Wheel Running and Environmental Complexity as a Therapeutic Intervention in an Animal Model of FASD

Abstract

Aerobic exercise (e.g., wheel running (WR) extensively used in animal research) positively impacts many measures of neuroplastic potential in the brain, such as rates of adult neurogenesis, angiogenesis, and expression of neurotrophic factors in rodents. This intervention has also been shown to mitigate behavioral and neuroanatomical aspects of the negative impacts of teratogens (i.e., developmental exposure to alcohol) and age-related neurodegeneration in rodents. Environmental complexity (EC) has been shown to produce numerous neuroplastic benefits in cortical and subcortical structures and can be coupled with wheel running to increase the proliferation and survival of new cells in the adult hippocampus. The combination of these two interventions provides a robust "superintervention" (WR-EC) that can be implemented in a range of rodent models of neurological disorders. We will discuss the implementation of WR/EC and its constituent interventions for use as a more powerful therapeutic intervention in rats using the animal model of prenatal exposure to alcohol in humans. We will also discuss which elements of the procedures are absolutely necessary for the interventions and which ones may be altered depending on the experimenter's question or facilities.

Examination of cortically projecting cholinergic neurons following exercise and environmental intervention in a rodent model of fetal alcohol spectrum disorders

“…A minimum of 10 days of free access to running wheels is sufficient to induce neuroanatomical changes (Snyder, Glover, Sanzone, Kamhi, & Cameron, 2009). Previous studies conducted in the lab demonstrate that both WR and “super‐interventions” are sufficient to produce neuroanatomical alterations in our rodent model of FASD (Gursky & Klintsova, 2017; Hamilton et al, 2012, 2014).…”

“…The final third of animals began the “super‐intervention,” wheel running followed by exposure to a complex environment (WREC), on PD 30. WREC animals began in WR cages (described previously) where they had free access to running wheels until PD 42 when they were transferred to the highly stimulating environmentally complex (EC) cages, free access to running wheels followed by exposure to a complex environment, as described in Gursky and Klintsova (2017). Wheels were checked daily at 09:00 from PD 30–42 to measure the distance run.…”

“…Sections were then incubated in 0.1 mM acetylthiocholine medium ( (Gundersen, 1986;Sterio, 1984;West, Slomianka, & Gundersen, 1991;West, 2002). Neuronal volume estimation was quantified using the Nucleator probe in Ster-eoInvestigator software (Gundersen, 1988). For neuron number estimation, NBM was first manually outlined on all selected sections using a 5X objective and using the corpus callosum, striatum, and hippocampus as anatomical landmarks from Bregma −6.38 to −7.60 in accordance with the Paxinos and Watson Atlas (2014).…”

Environmental enrichment reverses increased addiction risk caused by prenatal ethanol exposure

“…So far, there are limited treatment options for PE-induced deficits (Murawski et al, 2015). Environmental intervention has been used to reduce impairments caused by PE (Gursky and Klintsova, 2017). Studies show that addictive behavior is influenced by rearing environments; an enriched environment (EE) can reduce addiction risk.…”

Introduction for the special issue on “exercise during pregnancy”

“…Milbocker and Klintsova (in this issue) considered the damage that alcohol exposure can inflict on cholinergic neurons and reasoned that behavioral interventions that upregulate cholinergic neurotransmission might help. They remind us that the “mammalian brain cholinergic system is the largest continuous aggregate of neurons in the central nervous system.” The rats exposed to alcohol during a rapid period of brain growth were presented as adults to running wheels that they voluntarily used (unlike most humans) followed by exposure to a complex environment where they could climb and enter all sorts of containers, tubes, and hammocks within a multi‐level cage combined with exposure to a changing assortment of colorful “toys” of all shapes and sizes (Gursky & Klintsova, 2017). The wheel running represents aerobic physical exercising while the complex environment could be considered brain exercising that might also enhance activity.…”