Maternal Deprivation in Rats Decreases the Expression of Interneuron Markers in the Neocortex and Hippocampus

Abstract

Early life stress has profound effects on the development of the central nervous system. We exposed 9-day-old rat pups to a 24 h maternal deprivation (MD) and sacrificed them as young adults (60-day-old), with the aim to study the effects of early stress on forebrain circuitry. We estimated numbers of various immunohistochemically defined interneuron subpopulations in several neocortical regions and in the hippocampus. MD rats showed reduced numbers of parvalbumin-expressing interneurons in the CA1 region of the hippocampus and in the prefrontal cortex, compared with controls. Numbers of reelin-expressing and calretinin-expressing interneurons were also reduced in the CA1 and CA3 hippocampal areas, but unaltered in the neocortex of MD rats. The number of calbinin-expressing interneurons in the neocortex was similar in the MD rats compared with controls. We analyzed cell death in 15-day-old rats after MD and found no difference compared to control rats. Thus, our results more likely reflect the downregulation of markers than the actual loss of interneurons. To investigate synaptic activity in the hippocampus we immunostained for glutamatergic and inhibitory vesicular transporters. The number of inhibitory synapses was decreased in the CA1 and CA3 regions of the hippocampus in MD rats, with the normal number of excitatory synapses. Our results indicate complex, cell type-specific, and region-specific alterations in the inhibitory circuitry induced by maternal deprivation. Such alterations may underlie symptoms of MD at the behavioral level and possibly contribute to mechanisms by which early life stress causes neuropsychiatric disorders, such as schizophrenia.

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

“…The reduction in PV + cellular density, observed in PrL is in line with the results of studies that employed a 3 h daily separation protocol during the first three postnatal weeks (Leussis et al, 2012;Ganguly et al, 2016;Grassi-Oliveira et al, 2016), as well as a previous result from our laboratory (Aksic et al, 2021). In another study, Helmeke et al (2008) reported an increase in the number of PV + neurons in the dorsal medial PFC of an adult Octogon degus which appeared strikingly opposite to our findings (Helmeke et al, 2008).…”

Sex Differences in Affective Dysfunction and Alterations in Parvalbumin in Rodent Models of Early Life Adversity

“…There is also evidence suggesting that ELA, specifically MS, may have a delayed impact on PV cell density. Brains that were collected immediately (or within a few days) after ELA experience generally had no significant differences in PV levels compared to control-rearing (Giachino et al, 2007 ; Brenhouse and Andersen, 2011 ; Soares et al, 2020 ; Richardson et al, 2021 ), while brains collected later in life (in adolescence and/or P40 and older) generally had decreased PV levels (Leussis et al, 2012 ; Wieck et al, 2013 ; Ganguly et al, 2015 ; Lukkes et al, 2017 , 2018 ; Kim et al, 2020 ; Aksic et al, 2021 ). Since PV cells have been found to increase significantly in number from juvenility to adolescence in brain regions such as the PFC (Caballero et al, 2014 ; Wu et al, 2014 ), it is possible that ELA may inhibit the maturational time course of PV cells.…”

Reelin Alterations, Behavioral Phenotypes, and Brain Anomalies in Schizophrenia: A Systematic Review of Insights From Rodent Models

“…Maternal deprivation models show usually impaired declarative memory and sensorimotor gating defects. Aksic et al (2021) reported a reduced number of RELN positive interneurons in the CA1 and CA3 regions of the hippocampus, but not in the neocortex. These anomalies were not caused by cell death, suggesting that maternal deprivation provokes a downregulation of RELN in offspring.…”

“… Aksic et al (2021) studied the effects of maternal deprivation in the expression of neocortex and hippocampus markers in P60 male and female rats. Maternal deprivation models show usually impaired declarative memory and sensorimotor gating defects.…”