Persistent sexually dimorphic effects of adolescent THC exposure on hippocampal synaptic plasticity and episodic memory in rodents.
Persistent sexually dimorphic effects of adolescent THC exposure on hippocampal synaptic plasticity and episodic memory in rodents.
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DOI：
10.1016/j.nbd.2021.105565
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发表时间：
2022-01
影响因子：
6.1
通讯作者：
Gall, Christine M.
中科院分区：
文献类型：
--
作者：
Le, Aliza A.;Quintanilla, Julian;Amani, Mohammad;Piomelli, Daniele;Lynch, Gary;Gall, Christine M.
关键词：
有证据表明，青春期吸食大麻会导致成年后的记忆和认知问题，但人们对生命早期接触大麻对突触操作的影响知之甚少，突触操作对于编码和组织信息至关重要。我们在这里报告，对青春期大鼠和小鼠（aTHC）进行为期 14 天的每日 Δ9-四氢大麻酚治疗，导致雌性和较小程度的雄性海马两个轴突系统的突触可塑性发生严重但选择性的缺陷（根据成年期的评估）。青少年接触 THC 不会改变基本的突触传递（输入/输出曲线），并且对频率促进仅产生适度的影响。然而，aTHC 严重损害了这两个物种的雌性和雄性小鼠侧向穿通路径中内源性大麻素依赖性的长期增强作用。这确实与依赖于侧向穿通路径功能的情景记忆成分的获取受损有关。仅在女性中，aTHC 治疗会破坏 Schaffer 连合 (S-C) 投射到 CA1 区域的增强，这与雌激素对 S-C 突触反应的影响不足和 CA1 依赖性空间（物体位置）记忆受损有关。所有结果都表明，aTHC 暴露对性别二态性和投射系统的特异性影响可能是生命早期大麻素使用对成人认知功能的离散影响的基础。此外，他们认为大麻使用的一些持久的、性别二态性的影响反映了突触雌激素作用的变化。
There is evidence that cannabis use during adolescence leads to memory and cognitive problems in young adulthood but little is known about effects of early life cannabis exposure on synaptic operations that are critical for encoding and organizing information. We report here that a 14-day course of daily Δ9-tetrahydrocannabinol treatments administered to adolescent rats and mice (aTHC) leads to profound but selective deficits in synaptic plasticity in two axonal systems in female, and to lesser extent male, hippocampus as assessed in adulthood. Adolescent-THC exposure did not alter basic synaptic transmission (input/output curves) and had only modest effects on frequency facilitation. Nevertheless, aTHC severely impaired the endocannabinoid-dependent long-term potentiation in the lateral perforant path in females of both species, and in male mice; this was reliably associated with impaired acquisition of a component of episodic memory that depends on lateral perforant path function. Potentiation in the Schaffer-commissural (S-C) projection to field CA1 was disrupted by aTHC treatment in females only and this was associated with both a deficit in estrogen effects on S-C synaptic responses and impairments to CA1-dependent spatial (object location) memory. In all the results demonstrate sexually dimorphic and projection system-specific effects of aTHC exposure that could underlie discrete effects of early life cannabinoid usage on adult cognitive function. Moreover they suggest that some of the enduring, sexually dimorphic effects of cannabis use reflect changes in synaptic estrogen action.
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影响因子：
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作者：
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通讯作者：
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