Effects of developmental manganese, stress, and the combination of both on monoamines, growth, and corticosterone

Abstract

Developmental exposure to manganese (Mn) or stress can each be detrimental to brain development. Here, Sprague-Dawley rats were exposed to two housing conditions and Mn from postnatal day (P)4–28. Within each litter two males and 2 females were assigned to the following groups: 0 (vehicle), 50, or 100 mg/kg Mn by oral gavage every other day. Half the litters were reared in cages with standard bedding and half with no bedding. One pair/group in each litter had an acute shallow water stressor before tissue collection (i.e., standing in shallow water). Separate litters were assessed at P11, 19, or 29. Mn-treated rats raised in standard cages showed no change in baseline corticosterone but following acute stress increased more than controls on P19; no Mn effects were seen on P11 or P29. Mn increased neostriatal dopamine in females at P19 and norepinephrine at P11 and P29. Mn increased hippocampal dopamine at P11 and P29 and 5-HT at P29 regardless of housing or sex. Mn had no effect on hypothalamic dopamine, but increased norepinephrine in males at P29 and 5-HT in males at all ages irrespective of rearing condition. Barren reared rats showed no or opposite effects of Mn, i.e., barren rearing + Mn attenuated corticosterone increases to acute stress. Barren rearing also altered the Mn-induced changes in dopamine and norepinephrine in the neostriatum, but not in the hippocampus. Barren rearing caused a Mn-associated increase in hypothalamic dopamine at P19 and P29 not seen in standard reared Mn-treated groups. Developmental Mn alters monoamines and corticosterone as a function of age, stress (acute and chronic), and sex.

Manganese in teeth and neurobehavior: Sex-specific windows of susceptibility

“…The majority of studies examining the effect of Mn on neurobehavior have used rodents or non-human primates of male sex only, or have not stratified by sex (Beaudin et al 2016; Blecharz-Klin et al 2012; O’Neal et al 2014; Pappas et al 1997; Schneider et al 2009, 2013, 2015). In one recent study, female, but not male, Sprague-Dawley rats exposed to Mn during development had increased dopamine and norepinephrine in neostriatal tissue relative to controls (Vorhees et al 2014). However, another study found Mn-induced persistent neuronal morphologic changes in male mice striata, but not in females (Madison et al 2011).…”

Manganese Toxicity Upon Overexposure: a Decade in Review

“…They also observed an increased norepinephrine in the striatum and increased dopamine, NE, and serotonin levels in the hippocampus. By utilizing various ages of animals, these investigators reported that Mn exposure altered monoamines as a function of age [97]. …”

“…Very young animals as well as humans have increased intestinal Mn absorption [97] and also have increased accumulations of Mn in the CNS [108], due to increased permeability of neuronal barriers to Mn [34]. The young also have a reduced biliary excretion capacity [56].…”

Developmental manganese neurotoxicity in rats: Cognitive deficits in allocentric and egocentric learning and memory

“…This regimen increases blood and neostriatal Mn and alters monoamine neurotransmitters (Vorhees et al, 2014). FeD was induced using a diet with 90% less Fe than a standard diet.…”

“…Moreover, MnOE and FeD in combination increase body weight reductions and alter anxiety in rats compared to either factor alone (Amos-Kroohs et al, 2015). Developmental stress was induced using a barren cage procedure (Avishai-Eliner et al, 2001; Vorhees et al, 2014). Rats were placed in barren (BAR) cages from E7-P28, an interval spanning most of neurogenesis (Clancy et al, 2007).…”