Effects of Maternal Deprivation on the Prefrontal Cortex of Male Rats: Cellular, Neurochemical, and Behavioral Outcomes

Abstract

Stressful events experienced during early life are associated with increased vulnerability of developing psychopathology in adulthood. In the present study, we exposed 9-day-old Wistar rats to 24 h maternal deprivation (MD) with the aim to investigate the impact of early life stress (ELS) on morphological, biochemical, and functional aspects of the prefrontal cortex (PFC), a brain region particularly sensitive to stress. We found that in the superficial medial orbital cortex (MO), young adult male rats had reduced density of GAD67 and CCK immunopositive cells, while the rostral part of the ventral lateral orbital cortex (roVLO) showed a decrease in the density of GAD67 immunopositive cells in both superficial and deep layers. In addition, the superficial rostral part of area 1 of the cingulate cortex (roCg1) and deep prelimbic cortex (PrL) was also affected by MD indicated by the reduction in PV immunopositive cellular density. Furthermore, MD induced upregulation of brain-derived neurotrophic factor (BDNF), while it did not affect the overall expression of Iba1 in neonatal or young adult PFC as measured by Western blot, however, microglial activation in young adult MD rats was detected immunohistochemically in deep layers of MO and infralimbic cortex (IL). Interestingly, when young adult male rats were subjected to a behavioral flexibility test in a T-maze, MD rats showed a subtle impairment in T-maze reversal learning indicating a mildly affected PFC function. Taken together, our findings demonstrated that MD reduced the density of interneurons and induced microglial activation, in particular, PFC areas at young adulthood, and could alter synaptic plasticity accompanied by PFC dysfunction.

The impact of early life maternal deprivation on the perineuronal nets in the prefrontal cortex and hippocampus of young adult rats

“…By performing the same stress protocol as in our previous studies ( Aksic et al, 2021 ; Poleksic et al, 2021 ), we confirmed the absence of changes in PV+ cell density after MD in the IL. However, to our surprise no significant changes in the PV interneuron density were detected in the roCg1 and PrL after MD.…”

“…Early life stress, such as maternal deprivation, affects the curve of PNNs development in the mPFC, by prolonging the low PNNs numbers and intensity state into the adulthood, possibly preventing stabilization of projected synapses on the PV+ interneurons (Sultana et al, 2021). This view is also supported by our recent findings of increased plasticity/stability ratio, indicated by higher BNDF expression in the PFC of neonatal and young adult MD rats (Poleksic et al, 2021).…”

“…These differences from our previous findings can be explained in part by using different microscopy and analysis approaches. Specifically, although using the same MD protocol, Poleksic et al, 2021 separated superficial from deep layers, and used a different scanning system (Axio Scan. Z1), and magnification (×20), while in this study deep and superficial layers were analyzed together and images were acquired at confocal laser scanning microscope (LSM 500), with ×40 magnification.…”

“…Previously, it has been found that 24 h MD reduces total neuron density in the PFC of young adult male rats ( Aksić et al, 2013 ). Furthermore, GABAergic cells are also affected in the hippocampus and PFC of MD rats in a subregion- and subpopulation-specific manner ( Aksic et al, 2021 ; Poleksic et al, 2021 ). Interestingly, morphological changes are accompanied by microglial activation, although a specific nature of glial response seems to differ between various models of early life stress ( Ferle et al, 2020 ; Wang et al, 2020 ; Poleksic et al, 2021 ) Apart from changes in neuronal and glial densities, MD leads to long–term functional deficits such as impairment in cognitive flexibility ( Baudin et al, 2012 ), recognition memory ( Marco et al, 2013 ), and social behavior ( Holland et al, 2014 ).…”

At the Crossroad Between Resiliency and Fragility: A Neurodevelopmental Perspective on Early-Life Experiences

“…According to the findings of accelerated maturation of limbic regions as a consequence of LBN and MS, it is reasonable to hypothesize a targeted increase of BDNF and IGF-1 in the cortico-limbic pathway. Two separate studies on MS-rats corroborate this hypothesis: one showing widespread cortical elevation of both BDNF and IGF-1 (Lee et al, 2012); another reporting elevated BDNF levels in the prefrontal cortex (Poleksic et al, 2021). In the amygdala, however, no significant changes in BDNF expression were observed .…”