Long-Term Effects of Maternal Deprivation on Cholinergic System in Rat Brain

Abstract

Numerous clinical studies have demonstrated an association between early stressful life events and adult life psychiatric disorders including schizophrenia. In rodents, early life exposure to stressors such as maternal deprivation (MD) produces numerous hormonal, neurochemical, and behavioral changes and is accepted as one of the animal models of schizophrenia. The stress induces acetylcholine (Ach) release in the forebrain and the alterations in cholinergic neurotransmitter system are reported in schizophrenia. The aim of this study was to examine long-term effects of maternal separation on acetylcholinesterase (AChE) activity in different brain structures and the density of cholinergic fibers in hippocampus and retrosplenial (RS) cortex. Wistar rats were separated from their mothers on the postnatal day (P) 9 for 24 h and sacrificed on P60. Control group of rats was bred under the same conditions, but without MD. Brain regions were collected for AChE activity measurements and morphometric analysis. Obtained results showed significant decrease of the AChE activity in cortex and increase in the hippocampus of MD rats. Density of cholinergic fibers was significantly increased in CA1 region of hippocampus and decreased in RS cortex. Our results indicate that MD causes long-term structure specific changes in the cholinergic system.

Early‐life stress selectively affects gastrointestinal but not behavioral responses in a genetic model of brain–gut axis dysfunction

“…The mechanisms underlying the partial recovery of the cholinergic response are unclear following early-life stress; however, MS has previously been reported to differentially influence cholinesterase activity in the central nervous system. 44 Moreover, alterations in cholinergic sensitivity of WKY colon do not appear to persist following psychological stress. 26 The implication of a heightened response to cholinergic stimulation in the submucosa-mucosa of WKY rats exposed to MS remains to be determined.…”

“…Alternatively, adaptation of the colon to increased cholinergic stimulation, as a consequence of decreased cholinesterase activity in these animals, may account for the diminished response to bethanechol. The mechanisms underlying the partial recovery of the cholinergic response are unclear following early‐life stress; however, MS has previously been reported to differentially influence cholinesterase activity in the central nervous system . Moreover, alterations in cholinergic sensitivity of WKY colon do not appear to persist following psychological stress .…”

Why are maternally separated females inflexible? Brain activity pattern of COx and c-Fos

“…MS also leads to a reduction in dopamine receptors in CG, and administration of D1 agonists improves memory deficits caused by this dopamine reduction (Lejeune et al, 2013). In addition, adverse experiences in early development seem to lead to neuronal loss in CG (Arborelius & Eklund, 2007) and reductions in soma size (Marković et al, 2014).…”

“…However, comparing results from different laboratories is sometimes problematic due to variability in experimental designs. For instance, some research groups prefer maternal deprivation (MD), which involves separating the dam from the litter on postnatal day 9 (PND9) for 24 hours (Marković et al, 2014), whereas others prefer to separate repeatedly (i.e. 4 h/day PND 1-21 (Wang, Li, Du, Shao, & Wang, 2015) or for ten days (Felice et al, 2014).…”

Long-Term Effects of Maternal Deprivation on the Neuronal Soma Area in the Rat Neocortex

“…Hyde and Crook [ 42 ] proposed that focal pathological changes in either the prefrontal cortex or mesial temporal lobe could lead to neurochemical changes in multiple neurotransmitter systems such as dopaminergic, glutamatergic, and cholinergic. Recently, our group demonstrated region-specific changes in the activity of acetylcholine esterase (AChE) and density of cholinergic fibers as a result of perinatal maternal deprivation [ 43 ].…”