Deletion of GSK3? in D2R-Expressing Neurons Reveals Distinct Roles for ?-Arrestin Signaling in Antipsychotic and Lithium Action.

Deletion of GSK3? in D2R-expressing neurons reveals distinct roles for ?-arrestin signaling in antipsychotic and lithium action.

Filed under: Depression Treatment

Proc Natl Acad Sci U S A. 2012 Nov 27;
Urs NM, Snyder JC, Jacobsen JP, Peterson SM, Caron MG

Several studies in rodent models have shown that glycogen synthase kinase 3 ? (GSK3?) plays an important role in the actions of antispychotics and mood stabilizers. Recently it was demonstrated that GSK3? through a ?-arrestin2/protein kinase B (PKB or Akt)/protein phosphatase 2A (PP2A) signaling complex regulates dopamine (DA)- and lithium-sensitive behaviors and is required to mediate endophenotypes of mania and depression in rodents. We have previously shown that atypical antipsychotics antagonize DA D2 receptor (D2R)/?-arrestin2 interactions more efficaciously than G-protein-dependent signaling, whereas typical antipsychotics inhibit both pathways with similar efficacy. To elucidate the site of action of GSK3? in regulating DA- or lithium-sensitive behaviors, we generated conditional knockouts of GSK3?, where GSK3? was deleted in either DA D1- or D2-receptor-expressing neurons. We analyzed these mice for behaviors commonly used to test antipsychotic efficacy or behaviors that are sensitive to lithium treatment. Mice with deletion of GSK3? in D2 (D2GSK3?(-/-)) but not D1 (D1GSK3?(-/-)) neurons mimic antipsychotic action. However, haloperidol (HAL)-induced catalepsy was unchanged in either D2GSK3?(-/-) or D1GSK3?(-/-) mice compared with control mice. Interestingly, genetic stabilization of ?-catenin, a downstream target of GSK3?, in D2 neurons did not affect any of the behaviors tested. Moreover, D2GSK3?(-/-) or D1GSK3?(-/-) mice showed similar responses to controls in the tail suspension test (TST) and dark-light emergence test, behaviors which were previously shown to be ?-arrestin2- and GSK3?-dependent and sensitive to lithium treatment. Taken together these studies suggest that selective deletion of GSK3? but not stabilization of ?-catenin in D2 neurons mimics antipsychotic action without affecting signaling pathways involved in catalepsy or certain mood-related behaviors.
HubMed – depression

Early period psychiatric disorders following burn trauma and the importance of surgical factors in the etiology.

Filed under: Depression Treatment

Ulus Travma Acil Cerrahi Derg. 2012 Sep; 18(5): 436-40
Yabano?lu H, Ya?murdur MC, Ta?k?ntuna N, Karakayal? H

We aimed to assess early period psychiatric disorders following burn trauma.The files of 1369 patients who had burn trauma were analyzed retrospectively. Forty-five patients with the diagnosis of psychiatric disorder were assessed based on the variables of age, gender, presence of chronic diseases, psychiatric disorders prior to burn trauma, cause of the burn, burn percentage, degree of burn, additional trauma, number of surgeries, duration of hospitalization, extremity amputation, intubation status, psychiatric symptoms, post-trauma psychiatric disorders, and mortality.Forty-five patients developed psychiatric disorder in the early period following burn trauma. Of the 45 patients, 7 (15.5%) were female and 38 (84.5%) were male. The mean age was 32±14.3 years, burn percentage was 40.09±20.69%, number of operations was 2.95±1.75, and the total duration of hospitalization was 51.57±38.62 days. welve (26.6%) patients had post-traumatic stress disorder (PTSD), 11 (24.4%) had delirium, 8 (17.7%) had anxiety disorder, 7 (15.5%) had depression, 1 (2.2%) had abstinence syndrome, 1 (2.2%) had schizoaffective disorder, 2 (4.4%) had PTSD and depression, 2 (4.4%) had PTSD and delirium, and 1 (2.2%) had PTSD and anxiety disorder.Burn is a trauma that can be treated with a multidisciplinary approach.
HubMed – depression

Evolution of Nerve Injury with Unexpected EMG Signal Recovery in Thyroid Surgery Using Continuous Intraoperative Neuromonitoring.

Filed under: Depression Treatment

World J Surg. 2012 Nov 28;
Schneider R, Bures C, Lorenz K, Dralle H, Freissmuth M, Hermann M

BACKGROUND: Intermittent intraoperative neuromonitoring cannot prevent preparative surgical damage or predict imminent recurrent laryngeal nerve (RLN) damage with subsequent development of loss of electromyogram (EMG) signal during thyroid surgery. In case the nerve is stressed, i.e., from traction near the ligament of Berry, the nerve injury is only detected after it has occurred, not allowing the surgeon to correct the mechanical maneuver and salvage nerve function intraoperatively. METHODS: The unusual clinical scenario of sacrifice of a tumor-infiltrated RLN was used to study real-time evolution of RLN injury caused by mechanical distention. The ipsilateral vagus nerve (VN) was continuously stimulated with a new stimulation probe, and changes in EMG response were correlated with the varying levels of stretch and traction. RESULTS: Mechanical traction induced an intermittent depression of EMG amplitudes as a sign of impaired propagation of axon potentials or synaptic transmission. Prolonged mechanical stress caused a long-lasting depression of EMG response. When the mechanical distention was relieved, neurotransmission was gradually restored, with reappearance of singular muscle depolarization of full magnitude interspersed between the barely detectable deflections in the EMG recording. These responses of full amplitude appeared with increasing frequency, until the regular continuous EMG pattern was completely restored. CONCLUSIONS: Only continuous VN stimulation serves to detect early changes in EMG response that indicate imminent danger to RLN functional integrity and alerts the surgeon to immediately correctable surgical actions, thus possibly preventing nerve damage or transforming damage into a reversible event.
HubMed – depression

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