Serum amyloid A primes microglia for ATP-dependent interleukin-1\u3b2 release

Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves production of acute-phase proteins, including serum amyloid A (SAA). Interleukin-1\u3b2 (IL-1\u3b2), a master regulator of neuroinflammation produced by activated inflammatory cells of the myeloid lineage, in particular microglia, plays a key role in the pathogenesis of acute and chronic diseases of the peripheral nervous system and CNS. IL-1\u3b2 release is promoted by ATP acting at the purinergic P2X7 receptor (P2X7R) in cells primed with toll-like receptor (TLR) ligands

Efficient Subtractive Cloning of Genes Activated by Lipopolysaccharide and Interferon γ in Primary-Cultured Cortical Cells of Newborn Mice.

Innate immune responses play a central role in neuroprotection and neurotoxicity during inflammatory processes that are triggered by pathogen-associated molecular pattern-exhibiting agents such as bacterial lipopolysaccharide (LPS) and that are modulated by inflammatory cytokines such as interferon γ (IFNγ). Recent findings describing the unexpected complexity of mammalian genomes and transcriptomes have stimulated further identification of novel transcripts involved in specific physiological and pathological processes, such as the neural innate immune response that alters the expression of many genes. We developed a system for efficient subtractive cloning that employs both sense and antisense cRNA drivers, and coupled it with in-house cDNA microarray analysis. This system enabled effective direct cloning of differentially expressed transcripts, from a small amount (0.5 µg) of total RNA. We applied this system to isolation of genes activated by LPS and IFNγ in primary-cultured cortical cells that were derived from newborn mice, to investigate the mechanisms involved in neuroprotection and neurotoxicity in maternal/perinatal infections that cause various brain injuries including periventricular leukomalacia. A number of genes involved in the immune and inflammatory response were identified, showing that neonatal neuronal/glial cells are highly responsive to LPS and IFNγ. Subsequent RNA blot analysis revealed that the identified genes were activated by LPS and IFNγ in a cooperative or distinctive manner, thereby supporting the notion that these bacterial and cellular inflammatory mediators can affect the brain through direct but complicated pathways. We also identified several novel clones of apparently non-coding RNAs that potentially harbor various regulatory functions. Characterization of the presently identified genes will give insights into mechanisms and interventions not only for perinatal infection-induced brain damage, but also for many other innate immunity-related brain disorders

Parental imprisonment, child victimization and adult problems

This study addresses, in a Swedish sample, whether exposure to violence and/or crime during childhood, and mental health and/or behaviour problems as an adult, are overrepresented among young men and women who had a parent in prison at some time when they were a child. Results show that almost all the studied types of childhood victimization and adult problems were overrepresented, but verbal victimization, neglect, witnessing violence, Attention Deficit Hyperactivity Disorder (ADHD) and depression were significantly overrepresented. Although the associations between having a parent in prison and childhood victimization as well as having mental health and behaviour problems are weak, these results indicate that it is important for practitioners who meet such children to be aware that they are more likely than other children not only to suffer from mental health and/or behaviour problems but also to have experienced violence and/or neglect.</p

Typologies of Childhood Exposure to Violence: Associations With College Student Mental Health

Objective: This study examined typologies of childhood violence exposure (CVE) and the associations of profiles with current demographic characteristics and mental health in emerging adulthood. Participants: The study evaluated a sample of college students from 2 US geographic regions (Midwest, n = 195; Southeast, n = 200). Methods: An online questionnaire (collected 2013-2014) assessed CVE and current mental health. Latent class analysis was used to identify typologies of CVE. Follow-up analyses were conducted to distinguish differences between typologies in demographic characteristics and mental health. Results: Four distinct profiles emerged: High-Exposed, Domestic-Exposed, Community-Exposed, and Low-Exposed. High- and Domestic-Exposed groups were more likely to be first-generation college students and to experience symptoms of psychopathology. Conclusions: This study offers a unique presentation of CVE profiles and a nuanced interpretation of their differential relationship to current demographic characteristics and mental health. It may befit university mental health initiatives to engage first-generation students and utilize comprehensive assessments of previous victimization