

The company Carus-Verlag, founded in 1972 in Stuttgart, is a leading provider of sacred and secular choral music. With around 40 employees, the publishing house offers sheet music, audio productions, and practice apps for choir singers worldwide. Since 2020, Carus also offers digital downloads. The family-owned company focuses on publishing works by well-known composers such as Bach, Mendelssohn, and Schütz. [Extracted from the article]

Dementia affects one in ten adults over age 65. Paradoxically, dementia (e.g., Alzheimer's disease and related dementias) is underdiagnosed, with approximately 50% of those with dementia lacking a formal diagnosis. This limits options for care, support and research engagement. To address this gap, we developed and implemented a telehealth-based ECHO (Extension for Community Healthcare Outcomes) program, "Dementia 360," to provide education and support for clinicians and allied team members. We assessed the feasibility and acceptability of this telementoring educational offering and the effect it had on clinician confidence in diagnosing and treating dementia. Clinicians from across Oregon (n = 67) attended learning sessions via videoconferencing technology. The sessions, which focused on dementia diagnosis and treatment, included didactic information provided by experts, followed by case discussions. We assessed clinician acceptability using surveys, and confidence in identifying and treating those with dementia prior to and after Dementia 360 using paired t tests. Dementia 360 was acceptable to clinicians and significantly increased their comfort levels in identifying and treating those with dementia. The technology-based program provided support and instruction that was acceptable by clinicians, even those in frontier areas of the state. [ABSTRACT FROM AUTHOR]

The article presents a commentary on rapid deployment of a statewide COVID-19 Extension for Community Healthcare Outcomes (ECHO) Program for frontline clinicians. Topics include urgent need for the rapid dissemination of emerging public health and treatment best practices, scientific evidence, and available resources for rural clinicians; and ideal model for the rapid dissemination of pertinent information to rural clinicians during a crisis.