Drebrin depletion alters neurotransmitter receptor levels in protein complexes, dendritic spine morphogenesis and memory-related synaptic plasticity in the mouse hippocampus.

Drebrin an actin-bundling key regulator of dendritic spine genesis and morphology, has been recently proposed as a regulator of hippocampal glutamatergic activity which is critical for memory formation and maintenance. Here, we examined the effects of genetic deletion of drebrin on dendritic spine and on the level of complexes containing major brain receptors. To this end, homozygous and heterozygous drebrin knockout mice generated in our laboratory and related wild-type control animals were studied. Level of protein complexes containing dopamine receptor D1/dopamine receptor D2, 5-hydroxytryptamine receptor 1A (5-HT1(A)R), and 5-hydroxytryptamine receptor 7 (5-HT7R) were significantly reduced in hippocampus of drebrin knockout mice whereas no significant changes were detected for GluR1, 2, and 3 and NR1 as examined by native gel-based immunoblotting. Drebrin depletion also altered dendritic spine formation, morphology, and reduced levels of dopamine receptor D1 in dendritic spines as evaluated using immunohistochemistry/confocal microscopy. Electrophysiological studies further showed significant reduction in memory-related hippocampal synaptic plasticity upon drebrin depletion. These findings provide unprecedented experimental support for a role of drebrin in the regulation of memory-related synaptic plasticity and neurotransmitter receptor signaling, offer relevant information regarding the interpretation of previous studies and help in the design of future studies on dendritic spines.

Severe anemia may not be a contraindication to debridement in a Jehovah's witness patient with necrotizng fasciitis of the lower extremity - A case report.

INTRODUCTION: Necrotizing fasciitis is a severe soft tissue infection characterized by rapidly progressing necrosis involving the fascia and subcutaneous tissue. Necrotizing fasciitis of the lower extremity in a Jehovah's Witness patient in the setting of severe anemia and systemic sepsis is uncommon. CASE PRESENTATION: A 62-year-old man of Jehovah's Witness faith with a history of alcohol use disorder and uncontrolled diabetes mellitus initially presented with a non-healing diabetic foot ulcer, subsequently developed sepsis and necrotizing fasciitis. He underwent an above the knee amputation and was transferred to our institution's Surgical Intensive Care Unit for further management. The patient presented in critical condition with a hemoglobin of 4.7 g/dL and progression of necrotizing fasciitis of the lower extremity stump. He underwent revision amputation and numerous excisional debridements along with IV antibiotics, epoetin alfa, and iron sucrose. He successfully recovered with minimal blood loss and was discharged with a hemoglobin of 8 g/dL. DISCUSSION: This case highlights some of the challenges involved in managing necrotizing fasciitis. The conversation with the Jehovah's Witness patient in a life-threatening condition must be held with the upmost respect. Surgical decision making and operative technique is critical in determining the boundary of excisional debridement to perform in the absence of the ability to transfuse blood. The medical management was focused on resuscitation for sepsis, severe anemia, hyperglycemia, and wound management. CONCLUSION: Severely anemic patients in critical condition can survive necrotizing fasciitis with a well-planned interdisciplinary approach without compromising patient autonomy.