Upload
h
View
213
Download
1
Embed Size (px)
Citation preview
receptor a/b gene expression ratio was decreased in mono-cytes of PP patients, strongly correlating with their immuneactivation. Further, we present results of the screening for CNSautoantibodies and altered tryptophan metabolism.Conclusion: This study demonstrates a robust dysregulation ofthe immuno-neuro-endocrine set point in postpartum psy-chosis.Financial support: This work was funded by MOODINFLAME –
Early diagnosis, treatment and prevention of mood disorderstargeting the activated inflammatory response system.
r e f e r e n c e s
1. Bergink V, Gibney SM, Drexhage HA. Autoimmunity,inflammation and psychosis: a search for peripheral markers.Biol Psych 2014;75(4):324–31.
2. Bergink V, Burgerhout KM, Weigelt K, Pop V, de Wit H,Drexhage RC, et al. Immune system dysregulation in first-onset postpartum psychosis. Biol Psych 2013;73(10):1000–7.
http://dx.doi.org/10.1016/j.npbr.2014.01.139
Analysis of single nucleotide polymorphisms in miRNAgenes and their role in schizophrenia etiology
P. Bolaños b, H. Raventós a,b,*
aSchool of Biology, University of Costa Rica, Costa RicabCenter for Research in Cellular and Molecular Biology, University ofCosta Rica, Costa Rica*Corresponding author.
Schizophrenia is a severe neuropsychiatric disease that inspite of having a clear genetic component in its etiology, thegenes involved have not yet been unequivocally identified andonly explain a small percentage of the cases. Within thecomplex scenario of gene expression regulation, microRNAshave been implicated in the post-transcriptional regulation ofmRNA. This mechanism of protein synthesis regulation hasbeen linked to the correct formation of synapses, whichtranslates in the ability to learn and other higher cognitivefunctions.Methods: miRNA candidate genes were established accordingto their genomic location and previous reports of differentialexpression in schizophrenic brains. Further in silico analysiswas carried out in order to establish the targets for miRNAregulation and their relationship to the pathology. SNPgenotyping analyses were performed in a sample of schizo-phrenic probands and their nuclear family members fromCosta Rica, in order to establish an association to diseasestatus.Results: A search of the available literature revealed a total of 60miRNA differentially expressed in brains of schizophrenicpatients, of which 12 were located in genomic regions ofinterest. Amongst the targets of posttranscriptional regulationare the Neurotrophin signaling pathways that have beenimplicated in important synaptic andneuronal processes. Thisresult strengthens the hypothesis that these miRNA can beinvolved in disease etiology. Of the 4 SNPs genotyped onlyrs41283391 on miR-195 was polymorphic in our sample,however the association to Schizophrenia diagnosis was notsignificant (n = 317, Z = 0.797, p = 0.42).Conclusion: This research project adds further information tothe hypothesis of the involvement of the miRNA regulationpathway in neuropsychiatric diseases. Even though theanalysis of these particular SNPs gave no evidence ofassociation, it is plausible that further sequence analysiscould reveal more information about variants that could
influence disease etiology. Another important outcome of thisproject is the establishment of further hypothesis for futureresearch projects, some of which are already underway.
http://dx.doi.org/10.1016/j.npbr.2014.01.140
The receptor–receptor interactions within the cytokinereceptor superfamily. Role in neuroinflammation andbeyond
D.O. Borroto-Escuela *, W. Romero-Fernandez,I. Brito, A.O. Tarakanov, D. Guidolin, L.F. Agnati, K. Fuxe
Department of Neuroscience, Karolinska Institutet, Stockholm,Sweden*Corresponding author.E-mail address: [email protected]
The mild encephalitis (ME) hypothesis of schizophrenia1
characterized a subgroup of severe psychiatric disorders inwhich low level neuroinflammation casually underlies thedisorder as the core pathogenic mechanism. This low levelneuroinflammation prevails and is important during a criticaltime period of diseases and it thought to be especially relevantin affective and schizophrenic disorders.2 The aetiologiesinvolved in low level neuroinflammation vary, includinginfections, autoimmunity, toxicity and trauma. The patho-logical mechanisms generally are linked to the interactionsbetween brain cells, immune cells and solutes resulting in aneffective inflammatory immune response (IIR). The IIR firstrequires the recruitment of cells to the site of inflammationand then their appropriate activation and regulation. Chemo-kines and cytokines are critical in these responses since theyare both chemotactic and immunoregulatory molecules.3
Cytokines are immunomodulating agents such as interleu-kins, interferons and chemokines which regulate the responseto infection, inflammation and trauma. Each cytokine has amatching cell-surface receptor which varies in their three-dimensional structure and cell type location. For instance, thecytokine receptor family comprises the Immunoglobulin (Ig)receptor superfamily, the Hemopoietic growth factor (type 1)receptor family, the interferon (type 2) receptor family, thetumor necrosis factor (TNF) (type 3) receptor family, theinterleukin-17 and -12 (IL-17 and IL-12) receptor family and theclass A G protein-coupled receptor chemokine receptor family.All these receptor-ligand pairs have a fundamental role inproviding directional cues for the immune cell trafficking andsignaling, both in the context of homeostasis and disease.4
However, immunomodulatory agents and their receptors arenot isolated entities, but instead function in complex networksinvolving homo- and heteroreceptor complexes formation aswell as crosstalk with other signaling cascades. For example,the arrest and chemotaxis of leukocytes during homeostasisand inflammation is an orchestrated phenomenon by amultitude of cytokines which are particularly adept atadjusting rapidly to changes within the environment. Theconfrontation of leukocytes with different combinations ofchemokines that are concomitantly produced under physio-logical or pathological conditions in vivo is a complexchallenge and receptor–receptor interaction in heteroreceptorcomplexes could be the molecular mechanisms behind thisphenomenon.5,6 In viral-induced disease receptor–receptorinteractions between viral and host-coded receptors can havea special relevance.7
Growing evidence indicates that the homo/heterodimericform is the basic functional structure of cytokine receptors.8
E-mail address: [email protected].
n e u r o l o g y , p s y c h i a t r y and b r a i n r e s e a r c h 2 0 ( 2 0 1 4 ) 3 – 2 76