Changes of spine density and dendritic complexity in the prefrontal cortex in offspring of mothers exposed to stress during pregnancy

Abstract

Both chronic stress in adulthood and episodes of stress in the early postnatal period have been shown to interfere with neuronal development in limbic prefrontal cortical regions. The present study in rats showed for the first time that the development of layer II/III pyramidal neurons in the dorsal anterior cingulate (ACd) and orbitofrontal cortex (OFC) is significantly affected in offspring of mothers exposed to stress during pregnancy. In prenatally stressed (PS) male rat pups the ACd and OFC showed significantly lower spine densities on the apical dendrite (ACd, -20%; OFC, -25%), on basal dendrites reduced spine densities where found only in the OFC (-20% in PS males). Moreover, in both cortical areas a significant reduction of dendritic length was observed in PS males compared to control offspring, which was confined to the apical dendrites (ACd, -30%, OFC, -26%). Sholl analysis revealed that these alterations were accompanied by a significantly reduced complexity of the dendritic trees in both cortical regions. PS females displayed reductions of dendritic spine densities in the ACd and OFC on both the basal (ACd, -21%; OFC, -20%) and apical dendrites (ACd, -21%; OFC, -21%), however, in contrast to the findings in PS males, no dendritic atrophy was detected in the PS females. These findings demonstrate that gestational stress leads to significant alterations of prefrontal neuronal structure in the offspring of the stressed mothers in a sex-specific manner.

The Placenta as a Mediator of Stress Effects on Neurodevelopmental Reprogramming

“…Further, reduced synaptogenesis and hypo-myelination in limbic regions was found in male, but not in female, juvenile rats exposed to maternal stress (Murmu et al, 2006;Xu et al, 2013). Such changes appear to persist into adulthood, where, eg, decreased hippocampal cell proliferation and reduced dendritic length and complexity were detected in adult prenatally stressed male rats (Mandyam et al, 2008;Suenaga et al, 2012).…”

Development of cortical microstructure in the preterm human brain

“…Particular studies show that the length of basal dendrites, dendritic spine density, and synapse number at term are lower in frontal association cortex than in primary sensory or motor regions (22,23), and that the elongation of dendrites and the order of basal (but not apical) dendritic branching is complete at 38-40 wk postconception (24,25). Microstructural maturation can also be altered by perinatal stress, which leads to the retraction of apical dendrites (26).…”

Homers regulate drug-induced neuroplasticity: Implications for addiction

“…Transfection of this neuronal type with Homer1a, Homer1c or a mutant of Homer1c that interferes with the EVH1-binding domain on interacting proteins induces aberrant axonal projections and irregular dendritic arborization, while transfection with a mutant for Homer1a that does not interact with the EVH1-binding domain on interacting proteins prevented alterations in neuronal morphology and the alterations in axonal trajectories. Thus, there appears to be an optimal level of functional CC-Homer required in the growth cone for normal axonal pathfinding [221] and it is tempting to speculate that early environmental insults might alter Homer expression and produce abnormalities in neuronal orientation, morphology and axonal connections, as reported in the brains animals exposed prenatally to drugs of abuse or stress [e.g., 185,222]. 2,4,18,20,[224][225][226][227].…”

“…Stress is highly implicated in the etiology of addiction and stressors are considered major precipitating factors in relapse to drug-seeking and -taking [c.f., 152,153,222,[287][288][289][290][291][292][293][294][295]. Like repeated drug administration (see above), repeated exposure to stressors induces morphological abnormalities within glutamatergic pyramidal neurons within the cortex of laboratory animals [e.g., 184,221,[296][297][298].…”