ObjectiveTo review the literature on psychological and biological findings on resilience (i.e. the successful adaptation and swift recovery after experiencing life adversities) at the level of the individual, and to integrate findings from animal and human studies.MethodElectronic and manual literature search of MEDLINE, EMBASE and PSYCHINFO, using a range of search terms around biological and psychological factors influencing resilience as observed in human and experimental animal studies, complemented by review articles and cross-references.ResultsThe term resilience is used in the literature for different phenomena ranging from prevention of mental health disturbance to successful adaptation and swift recovery after experiencing life adversities, and may also include post-traumatic psychological growth. Secure attachment, experiencing positive emotions and having a purpose in life are three important psychological building blocks of resilience. Overlap between psychological and biological findings on resilience in the literature is most apparent for the topic of stress sensitivity, although recent results suggest a crucial role for reward experience in resilience.ConclusionImproving the understanding of the links between genetic endowment, environmental impact and gene–environment interactions with developmental psychology and biology is crucial for elucidating the neurobiological and psychological underpinnings of resilience.

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The Goodpasture antigen-binding protein (GPBP) and its splice variant the ceramide transporter (CERT) are multifunctional proteins that have been found to play important roles in brain development and biology. However, the function of GPBP and CERT is controversial because of their involvement in two apparently unrelated research fields: GPBP was initially isolated as a protein associated with collagen IV in patients with the autoimmune disease Goodpasture syndrome. Subsequently, a splice variant lacking a serine-rich domain of 26 amino acids (GPBPD26) was found to mediate the cytosolic transport of ceramide and was therefore (re)named CERT. The two splice forms likely carry out different functions in specific sub-cellular localizations. Selective GPBP knockdown induces extensive apoptosis and tissue loss in the brain of zebrafish. GPBP/GPBPD26 knockout mice die as a result of structural and functional defects in endoplasmic reticulum and mitochondria. Because both mitochondria and ceramide play an important role in many biological events that regulate neuronal differentiation, cellular senescence, proliferation and cell death, we propose that GPBP and CERT are pivotal in neurodegenerative processes. In this review, we discuss the current state of knowledge on GPBP and CERT, including the molecular and biochemical characterization of GPBP in the field of autoimmunity as well as the fundamental research on CERT in ceramide transport, biosynthesis, localization, metabolism and cell homeostasis. Keywords: autoimmunity, ceramide, GPBP/CERT, neurodegenerative diseases. J. Neurochem. (2010) 113, 1369-1386. | 2010 | 113 | 1369-1386 doi: 10.1111/j.1471-4159.2010 (Raya et al. 1999). Goodpasture's syndrome is a strictly human disorder caused by antibodies directed against the non-collagenous domain of the a3-chain of collagen type IV [a3 (IV) NCI]. Collagen is a major component of the extracellular matrix. The autoantibodies cause rapid functional disruption of the basement membrane of lungs, kidneys and the choroid plexus (Salama et al. 2001). GPBP is a soluble extracellular protein which binds and phosphorylates the antigen in this syndrome. Its expression is increased in other spontaneous autoimmune disorders including Goodpasture's syndrome, lupus erythematosus, pemphigoid and lichen planus (Raya et al. 2000), suggesting that GPBP might be an important protein in autoimmune disorders, where autoantigens arise from abnormal protein domain organization. JOURNAL OF NEUROCHEMISTRYSubsequently, in 2003, Hanada and colleagues showed that a spliced variant of GPBP which lacks a serine-rich domain composed of 26 aa residues was responsible for the cytosolic trafficking of ceramide from the endoplasmic reticulum (ER), to the Golgi apparatus. Hence, this isoform was termed as CERT (Hanada et al. 2003). Since the longer isoform also has ceramide transport properties in vitro, GPBP was renamed as CERT L (Hanada et al. 2003).Thus far it is not clear how the extracellular function of GPBP/CERT L , which is related to immu...

The enzyme DNA methyltransferase 3a (Dnmt3a) is crucially involved in DNA methylation and recent studies have demonstrated that Dnmt3a is functionally involved in mediating and moderating the impact of environmental exposures on gene expression and behavior. Findings in rodents have suggested that DNA methylation is involved in regulating neuronal proliferation and differentiation. So far, it has been shown that chronic social defeat might influence neurogenesis, while susceptibility to social defeat stress is dependent on gene expression changes in the nucleus accumbens and the mesolimbic dopaminergic system. However, the role of Dnmt3a herein has not been fully characterized. Our earlier immunohistochemical work has revealed the existence of two types of Dnmt3a-immunoreactive cells in the mouse hippocampus, of which one represents a distinct type with intense Dnmt3a-immunoreactivity (Dnmt3a type II cells) co-localizing with a marker of recent proliferation. Based on this, we hypothesize that behavioral susceptibility to chronic social defeat stress is linked to (i) Dnmt3a protein levels in the nucleus accumbens and hippocampus, and (ii) to the density of Dnmt3a type II cells in the hippocampal dentate gyrus. While no differences were found in global levels of Dnmt3a protein expression in the nucleus accumbens and hippocampus, our stereological quantifications indicated a significantly increased density of Dnmt3a type II cells in the dentate gyrus of animals resilient to social defeat stress compared to susceptible and control animals. Further characterization of the Dnmt3a type II cells revealed that these cells were mostly doublecortin (25%) or NeuN (60%) immunopositive, thus defining them as immature and mature neurons. Moreover, negative associations between the density of Dnmt3a type II cells and indices of depressive-like behavior in the sucrose intake and forced swim test were found. These correlational data suggest that DNA methylation via Dnmt3a in the hippocampus co-regulates adaptivity of the behavioral response to chronic social defeat stress, and set the stage for further experimental studies testing a mediating role of Dnmt3a in experience-dependent plasticity, neurogenesis and (mal) adaptation to severe stressors.