Lithium (Li+) is a drug widely employed for treating bipolar disorder, however the mechanism of action is not known. Here we study the effects of Li+ in cultured hippocampal neurons on a synaptic complex consisting of δ-catenin, a protein associated with cadherins whose mutation is linked to autism, and GRIP, an AMPA receptor (AMPAR) scaffolding protein, and the AMPAR subunit, GluA2. We show that Li+ elevates the level of δ-catenin in cultured neurons. δ-catenin binds to the ABP and GRIP proteins, which are synaptic scaffolds for GluA2. We show that Li+ increases the levels of GRIP and GluA2, consistent with Li+-induced elevation of δ-catenin. Using GluA2 mutants, we show that the increase in surface level of GluA2 requires GluA2 interaction with GRIP. The amplitude but not the frequency of mEPSCs was also increased by Li+ in cultured hippocampal neurons, confirming a functional effect and consistent with AMPAR stabilization at synapses. Furthermore, animals fed with Li+ show elevated synaptic levels of δ-catenin, GRIP, and GluA2 in the hippocampus, also consistent with the findings in cultured neurons. This work supports a model in which Li+ stabilizes δ-catenin, thus elevating a complex consisting of δ-catenin, GRIP and AMPARs in synapses of hippocampal neurons. Thus, the work suggests a mechanism by which Li+ can alter brain synaptic function that may be relevant to its pharmacologic action in treatment of neurological disease.
Background:While it is a rare entity, spinal angiolipomas are well-defined benign tumors that have been described sporadically in the literature starting from the late 1800s. Composed of mature lipomatous and angiomatous elements, these tumors manifest neurological symptoms due to progressive spinal cord or root compression. We present a case of a thoracic spinal angiolipoma and review the relevant literature.Case Description:A 68-year-old male with ongoing bilateral lower extremity weakness was found on enhanced magnetic resonance imaging to have an extradural mass in the thoracic spine causing cord compression. A T4–T8 laminectomy and complete excision of the epidural mass resulted in reversal of the patient's neurological symptoms. Histopathology identified the mass as a thoracic spinal angiolipoma.Conclusion:Given its uncommon occurrence and excellent prognosis, our report serves as a reminder to always consider spinal angiolipoma in the differential diagnosis of epidural masses.
We report the use of an upper extremity hemodialysis access site to facilitate endovascular treatment of the superior mesenteric artery in the setting of chronic mesenteric ischemia. A 64-year-old woman with end-stage renal disease on hemodialysis presented with worsening symptoms associated with chronic mesenteric ischemia. Her left upper extremity interposition graft within the fistula access site was selected to avoid a hostile aortoiliac system and in consideration of the potential benefits it provided over transfemoral, transbrachial, and transradial sites. The procedure was technically successful without complication. Hemodialysis access sites, such as the interposition graft within the fistula of this patient, are a potential route of upper extremity access for mesenteric interventions in patients with end-stage renal disease on hemodialysis.
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