Functional similarities between pigeon \u27milk\u27 and mammalian milk : induction of immune gene expression and modification of the microbiota

Pigeon ‘milk’ and mammalian milk have functional similarities in terms of nutritional benefit and delivery of immunoglobulins to the young. Mammalian milk has been clearly shown to aid in the development of the immune system and microbiota of the young, but similar effects have not yet been attributed to pigeon ‘milk’. Therefore, using a chicken model, we investigated the effect of pigeon ‘milk’ on immune gene expression in the Gut Associated Lymphoid Tissue (GALT) and on the composition of the caecal microbiota. Chickens fed pigeon ‘milk’ had a faster rate of growth and a better feed conversion ratio than control chickens. There was significantly enhanced expression of immune-related gene pathways and interferon-stimulated genes in the GALT of pigeon ‘milk’-fed chickens. These pathways include the innate immune response, regulation of cytokine production and regulation of B cell activation and proliferation. The caecal microbiota of pigeon ‘milk’-fed chickens was significantly more diverse than control chickens, and appears to be affected by prebiotics in pigeon ‘milk’, as well as being directly seeded by bacteria present in pigeon ‘milk’. Our results demonstrate that pigeon ‘milk’ has further modes of action which make it functionally similar to mammalian milk. We hypothesise that pigeon ‘lactation’ and mammalian lactation evolved independently but resulted in similarly functional products

Physical Interactions and Functional Relationships of Neuroligin 2 and Midbrain Serotonin Transporters

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) modulates many key brain functions including those subserving sensation, emotion, reward and cognition. Efficient clearance of 5-HT after release is achieved by the antidepressant-sensitive 5-HT transporter (SERT, SLC6A4). To identify novel SERT regulators, we pursued a proteomic analysis of mouse midbrain SERT complexes, evaluating findings in the context of prior studies that established a SERT-linked transcriptome. Remarkably, both efforts converged on a relationship of SERT with the synaptic adhesion protein neuroligin 2 (NLGN2), a postsynaptic partner for presynaptic neurexins, and a protein well known to organize inhibitory GABAergic synapses. Western blots of midbrain reciprocal immunoprecipitations confirmed SERT/NLGN2 associations, and also extended to other NLGN2 associated proteins (e.g. -neurexin (NRXN), gephyrin). Midbrain SERT/NLGN2 interactions were found to be Ca2+-independent, supporting cis versus trans-synaptic interactions, and were absent in hippocampal preparations, consistent with interactions arising in somatodendritic compartments. Dual color in situ hybridization confirmed co-expression of Tph2 and Nlgn2 mRNA in the dorsal raphe, with immunocytochemical studies confirming SERT:NLGN2 co-localization in raphe cell bodies but not axons. Consistent with correlative mRNA expression studies, loss of NLGN2 expression in Nlgn2 null mice produced significant reductions in midbrain and hippocampal SERT expression and function. Additionally, dorsal raphe 5-HT neurons from Nlgn2 null mice exhibit reduced excitability, a loss of GABAA receptor-mediated IPSCs, and increased 5-HT1A autoreceptor sensitivity. Finally, Nlgn2 null mice display significant changes in behaviors known to be responsive to SERT and/or 5-HT receptor manipulations. We discuss our findings in relation to the possible coordination of intrinsic and extrinsic regulation afforded by somatodendritic SERT:NLGN2 complexes

<i>Il1r1</i>^{<i>loxP/loxP</i>} Mice Exhibit Normal IL-1R1-Mediated Increases in Serum IL-6 Following IL-1α Injections.

<p>(A) WT and <i>Il1r1</i>^{<i>loxP/loxP</i>} animals exhibit significant and comparable serum IL-6 elevations 2 hrs after IL-1α injections (1 μg, i.p.), as compared to vehicle treated controls (two-way ANOVA, <i>P</i> < 0.0001 for treatment, genotype and their interaction, followed by post hoc Tukey’s multiple comparison tests, *** = <i>P</i> < 0.0001). IL-1α induced IL-6 elevations were found to be IL-1R1 dependent, as revealed by a lack of response in <i>Il1r1</i>^-/- animals. N = 4-6/group for all assays. (B) Excision of floxed <i>Il1r1</i> alleles by global Cre recombinase expression in <i>Il1r1</i>^{<i>loxP/loxP</i>} mice attenuates the ability of IL-1α treatment to increase serum IL-6 expression. No increases in IL-6 expression were found in IL-1α treated <i>Il1r1</i>^{<i>loxP/loxP</i>}:CMV Cre or <i>Il1r1</i>^<i>-/-</i> mice (one way ANOVA, <i>P</i> < 0.0001, followed by post hoc Tukey’s multiple comparison tests, *** = <i>P</i> < 0.0001) N = 5-7/group for all assays.</p