Adverse effects of Δ9-tetrahydrocannabinol on neuronal bioenergetics during postnatal development
Ongoing societal changes in views on the medical and recreational roles of cannabis increased the use of concentrated plant extracts with a Δ9-tetrahydrocannabinol (THC) content of more than 90%. Even though prenatal THC exposure is widely considered adverse for neuronal development, equivalent experimental data for young age cohorts are largely lacking. Here, we administered plant-derived THC (1 or 5 mg/kg) to mice daily during P5-P16 and P5-P35 and monitored its effects on hippocampal neuronal survival and specification by high-resolution imaging and iTRAQ proteomics, respectively. We found that THC indiscriminately affects pyramidal cells and both cannabinoid receptor 1+ (CB1R)+ and CB1R- interneurons by P16. THC particularly disrupted the expression of mitochondrial proteins (complexes I-IV), a change that had persisted even 4 months after the end of drug exposure. This was reflected by a THC-induced loss of membrane integrity occluding mitochondrial respiration and could be partially or completely rescued by pH stabilization, antioxidants, bypassed glycolysis, and targeting either mitochondrial soluble adenylyl cyclase or the mitochondrial voltage-dependent anion channel. Overall, THC exposure during infancy induces significant and long-lasting reorganization of neuronal circuits through mechanisms that, in large part, render cellular bioenergetics insufficient to sustain key developmental processes in otherwise healthy neurons.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
|---|---|
| Enthalten in: |
JCI insight - 5(2020), 23 vom: 03. Dez. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Beiersdorf, Johannes [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
7J8897W37S |
|---|
| Anmerkungen: |
Date Completed 24.05.2021 Date Revised 24.05.2021 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1172/jci.insight.135418 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM317100297 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM317100297 | ||
| 003 | DE-627 | ||
| 005 | 20231225162524.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1172/jci.insight.135418 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1056.xml |
| 035 | |a (DE-627)NLM317100297 | ||
| 035 | |a (NLM)33141759 | ||
| 035 | |a (PII)135418 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Beiersdorf, Johannes |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Adverse effects of Δ9-tetrahydrocannabinol on neuronal bioenergetics during postnatal development |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 24.05.2021 | ||
| 500 | |a Date Revised 24.05.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Ongoing societal changes in views on the medical and recreational roles of cannabis increased the use of concentrated plant extracts with a Δ9-tetrahydrocannabinol (THC) content of more than 90%. Even though prenatal THC exposure is widely considered adverse for neuronal development, equivalent experimental data for young age cohorts are largely lacking. Here, we administered plant-derived THC (1 or 5 mg/kg) to mice daily during P5-P16 and P5-P35 and monitored its effects on hippocampal neuronal survival and specification by high-resolution imaging and iTRAQ proteomics, respectively. We found that THC indiscriminately affects pyramidal cells and both cannabinoid receptor 1+ (CB1R)+ and CB1R- interneurons by P16. THC particularly disrupted the expression of mitochondrial proteins (complexes I-IV), a change that had persisted even 4 months after the end of drug exposure. This was reflected by a THC-induced loss of membrane integrity occluding mitochondrial respiration and could be partially or completely rescued by pH stabilization, antioxidants, bypassed glycolysis, and targeting either mitochondrial soluble adenylyl cyclase or the mitochondrial voltage-dependent anion channel. Overall, THC exposure during infancy induces significant and long-lasting reorganization of neuronal circuits through mechanisms that, in large part, render cellular bioenergetics insufficient to sustain key developmental processes in otherwise healthy neurons | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Cell Biology | |
| 650 | 4 | |a Development | |
| 650 | 4 | |a Neurodevelopment | |
| 650 | 7 | |a Dronabinol |2 NLM | |
| 650 | 7 | |a 7J8897W37S |2 NLM | |
| 700 | 1 | |a Hevesi, Zsofia |e verfasserin |4 aut | |
| 700 | 1 | |a Calvigioni, Daniela |e verfasserin |4 aut | |
| 700 | 1 | |a Pyszkowski, Jakob |e verfasserin |4 aut | |
| 700 | 1 | |a Romanov, Roman |e verfasserin |4 aut | |
| 700 | 1 | |a Szodorai, Edit |e verfasserin |4 aut | |
| 700 | 1 | |a Lubec, Gert |e verfasserin |4 aut | |
| 700 | 1 | |a Shirran, Sally |e verfasserin |4 aut | |
| 700 | 1 | |a Botting, Catherine H |e verfasserin |4 aut | |
| 700 | 1 | |a Kasper, Siegfried |e verfasserin |4 aut | |
| 700 | 1 | |a Guy, Geoffrey W |e verfasserin |4 aut | |
| 700 | 1 | |a Gray, Roy |e verfasserin |4 aut | |
| 700 | 1 | |a Di Marzo, Vincenzo |e verfasserin |4 aut | |
| 700 | 1 | |a Harkany, Tibor |e verfasserin |4 aut | |
| 700 | 1 | |a Keimpema, Erik |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t JCI insight |d 2016 |g 5(2020), 23 vom: 03. Dez. |w (DE-627)NLM257703918 |x 2379-3708 |7 nnns |
| 773 | 1 | 8 | |g volume:5 |g year:2020 |g number:23 |g day:03 |g month:12 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1172/jci.insight.135418 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 5 |j 2020 |e 23 |b 03 |c 12 | ||