CREB Is Necessary for Synaptic Maintenance and Learning-Induced Changes of the Ampa Receptor GluA1 Subunit.

CREB is necessary for synaptic maintenance and learning-induced changes of the ampa receptor GluA1 subunit.

Hippocampus. 2013 Mar 18;
Middei S, Houeland G, Cavallucci V, Ammassari-Teule M, D’Amelio M, Marie H

The transcription factor cAMP response element binding protein (CREB) is a key protein implicated in memory, synaptic plasticity and structural plasticity in mammals. Whether CREB regulates the synaptic incorporation of hippocampal glutamatergic receptors under basal and learning-induced conditions remains, however, mostly unknown. Using double-transgenic mice conditionally expressing a dominant negative form of CREB (CREBS133A, mCREB), we analyzed how chronic loss of CREB function in adult hippocampal glutamatergic neurons impacts the levels of the AMPA and NMDA receptors subunits within the post-synaptic densities (PSD). In basal (naïve) conditions, we report that inhibition of CREB function was associated with a specific reduction of the AMPAR subunit GluA1 and a proportional increase in its Ser845 phosphorylated form within the PSD. These molecular alterations correlated with a reduction in AMPA receptors mEPSC frequency, with a decrease in long-term potentiation (LTP), and with an increase in long-term depression (LTD). The basal levels other major synaptic proteins (GluA2/3, GluN1, GluN2A, and PSD95) within the PSD were not affected by CREB inhibition. Blocking CREB function also impaired contextual fear conditioning (CFC) and selectively blocked the CFC-driven enhancement of GluA1 and its Ser845 phosphorylated form within the PSD, molecular changes normally observed in wild-type mice. CFC-driven enhancement of other synaptic proteins (GluA2/3, GluN1, GluN2A, and PSD95) within the PSD was not significantly perturbed by the loss of CREB function. These findings provide the first evidence that, in vivo, CREB is necessary for the specific maintenance of the GluA1 subunit within the PSD of hippocampal neurons in basal conditions and for its trafficking within the PSD during the occurrence of learning. © 2013 Wiley Periodicals, Inc. HubMed – depression



Depress Anxiety. 2013 Mar 15;
O’Donovan A, Rush G, Hoatam G, Hughes BM, McCrohan A, Kelleher C, O’Farrelly C, Malone KM

BACKGROUND: Patients with major depressive disorder (MDD) who attempt or complete suicide have elevated inflammation compared to nonsuicidal patients with MDD. However, greater severity of depression and the medical lethality of suicide attempts could account for such elevated inflammation in suicide attempters and suicide completers. METHODS: To clarify, we measured inflammatory markers in patients with MDD with and without high levels of suicidal ideation and in nondepressed controls (N = 124). Levels of suicidal ideation, depression severity, and recent suicide attempts were assessed by structured clinical interviews. A composite score including the inflammatory markers tumor necrosis factor-? (TNF-?), interleukin-6 (IL-6), interleukin-10 (IL-10), and C-reactive protein (CRP) was used as an inflammatory index. Analysis of covariance models were used to assess group differences with adjustments for age and gender. RESULTS: Patients with MDD and high suicidal ideation had significantly higher inflammatory index scores than both controls, F(1,53) = 18.08, partial ?(2) = .25, P < .001, and patients with MDD and lower suicidal ideation F(1,44) = 7.59, partial ?(2) = .15, P = .009. In contrast, patients with lower suicidal ideation were not significantly different from controls on the inflammatory index, F(1,63) = .52, partial ?(2) = .01, P = .47. Follow-up analyses indicated that differences between patients with MDD and high versus lower suicidal ideation were independent of depression severity and recent suicide attempts. CONCLUSIONS: Suicidal ideation may be uniquely associated with inflammation in depressed patients. HubMed – depression


Depressive Symptoms, Illicit Drug Use and HIV/STI Risk Among Sexual Minority Young Adults.

J Gay Lesbian Ment Health. 2013 Jan 11; 17(1): 96-102
Tolou-Shams M, Tarantino N, McKirnan DJ, Dyslin KJ

This study examined the interaction of depressive symptoms and drug use on HIV/STI risk among sexual minority young adults. Analyses tested the interactive effect of depressive symptoms and drug use on unprotected sex. Among drug users, more depressive symptoms were associated with higher rates of unprotected sex with a male partner (for both male and female participants) but this was non-significant for non-users. Interventions with these groups should incorporate content on depression and drug use to reduce HIV/STI risk. Prevention efforts also should not neglect the vulnerability of young women that have sex with women and/or identify as non-heterosexual. HubMed – depression



Ketamine A Quick Fix for Depression – Ketamine a tranquilizer used on large animals and a class-C drug may cause quick relief for severe depression.