Effects of mindfulness-based stress reduction on neuropeptide Y plasma levels in stressed individuals

BACKGROUND: Clinical studies have suggested that dysregulation of the neuropeptide Y (NPY) system may play a role in psychiatric disorders, including chronic stress. Meanwhile, Mindfulness Based Stress Reduction (MBSR) has shown promise for stress-related maladies. However, no studies have explored whether MBSR can change plasma NPY concentration in stressed individuals.METHOD: Individuals with symptoms of chronic stress were randomly assigned to eight weeks of either MBSR (n = 15), a locally-developed stress reduction intervention (LSR) (n = 15) or a wait-list control group (n = 20). Blood samples were collected at baseline and at a twelve-week follow-up to determine the effects of MBSR or LSR compared to the wait-list control group on NPY levels.RESULTS: The MBSR group had increased plasma NPY levels after the program compared to the waitlist control group, whereas the LSR group was not statistically different from the other groups.CONCLUSION: This pilot study provides evidence of the feasibility of MBSR to alter plasma NPY.</p

Interaction with SORLA controls trafficking and synaptic exposure of TrkB.

<p>(<b>A</b>) Colocalization of endogenous SORLA (red) and TrkB (green) in primary cortical neurons as shown by confocal immunofluorescence microscopy. Scale bar: 10 µm. (<b>B</b>) Co-immunoprecipitation of endogenous SORLA and TrkB from brain lysates is seen using anti-SORLA (IP anti-SORLA; lane 2) and anti-Trk antisera (IP anti-TrkB; lane 3). Panel Input (lane 1) indicates presence of endogenous SORLA and TrkB in brain lysate prior to co-immunoprecipitation. Lane 4 indicates lack co-immunoprecipitation in the absence of primary antibody (No IgG). (<b>C</b>) SH-SY5Y neuroblastoma cells stably overexpressing SORLA (SY5Y-S) or parental control cells (SY5Y) were transfected with expression constructs for TrkB. Subsequently, proteins at the cell surface were biotinylated and immunoprecipitated using streptavidin beads. Western blot analysis documents reduced levels of biotinylated TrkB at the cell surface in SY5Y-S compared to SY5Y cells (panel Surface). Panel Input represents levels of TrkB and SORLA in cell lysates prior to precipitation. Detection of tubulin (tub.), β-integrin (β -integ.), and PDGF-β receptor (PDGF-R) served as controls for loading and immunoprecipitation, respectively. (<b>D</b>) Densitometric quantification of replicate Western blots as exemplified in (C) (n = 6, Student’s <i>t</i>-test). (<b>E</b>) Subcellullar fractionations of wild type and SORLA-deficient mouse brain extracts were probed for the indicated proteins using Western blot analysis. Elevated levels of TrkB receptors (pan-Trk antibody) are seen in the synaptosomal plasma membrane (pm) fraction in SORLA-deficient (lanes 7 and 8) as compared to control brains (lanes 5 and 6). In contrast, levels of Trk receptors in the postsynaptic density (PSD) are reduced in receptor-deficient (lane 10) compared with wild type brains (lane 9). Levels of Trk in total brain lysates prior to subcellular fractionation are similar between genotypes (lanes 1–4). Detection of synaptophysin (Synapt), AMPA receptors, and PSD95 served as respective loading controls. (<b>F</b>) Densitometric quantification of replicate Western blots as exemplified in (E) (n = 4–6, Student’s <i>t</i>-test).</p

Loss of SORLA aggravates neuromotoric deficits in Huntington’s disease mice.

<p>(<b>A</b>) At 10 weeks of age, Huntington’s disease mice deficient for SORLA (HD82x<i>Sorl1^−/−</i>) display aggravated hind limb clasping compared with HD82 control littermates (HD82x<i>Sorl1^+/+</i>). (<b>B, C</b>) Worsening of neuromotoric deficits due to loss of SORLA is also seen when comparing (HD82x<i>Sorl1^−/−</i>) animals with (HD82, <i>Sorl1^+/+</i>) controls of either sex at 10 (B) and 18 weeks of age (C) during consecutive days of rotarod performance test (n = 8–9, Mann-Whitney-U). (<b>D</b>) No difference in rotarod performance is seen comparing 10 weeks-old <i>Sorl1^+/+</i> and <i>Sorl1^−/−</i> mice matched for age and sex (n = 10, Mann-Whitney-U).</p

Selected list of proteins differentially regulated in SORLA-deficient versus wild type neurons following chronic BDNF application.

<p>The values indicate ratio of protein spot volume changes (increase ↑ or decrease ↓; ANOVA, p<0.05). Where applicable, data for different iso-spots of the same protein are given. n.a., not altered.</p

Reduced BDNF-dependent activation of TrkB in SORLA-deficient neurons.

<p>(<b>A, B</b>) Quantification of phosphorylated (p) forms of TrkB, Akt, and ERK in primary cortical neurons either non-treated (−) or treated with 150 ng/ml BDNF for 20 min (+) using Western blotting (A) and densitometric scanning of replicate blots (B). <i>Sorl1^−/−</i> neurons show reduced levels of pTrkB, pAKT, and pERK compared with <i>Sorl1^+/+</i> cells (n = 6–12, Mann-Whitney U test). (<b>C, D</b>) Quantification of total levels of TrkB, Akt, and ERK in primary neurons either non-treated (−) or treated with 150 ng/ml BDNF (+) for 20 min using Western blot (C) and densitometric scanning of replicate blots (D). Detection of tubulin (tub.) served as loading controls in A and C.</p