Postnatal binge‐like alcohol exposure decreases dendritic complexity while increasing the density of mature spines in mPFC Layer II/III pyramidal neurons

Abstract

Prenatal exposure to alcohol in humans can result in a wide range of deficits collectively referred to as Fetal Alcohol Spectrum Disorders. Of these deficits, cognitive impairments are among the most debilitating and long-lasting. Specifically, cognitive impairments in executive functioning suggest damage to the prefrontal cortex (PFC). Several external stimuli, such as morphine, chronic stress and maternal stress have been found to alter the dendritic structure of cells within the PFC. In this study, three groups of rat pups were used: intubated with alcohol (5.25g/kg/day; AE), sham intubated (SI), or suckle controls (SC) on PD4-9. On PD26-30 rats were anesthetized, perfused with saline and brains were processed for Golgi-Cox staining. Basilar dendrite complexity, spine density and spine phenotypes were evaluated for Layer II/III neurons in the medial PFC. Results indicate that AE rats have an altered basilar dendritic tree complexity due to a significant decrease in both length and number of intersections in proximity to the neuronal soma. Furthermore, spine density patterns of basilar dendrites remain unchanged while the density of mature versus immature spines significantly changes. These effects were not seen in the apical dendrites, indicating alcohol’s influence on different neuronal parts in a single cell. In addition, these results suggest that the innervations of the soma and basilar dendrites by thalamic projections may play a role. Thus, our data demonstrates that postnatal exposure to alcohol produces changes in the neuronal organization of rat adolescent PFC that may affect the performance on prefrontal-dependant behavioral tasks.

Activity and social behavior in a complex environment in rats neonatally exposed to alcohol

“…Such damage may contribute to the impaired impulse control and social deficits observed in children with FASD throughout life. In particular, rodent models of developmental alcohol exposure result in increased caspase-3 expression in the central nucleus of the amygdala (Mitchell & Snyder-Keller, 2003), long-term reductions to amygdalar opioid signaling (Lugo, Wilson, & Kelly, 2006), and altered synaptic connectivity and neuronal loss in the amygdala (Balaszczuk, Bender, Pereno, & Beltramino, 2011; Cullen et al, 2013; Zhou et al, 2010) and the prefrontal cortex (Hamilton, Whitcher, & Klintsova, 2010; Ikonomidou et al, 2000; Lawrence, Otero, & Kelly, 2012; Whitcher & Klintsova, 2008). Dysfunction of these brain areas could contribute to disruptions in social and play behavior observed in AE rats.…”

Impaired trace fear conditioning and diminished ERK1/2 phosphorylation in the dorsal hippocampus of adult rats administered alcohol as neonates.

“…Alcohol's teratogenic effects on forebrain development, the medial prefrontal cortex and hippocampus in particular, can be seen via reduced cell numbers (Livy et al, 2003;Mihalick et al, 2001) and constrained or altered spine density and dendritic complexity (Hamilton et al, 2010;Tanaka et al, 1991). Postnatal exposure is reported to diminish or alter hippocampal neurogenesis, stmctural plasticity, yV-methyl-D-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP), and CAl learning-dependent excitatory unit activity (Bonthius & West, 1991;Klintsova et al, 2007;Lindquist ct al, 2013;Livy et al, 2003;Puglia & Valenzuela, 2010).…”

Neonatal Ethanol Exposure Impairs Trace Fear Conditioning and Alters NMDA Receptor Subunit Expression in Adult Male and Female Rats

“…Neuroimaging studies have revealed structural and functional abnormalities in the hippocampus and prefrontal cortex of children with FASD (Davis et al, 2011), contributing to the impaired performance seen in both children and adults with FASD when tested in a variety of forebrain-dependent cognitive (e.g., learning and memory) tasks (Mattson et al, 2011). Ethanol (EtOH) exposure over postnatal days (PD) 4 to 9 in rodents, a period comparable to the human third trimester (Bayer et al, 1993), also impairs forebrain neurodevelopment, producing significant reductions in dendritic spine density, neurogenesis, and long-term potentiation (LTP) (Hamilton et al, 2010;Klintsova et al, 2007;Puglia and Valenzuela, 2010).…”