Examination of cortically-projecting cholinergic neurons following exercise and environmental intervention in a rodent model of Fetal Alcohol Spectrum Disorders (FASD)
Date
2020
Authors
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Publisher
University of Delaware
Abstract
Background: 1 in 20 live births in the United States is exposed to alcohol prenatally, resulting in neurodevelopmental and behavioral deficits categorized under the umbrella clinical term, Fetal Alcohol Spectrum Disorders (FASD). Dietary choline supplementation has proven efficacious in animal model and clinical studies in ameliorating some of the cognitive deficits (for example: non-verbal intelligence and working memory) due to dysfunction of cholinergic neurotransmission resulting from prenatal alcohol exposure (Nguyen et al., 2016; Ryan et al., 2008a; Wozniak et al., 2020). Similarly, behavioral interventions upregulate cholinergic neurotransmission and rescue neuroanatomical and cognitive deficits in rodent models of FASD. This study examines the impact of two adolescent behavioral interventions (wheel running or “super-intervention”) on PFC cholinergic afferentation in a rodent model of FASD. ☐ Methods: The present study used immunocytochemical and histological tissue analysis techniques to examine the impacts of developmental alcohol exposure and two behavioral interventions (wheel running or “super intervention”) on cholinergic neuronal morphology in the Nucleus Basalis of Meynert-cortical cholinergic pathway. Tissue samples were collected at postnatal day (PD) 72 and samples from forty-seven male rodents were stained for choline acetyltransferase (ChAT+) in Nucleus Basalis of Meynert (NBM) and acetylcholinesterase (AChE+) in the prelimbic Cg2 sub-region of the medial prefrontal cortex in the present study. ChAT+ neuron number and volume and AChE+ axon number were quantified using unbiased stereology. ☐ Results: Our data indicate a main effect of postnatal treatment but not adolescent intervention on ChAT+ neuron number in the NBM on PD 72 (F(2, 38) = 4.689, p < 0.05, ηp2 = 0.20). Tukey’s HSD post hoc analysis confirms a significant reduction in ChAT+ neurons in AE (M = 1317.94, SEM = ±158.89) compared to SC (M = 2158.79, SEM = ±243.86) rodents on PD72 (p < 0.01). Neither postnatal treatment nor behavioral intervention had an effect on ChAT+ neuronal volume, NBM structural volume, AChE+ axon number or Cg2 structural volume on PD 72 (p > 0.05). ☐ Conclusions: Our study is the first to examine the cytoarchitectonics of cholinergic neurons along the NBM-cortical cholinergic pathway in adulthood following developmental AE and two behavioral interventions. We show that AE reduces the number of ChAT+ neurons in NBM and that this is not mitigated by either intervention. Sustained reduction of acetylcholine production in NBM, the primary cholinergic nucleus innervating the entire mammalian cortex, could account for some of the behavioral deficits associated with FASD pathology and may be a target of choline supplementation.
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Keywords
Cholinergic, Fetal Alcohol Spectrum Disorders, Intervention, Behavioral deficits, Behavioral interventions, Animal model