Acute Ethanol Exposure during Synaptogenesis Rapidly Alters Medium Spiny Neuron Morphology and Synaptic Protein Expression in the Dorsal Striatum

Abstract

Fetal alcohol spectrum disorders are caused by the disruption of normal brain development in utero. The severity and range of symptoms is dictated by both the dosage and timing of ethanol administration, and the resulting developmental processes that are impacted. In order to investigate the effects of an acute, high-dose intoxication event on the development of medium spiny neurons (MSNs) in the striatum, mice were injected with ethanol on P6, and neuronal morphology was assessed after 24 h, or at 1 month or 5 months of age. Data indicate an immediate increase in MSN dendritic length and branching, a rapid decrease in spine number, and increased levels of the synaptic protein PSD-95 as a consequence of this neonatal exposure to ethanol, but these differences do not persist into adulthood. These results demonstrate a rapid neuronal response to ethanol exposure and characterize the dynamic nature of neuronal architecture in the MSNs. Although differences in neuronal branching and spine density induced by ethanol resolve with time, early changes in the caudate/putamen region have a potential impact on the execution of complex motor skills, as well as aspects of long-term learning and addictive behavior.

Biomarkers of Affective Dysregulation Associated with In Utero Exposure to EtOH

“…Systemic treatment with a caspase inhibitor prevented both the dendritic spine pruning and the physiological deficit of LTD without interfering with the ongoing dopaminergic degeneration (discussed in [ 120 ]). In the present study, the increased levels of activated caspase-3 demonstrated in synaptosomes from EtOH-exposed fetuses are consistent with the known loss of brain volume and the cognitive disabilities of children with FAS [ 121 ] and the loss of dendritic spines previously shown in animal fetuses exposed to EtOH [ 122 , 123 ] and in human FAS [ 116 ]. Whether this involves monoaminergic neurons remains to be determined.…”

Alcohol and lactation: Developmental deficits in a mouse model

“…This is not surprising given that the prelimbic cortex is a region shown to play a role in alcohol-drinking reinforcement ( Engleman et al, 2020 ). These data are consistent with other brain areas (basal ganglia) where reductions in spine densities observed immediately after exposure seemed to reverse by 1 month of age ( Clabough et al, 2022 ). It is possible that alterations occurred in synaptogenesis and/or pruning earlier in the exposure period and recovered by weaning when the first measures were taken.…”

“…In early alcohol exposure models, acute exposures led to increased dendritic pruning in the prefrontal cortex, resulting in significant synapse loss (Socodato et al, 2020). Also, acute ethanol exposure during synaptogenesis (from P5 to P7) led to drastically decreased spine densities in the caudate/putamen, however, these densities recovered to normal levels by around P30 (Clabough et al, 2022).…”

Acute MPTP treatment decreases dendritic spine density of striatal medium spiny neurons via SNK‐SPAR pathway in C57BL/6 mice

“…Next, 6–8 MSNs were selected for each hemisphere, and 3 dendrites were selected per MSN for accuracy. The following criteria were used to select MSNs randomly: well‐impregnated neurons; clearly visible branches or other precipitates not obscured by other neurons; absence of visibly broken processes on the neuron; MSN visually resembled a typical medium spiny neuron (Clabough et al., 2021).…”