Neural and Cognitive Markers and Regulation of Emotion in Depression: A Mini-Review and a Short Case Report

In the presented short clinical case of depression, the constructs of Research Domain Criteria (RDoC) of loss (negative valence systems) and cognitive control (cognitive systems) have been operationalized. It has been concluded that a normal cognitive control of emotion, requiring the functional and structural integrity of prefrontal cortex (PFC) and orbitofrontal cortex (OFC), is lacking in depression, but its amelioration can be achieved through the implementation of cognitive remediation/rehabilitation programs. A mini-review on neural and cognitive markers and regulation of emotion in depression is previously presented.

ARPE-19 conditioned medium promotes neural differentiation of adipose-derived mesenchymal stem cells

BACKGROUND Adipose-derived stem cells(ASCs)have been increasingly explored for cell-based medicine because of their numerous advantages in terms of easy availability,high proliferation rate,multipotent differentiation ability and low immunogenicity.In this respect,they have been widely investigated in the last two decades to develop therapeutic strategies for a variety of human pathologies including eye disease.In ocular diseases involving the retina,various cell types may be affected,such as Müller cells,astrocytes,photoreceptors and retinal pigment epithelium(RPE),which plays a fundamental role in the homeostasis of retinal tissue,by secreting a variety of growth factors that support retinal cells.AIM To test ASC neural differentiation using conditioned medium(CM)from an RPE cell line(ARPE-19).METHODS ASCs were isolated from adipose tissue,harvested from the subcutaneous region of healthy donors undergoing liposuction procedures.Four ASC culture conditions were investigated:ASCs cultured in basal Dulbecco's Modified Eagle Medium(DMEM);ASCs cultured in serum-free DMEM;ASCs cultured in serumfree DMEM/F12;and ASCs cultured in a CM from ARPE-19,a spontaneously arising cell line with a normal karyotype derived from a human RPE.Cell proliferation rate and viability were assessed by crystal violet and MTT assays at 1,4and 8 d of culture.At the same time points,ASC neural differentiation was evaluated by immunocytochemistry and western blot analysis for typical neuronal and glial markers:Nestin,neuronal specific enolase(NSE),protein gene product(PGP)9.5,and glial fibrillary acidic protein(GFAP).RESULTS Depending on the culture medium,ASC proliferation rate and viability showed some significant differences.Overall,less dense populations were observed in serum-free cultures,except for ASCs cultured in ARPE-19 serum-free CM.Moreover,a different cell morphology was seen in these cultures after 8 d of treatment,with more elongated cells,often showing cytoplasmic ramifications.Immunofluorescence results and western blot analysis were indicative of ASC neural differentiation.In fact,basal levels of neural markers detected under control conditions significantly increased when cells were cultured in ARPE-19 CM.Specifically,neural marker overexpression was more marked at 8 d.The most evident increase was observed for NSE and GFAP,a modest increase was observed for nestin,and less relevant changes were observed for PGP9.5.CONCLUSION The presence of growth factors produced by ARPE-19 cells in tissue culture induces ASCs to express neural differentiation markers typical of the neuronal and glial cells of the retina.

Globose basal cells for spinal cord regeneration

Spinal cord injury （SCI） is a devastating condition with loss of motor and sensory functions below the injury level. Cell based therapies are experimented in pre-clinical studies around the world. Neural stem cells are located intra-craniafly in subventricular zone and hippocampus which are highly invasive sourc- es. The olfactory epithelium is a neurogenic tissue where neurogenesis takes place throughout the adult life by a population of stem/progenitor cells. Easily accessible olfactory neuroepithelial stem/progenitor cells are an attractive cell source for transplantation in SCI. Globose basal cells （GBCs） were isolated from rat olfactory epithelium, characterized by flow cytometry and immunohistochemically. These ceils were further studied for neurosphere formation and neuronal induction. T10 laminectomy was done to create drop-weight SCI in rats. On the 9th day following SCI, 5 × 105 cells were transplanted into injured rat spinal cord. The outcome of transplantation was assessed by the Basso, Beattie and Bresnahan （BBB） locomotor rating scale, motor evoked potential and histological observation. GBCs expressed neural stem cell markers nestin, SOX2, NCAM and also mesenchymal stem cell markers （CD29, CD54, CD90, CD73, CD105）. These cells formed neurosphere, a culture characteristics of NSCs and on induction, differentiated cells expressed neuronal markers ~III tubulin, microtubule-associated protein 2, neuronal nuclei, and neurofilament. GBCs transplanted rats exhibited hindlimb motor recovery as confirmed by BBB score and gastrocnemius muscle electromyography amplitude was increased compared to controls. Green fluorescent protein labelled GBCs survived around the injury epicenter and differentiated into βⅢ tubulin-immunoreactive neuron-like cells. GBCs could be an alternative to NSCs from an accessible source for autologous neurotransplantation after SCI without ethical issues.