Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "L773:1476 5578 "

Sökning: L773:1476 5578

Sortera/gruppera träfflistan
  • Arentsen, T., et al. (författare)
  • The bacterial peptidoglycan-sensing molecule Pglyrp2 modulates brain development and behavior
  • 2017
  • Ingår i: Molecular Psychiatry. - 1359-4184 .- 1476-5578. ; 22:2, s. 257-266
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies have revealed that the gut microbiota modulates brain development and behavior, but the underlying mechanisms are still poorly understood. Here, we show that bacterial peptidoglycan (PGN) derived from the commensal gut microbiota can be translocated into the brain and sensed by specific pattern-recognition receptors (PRRs) of the innate immune system. Using expression-profiling techniques, we demonstrate that two families of PRRs that specifically detect PGN (that is, PGN-recognition proteins and NOD-like receptors), and the PGN transporter PepT1 are highly expressed in the developing brain during specific windows of postnatal development in both males and females. Moreover, we show that the expression of several PGN-sensing molecules and PepT1 in the developing striatum is sensitive to manipulations of the gut microbiota (that is, germ-free conditions and antibiotic treatment). Finally, we used the PGN-recognition protein 2 (Pglyrp2) knockout mice to examine the potential influence of PGN-sensing molecules on brain development and behavior. We demonstrate that the absence of Pglyrp2 leads to alterations in the expression of the autism risk gene c-Met, and sex-dependent changes in social behavior, similar to mice with manipulated microbiota. These findings suggest that the central activation of PRRs by microbial products could be one of the signaling pathways mediating the communication between the gut microbiota and the developing brain.
  • Barbier, Estelle, et al. (författare)
  • Dependence-induced increase of alcohol self-administration and compulsive drinking mediated by the histone methyltransferase PRDM2
  • 2017
  • Ingår i: Molecular Psychiatry. - : NATURE PUBLISHING GROUP. - 1359-4184 .- 1476-5578. ; 22:12, s. 1746-1758
  • Tidskriftsartikel (refereegranskat)abstract
    • Epigenetic processes have been implicated in the pathophysiology of alcohol dependence, but the specific molecular mechanisms mediating dependence-induced neuroadaptations remain largely unknown. Here, we found that a history of alcohol dependence persistently decreased the expression of Prdm2, a histone methyltransferase that monomethylates histone 3 at the lysine 9 residue (H3K9me1), in the rat dorsomedial prefrontal cortex (dmPFC). Downregulation of Prdm2 was associated with decreased H3K9me1, supporting that changes in Prdm2 mRNA levels affected its activity. Chromatin immunoprecipitation followed by massively parallel DNA sequencing showed that genes involved in synaptic communication are epigenetically regulated by H3K9me1 in dependent rats. In non-dependent rats, viral-vector-mediated knockdown of Prdm2 in the dmPFC resulted in expression changes similar to those observed following a history of alcohol dependence. Prdm2 knockdown resulted in increased alcohol self-administration, increased aversion-resistant alcohol intake and enhanced stress-induced relapse to alcohol seeking, a phenocopy of postdependent rats. Collectively, these results identify a novel epigenetic mechanism that contributes to the development of alcohol-seeking behavior following a history of dependence.
  • Barchiesi, Riccardo, 1989-, et al. (författare)
  • An epigenetic mechanism for over-consolidation of fear memories
  • 2022
  • Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578.
  • Tidskriftsartikel (refereegranskat)abstract
    • Excessive fear is a hallmark of anxiety disorders, a major cause of disease burden worldwide. Substantial evidence supports a role of prefrontal cortex-amygdala circuits in the regulation of fear and anxiety, but the molecular mechanisms that regulate their activity remain poorly understood. Here, we show that downregulation of the histone methyltransferase PRDM2 in the dorsomedial prefrontal cortex enhances fear expression by modulating fear memory consolidation. We further show that Prdm2 knock-down (KD) in neurons that project from the dorsomedial prefrontal cortex to the basolateral amygdala (dmPFC-BLA) promotes increased fear expression. Prdm2 KD in the dmPFC-BLA circuit also resulted in increased expression of genes involved in synaptogenesis, suggesting that Prdm2 KD modulates consolidation of conditioned fear by modifying synaptic strength at dmPFC-BLA projection targets. Consistent with an enhanced synaptic efficacy, we found that dmPFC Prdm2 KD increased glutamatergic release probability in the BLA and increased the activity of BLA neurons in response to fear-associated cues. Together, our findings provide a new molecular mechanism for excessive fear responses, wherein PRDM2 modulates the dmPFC -BLA circuit through specific transcriptomic changes.
  • Bergen, S. E., et al. (författare)
  • Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder
  • 2012
  • Ingår i: Molecular Psychiatry. - 1359-4184 .- 1476-5578. ; 17:9, s. 880-886
  • Tidskriftsartikel (refereegranskat)abstract
    • Schizophrenia (SCZ) and bipolar disorder (BD) are highly heritable psychiatric disorders with overlapping susceptibility loci and symptomatology. We conducted a genome-wide association study (GWAS) of these disorders in a large Swedish sample. We report a new and independent case-control analysis of 1507 SCZ cases, 836 BD cases and 2093 controls. No single-nucleotide polymorphisms (SNPs) achieved significance in these new samples; however, combining new and previously reported SCZ samples (2111 SCZ and 2535 controls) revealed a genome-wide significant association in the major histocompatibility complex (MHC) region (rs886424, P = 4.54 x 10(-8)). Imputation using multiple reference panels and meta-analysis with the Psychiatric Genomics Consortium SCZ results underscored the broad, significant association in the MHC region in the full SCZ sample. We evaluated the role of copy number variants (CNVs) in these subjects. As in prior reports, deletions were enriched in SCZ, but not BD cases compared with controls. Singleton deletions were more frequent in both case groups compared with controls (SCZ: P = 0.003, BD: P = 0.013), whereas the largest CNVs (>500 kb) were significantly enriched only in SCZ cases (P = 0.0035). Two CNVs with previously reported SCZ associations were also overrepresented in this SCZ sample: 16p11.2 duplications (P = 0.0035) and 22q11 deletions (P = 0.03). These results reinforce prior reports of significant MHC and CNV associations in SCZ, but not BD.
Skapa referenser, mejla, bekava och länka
Typ av publikation
tidskriftsartikel (274)
forskningsöversikt (6)
konferensbidrag (1)
Typ av innehåll
refereegranskat (256)
övrigt vetenskapligt (25)
Sullivan, PF (37)
Landén, Mikael, 1966 (23)
Lichtenstein, P (17)
Larsson, Henrik, 197 ... (16)
Sklar, P (16)
Cichon, S. (16)
visa fler...
Rietschel, M (15)
O'Donovan, MC (15)
Owen, MJ (13)
Ripke, S (12)
Andreassen, OA (11)
Breen, G (11)
Corvin, A (11)
Rujescu, D (11)
Mattheisen, M (11)
Djurovic, S (10)
Stefansson, H. (10)
Wang, Y. (9)
Svenningsson, P (9)
Agartz, I (9)
Bulik, CM (9)
Boomsma, DI (9)
Zetterberg, Henrik, ... (9)
Craddock, N (9)
Gill, M. (9)
Hottenga, JJ (8)
Willemsen, G (8)
Kirov, G (8)
Muller-Myhsok, B (8)
Hultman, C (8)
Metspalu, A (8)
Leboyer, M. (8)
Kuja-Halkola, Ralf (8)
Mataix-Cols, David (8)
Nothen, MM (8)
Stefansson, K. (8)
Steinberg, S (7)
Penninx, BWJH (7)
Werge, T (7)
Crowley, JJ (7)
Hoffmann, P (7)
Jonsson, EG (7)
Milaneschi, Y. (7)
Palotie, A (7)
Kuja-Halkola, R. (7)
Lichtenstein, Paul (7)
Schalling, M (7)
Cervenka, Simon (7)
Rück, Christian (7)
Hultman, C. M. (7)
visa färre...
Karolinska Institutet (221)
Göteborgs universitet (45)
Uppsala universitet (37)
Örebro universitet (19)
Umeå universitet (13)
Linköpings universitet (11)
visa fler...
Stockholms universitet (8)
Lunds universitet (8)
Kungliga Tekniska Högskolan (3)
Mittuniversitetet (3)
Chalmers tekniska högskola (3)
Mälardalens universitet (1)
Högskolan i Skövde (1)
Södertörns högskola (1)
Linnéuniversitetet (1)
visa färre...
Engelska (281)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (111)
Naturvetenskap (18)
Samhällsvetenskap (6)


Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy