Chronic Ethanol Exposure Enhances Facial Stimulation-Evoked Mossy Fiber–Granule Cell Synaptic Transmission via GluN2A Receptors in the Mouse Cerebellar Cortex

Sensory information is transferred to the cerebellar cortex via the mossy fiber–granule cell (MF–GC) pathway, which participates in motor coordination and motor learning. We previously reported that chronic ethanol exposure from adolescence facilitated the sensory-evoked molecular layer interneuron–Purkinje cell synaptic transmission in adult mice in vivo. Herein, we investigated the effect of chronic ethanol exposure from adolescence on facial stimulation-evoked MF–GC synaptic transmission in the adult mouse cerebellar cortex using electrophysiological recording techniques and pharmacological methods. Chronic ethanol exposure from adolescence induced an enhancement of facial stimulation-evoked MF–GC synaptic transmission in the cerebellar cortex of adult mice. The application of an N-methyl-D-aspartate receptor (NMDAR) antagonist, D-APV (250 μM), induced stronger depression of facial stimulation-evoked MF–GC synaptic transmission in chronic ethanol-exposed mice compared with that in control mice. Chronic ethanol exposure-induced facilitation of facial stimulation evoked by MF–GC synaptic transmission was abolished by a selective GluN2A antagonist, PEAQX (10 μM), but was unaffected by the application of a selective GluN2B antagonist, TCN-237 (10 μM), or a type 1 metabotropic glutamate receptor blocker, JNJ16259685 (10 μM). These results indicate that chronic ethanol exposure from adolescence enhances facial stimulation-evoked MF–GC synaptic transmission via GluN2A, which suggests that chronic ethanol exposure from adolescence impairs the high-fidelity transmission capability of sensory information in the cerebellar cortex by enhancing the NMDAR-mediated components of MF–GC synaptic transmission in adult mice in vivo.

Traumatic Stress, Chronic Ethanol Exposure, or the Combination, Alter Cannabinoid System Components in Reward and Limbic Regions of the Mouse Brain

The cannabinoid system is independently affected by stress and chronic ethanol exposure. However, the extent to which co-occurrence of traumatic stress and chronic ethanol exposure modulates the cannabinoid system remains unclear. We examined levels of cannabinoid system components, anandamide, 2-arachidonoylglycerol, fatty acid amide hydrolase, and monoacylglycerol lipase after mouse single-prolonged stress (mSPS) or non-mSPS (Control) exposure, with chronic intermittent ethanol (CIE) vapor or without CIE vapor (Air) across several brain regions using ultra-high-performance liquid chromatography tandem mass spectrometry or immunoblotting. Compared to mSPS-Air mice, anandamide and 2-arachidonoylglycerol levels in the anterior striatum were increased in mSPS-CIE mice. In the dorsal hippocampus, anandamide content was increased in Control-CIE mice compared to Control-Air, mSPS-Air, or mSPS-CIE mice. Finally, amygdalar anandamide content was increased in Control-CIE mice compared to Control-Air, or mSPS-CIE mice, but the anandamide content was decreased in mSPS-CIE compared to mSPS-Air mice. Based on these data we conclude that the effects of combined traumatic stress and chronic ethanol exposure on the cannabinoid system in reward pathway regions are driven by CIE exposure and that traumatic stress affects the cannabinoid components in limbic regions, warranting future investigation of neurotherapeutic treatment to attenuate these effects.

Early Alcohol Withdrawal Reverses the Abnormal Levels of proBDNF/mBDNF and their Receptors

ObjectiveProlonged excessive ethanol intake impairs learning, memory and also causes brain atrophy. Brain-derived neurotrophic factor (BDNF) plays pivotal roles in the pathology of alcohol dependence. Our previous work found that chronic ethanol exposure altered the metabolism of BDNF, leading to the imbalance of proBDNF and mature BDNF (mBDNF). In this study, we hypothesized that early alcohol withdrawal would reverse the abnormal levels of proBDNF, mBDNF and their receptors.Method30 male alcohol dependence patients were recruited. Peripheral blood was sampled from all the subjects before and one week after alcohol withdrawal. The lymphocyte protein levels of proBDNF, p75NTR, sortilin and TrkB were analyzed by western blots and the serum level of mBDNF and TrkB was assayed by sandwich enzyme-linked immunosorbent assay (ELISA) at two different time points. ResultsThe levels of mBDNF and its receptor (TrkB) increased, oppositely the levels of proBDNF and its receptors (p75NTR and sortilin) decreased one week after alcohol withdrawal. ConclusionsEarly alcohol withdrawal reversed the abnormal levels of proBDNF, mBDNF and their receptors. The shift levels of proBDNF and mBDNF were both taken in the pathology of alcohol withdrawal.