Id |
Subject |
Object |
Predicate |
Lexical cue |
T1166 |
132-417 |
Sentence |
denotes |
A proportion of glial fibrillary acidic protein (GFAP)-immunolabeled striatal astrocytes display punctate patterns of μ-opioid receptor (MOR) (a) and CCR5 (b) (43.8 ± 2.4%) immunofluorescence—with some faint immunoreactivity extending into the cell processes; scale bars = 10 μm (a-b). |
T1167 |
418-506 |
Sentence |
denotes |
HIV-1 Tat and morphine are no longer toxic to MSNs when CCR5 is deleted from glia (c-f). |
T1168 |
507-755 |
Sentence |
denotes |
In C57BL/J wild-type mixed glia-MSN co-cultures, Tat is neurotoxic (*p = 0.001 vs. controls), and co-exposure to morphine enhanced Tat-induced toxicity over a 72-h period (**p < 0.001 vs. controls, p < 0.05 vs. Tat) and antagonized by naloxone (c). |
T1169 |
756-830 |
Sentence |
denotes |
Naloxone or morphine by themselves had no effect on neuronal survival (c). |
T1170 |
831-1055 |
Sentence |
denotes |
In co-cultures with CCR5-deficit glia and wild-type neurons, exposure to Tat by itself is significantly toxic (*p < 0.001 vs. controls); however, the enhanced toxicity seen with combined morphine exposure was eliminated (d). |
T1171 |
1056-1178 |
Sentence |
denotes |
Unexpectedly, morphine co-treatment entirely abolished the toxic effects of Tat, restoring MSN survival to control levels. |
T1172 |
1179-1380 |
Sentence |
denotes |
Pre-treatment with naloxone re-established Tat toxicity, suggesting that the paradoxical protective effects of morphine are mediated by MOR (or perhaps another opioid receptor type) (d) (see Kim et al. |
T1173 |
1381-1387 |
Sentence |
denotes |
2018). |
T1174 |
1388-1513 |
Sentence |
denotes |
The neurotoxic patterns seen in CCR5-deficient MSNs and wild-type glial co-cultures are similar to wild-type co-cultures (e). |
T1175 |
1514-1641 |
Sentence |
denotes |
Co-cultures in which MSNs and glia are both deficient in CCR5 are similar to those in which CCR5 is only deficient in glia (f). |
T1176 |
1642-1768 |
Sentence |
denotes |
CCR5 deletion alters the expression and processing of BDNF precursor (pro-BDNF) to mature (mBDNF) by mixed-glial cultures (g). |
T1177 |
1769-2083 |
Sentence |
denotes |
BDNF is expressed by both astroglia and microglia; mBDNF is neuroprotective, while pro-BDNF can promote programmed cell death. mBDNF and pro-BDNF levels were analyzed in conditioned media from wild-type or CCR5-deficient mixed glia treated with Tat ± morphine after 6 h or 24 h to assess pro-BDNF and mBDNF levels. |
T1178 |
2084-2249 |
Sentence |
denotes |
The proportion of pro-BDNF/mBDNF levels was significantly higher in wild-type compared to CCR5-null glia at 24 h (lower row; g), suggesting reduced neuronal support. |
T1179 |
2250-2452 |
Sentence |
denotes |
Although morphine significantly decreased pro-BDNF in CCR5-deficient glia at both 6 h and 24 h compared to control levels (not shown), the pro-BDNF/mBDNF ratios were unaltered (upper and lower rows; g). |
T1180 |
2453-2691 |
Sentence |
denotes |
By contrast, combined Tat and morphine significantly decreased the pro-BDNF/mBDNF ratio at 6 h, suggesting transient protection with CCR5 deficiency that was not fully sustained at 24 h (p = 0.17) (*p < 0.05, wild-type vs. CCR5-null) (g). |
T1181 |
2692-2775 |
Sentence |
denotes |
Exogenous mBDNF is neuroprotective against combined Tat and morphine treatment (h). |
T1182 |
2776-2917 |
Sentence |
denotes |
Wild-type, mixed glial-MSN co-cultures were treated with mBDNF and Tat, or combined Tat and morphine (represented by dotted survival curves). |
T1183 |
2918-3038 |
Sentence |
denotes |
Tat alone was neurotoxic (*p < 0.05), and Tat was significantly worsened by co-exposing MSNs to morphine (**p < 0.0001). |
T1184 |
3039-3232 |
Sentence |
denotes |
The addition of mBDNF (50 ng/ml; 72 h) fully protected MSNs against combined Tat and morphine toxicity, but only tended to protect (albeit not significantly) MSNs treated with Tat alone (#)(h). |
T1185 |
3233-3536 |
Sentence |
denotes |
Overall, the results in c-h suggest (1) an important role for glial CCR5 in mediating HIV-1 and opiate neurotoxic interactions, (2) that CCR5 deficiency influences signaling through MOR, and (3) that CCR5 (and perhaps MOR) act via a BDNF intermediary to promote or obstruct neuronal survival (Kim et al. |
T1186 |
3537-3769 |
Sentence |
denotes |
2018). (a-b) Modified and reprinted with permission from Podhaizer et al. (2012). (c-h) Modified and reprinted from Kim et al. (2018), which is an open access article distributed under the terms of the Creative Commons CC BY license |