Legislative Documents

Also, variously referred to as: Senate bills; Senate documents; Senate legislative documents; legislative documents; and General Court documents

Proliferation of oligodendroglia subpopulations following partial ON transection.

<p>Oligodendroglia and other olig2+ glia were identified with antibodies to NG2 (A), olig2 (B) and Ki67 (C), or with CC1 (E), olig2 (F) and Ki67 (G). D: Cells indicated are Ki67+/NG2+/olig2+ (>) and Ki67−/NG2+/olig2+ (>>). H: Cells indicated are Ki67+/CC1+/olig2+ (>) and Ki67−/CC1+/olig2+ (>>). Proliferating Ki67+/IBA1+ cells (I, indicated by >) and to a lesser extent Ki67+/GFAP+ cells (J) were observed after injury; representative examples at 3 days shown. K–P: Quantification of the mean density ± S.E of oligodendroglia and other olig2+ glia populations following partial transection. Densities of Ki67– cells are represented by black bars while densities of Ki67+ cells are represented by red bars and differences from control indicated by Δ(p≤0.05). Overall differences in total density (combined Ki67+ and Ki67– values) compared to control are indicated by *(p≤0.05). Q: Summary graph of Ki67+ mean densities of all oligodendroglia and other olig2+ glia subpopulations. Scale bar A–H: 20 µm, I–J: 10 µm.</p

Oligodendroglia subpopulations of varying maturity in adult control ON.

<p>A: Schematic diagram illustrates changes in the expression of NG2 and CC1 markers, and olig2 transcription factor across oligodendroglia subpopulations <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065710#pone.0065710-Nishiyama1" target="_blank">[24]</a>. Oligodendroglia and olig2+ glia were identified with combinations of antibodies to NG2 (B, D) and olig2 (C, D), or CC1 (E, G) and olig2 (F, G). D: Cells indicated are NG2+/olig2– (>), NG2+/olig2+ (>>) or NG2−/olig2+ (>l). G: Cells indicated are CC1+/olig2– (>) or CC1+/olig2+ (>>). H: Desmin+ cells (>) were not NG2+ (>>). Olig2 staining colocalises with Hoechst nuclear stain (I) and Nkx2.2+ nuclei (J). K: MBP+ myelin surrounds CC1+ oligodendrocyte somata. L: GFAP immunoreactivity surrounds some olig2+ nuclei (example >) but does not colocalise with CC1 (>>). M: Quantification of immunopositive oligodendroglia in control ON was expressed as the mean density of cells per mm² ± S.E. Scale bars: B–G: 20 µm, H–L: 10 µm.</p

Proportion of proliferating (Ki67+) cells that are immature oligodendroglia/CC1−/olig2+ glia.

<p>Data are expressed as percentages of the means ± SEM of data presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065710#pone-0065710-g002" target="_blank">Figs. 2K–M</a>. Note that values do not sum to 100% due to over-lapping populations.</p

Comparison of locomotor activity between offspring groups in response to a novel environment.

<p>Locomotor activity is shown on days 1–3, after saline or morphine administration on days 4–8 (10 mg/kg, s.c.), and after a final morphine challenge on day 16 (5 mg/kg, s.c.). A: Total activity scores in the vertical plane and B: in the horizontal plane, reveal that habituation was greater among naltrexone-exposed offspring. C: Total horizontal locomotor activity did not differ between groups treated with saline and challenged with morphine (saline-morphine). D: Total horizontal locomotor activity did not differ between groups treated with morphine, although sensitization was expressed in both groups after challenge with morphine (morphine-morphine). E: Analysis of data expressing total morphine-induced locomotor activity as a function of basal locomotor activity on day 3 revealed significantly greater activity values for naltrexone-exposed offspring, indicating an increased development of sensitization. Data are expressed as vertical plane entries (A) or horizontal distance moved in centimetres (B, C, D and E) and represent the mean ± SEM (one-way ANOVA: * <i>p</i><0.05, ** <i>p</i><0.01, *** <i>p</i><0.001; days 1–3 (A and B): placebo: n = 37, naltrexone: n = 53; days 4–16 (C): placebo: n = 12, naltrexone: n = 19; days 4–16 (D and E): placebo: n = 20, naltrexone: n = 26).</p

Myelin internode length following partial ON transection.

<p>Representative images of a single slice from the z stacks show ventral axons of control animals (A) and at 3 months following injury (B) anterogradely traced with CTB (green); paranodes are immunohistochemically labelled with Caspr and nodes with Nav1.6. C: The length of myelin internodes (indicated by <) under 110 µm were measured between paranodes (Caspr+ structures, red, confirmed by the presence of Nav1.6+ sodium channels, blue, at the node, indicated by brackets) and the data range, 25% and 75% percentile, median and mean (indicated by *) were displayed in the box plot. D: Mean number of internodes visible per FOV ± S.E (*p<0.05). Scale bar: 20 µm.</p

Comparison of naltrexone- and placebo-exposed offspring to progressive ratio morphine self-administration.

<p>Morphine self-administration under a progressive ratio (PR) schedule of 3–4 (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052812#pone-0052812-t001" target="_blank">Table 1</a> for response requirement) at a dose of 0.3 mg/kg/infusion. Data from the PR3–4 session are expressed as total active lever presses (A), breakpoint, defined as the final ratio completed within the 2 h session (B), and number of drug infusions (C) and represent the mean ± SEM (unpaired t-test, * <i>p</i><0.05, naltrexone versus placebo (n = 7). D: Cumulative response record for the PR3-4 session divided into 10 minute time bins. Data are expressed as number of active lever presses and represent mean ± SEM (two-way ANOVA, * <i>p</i><0.05, ** <i>p</i><0.01, naltrexone versus placebo (n = 7) for each time bin).</p

The effects of maternal naltrexone, or placebo, implants on offspring.

<p>The effects of maternal implant treatments during pregnancy on total litter size (observed live and still births), sex ratio of litters and term of pregnancy. Term refers to the length of pregnancy, measured in days. IQR = inter-quartile range. The mean and standard deviation (StdDev) are also shown (one-way ANOVA: ** <i>p</i><0.01, naltrexone versus placebo).</p

Instrumental requirement for PR9-4 and PR3-4 schedules.

<p>Lever response requirement values indicate the number of lever presses necessary for the acquisition of each subsequent infusion (infusion step number). Progressive increases vary between the two schedules such that for the 10^th infusion, 4 lever presses will result in an infusion using the PR9-4 schedule <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052812#pone.0052812-Grasing1" target="_blank">[42]</a>, whereas 32 lever presses are required for the 10^th infusion using PR3-4 schedule <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052812#pone.0052812-Roberts1" target="_blank">[43]</a>. Accordingly, the PR3-4 schedule is deemed more difficult as it progressively requires a greater lever response for an infusion than the PR9-4 schedule. Rat responding for morphine was assessed in the current study using both schedules.</p

Timeline and paradigm for operant self-administration experiment: offspring from cohort 3.

<p>Treatments are shown (oral sucrose training, morphine self-administration at 0.1 mg/kg/infusion dose, then at 0.3 mg/kg/infusion dose, period of abstinence, cue-induced drug-seeking), with corresponding schedule of reinforcement (FR1 and FR2, fixed ratio of 1 and 2, respectively; PR9-4 and PR3-4, progressive ratio 9-4 and 3–4, respectively [see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052812#pone-0052812-t001" target="_blank">Table 1</a>]; no schedule of reinforcement represented by ‘–’), and corresponding number of days for each treatment schedule (i.e. duration).</p