Aging and Lateralization of the Rat Brain on a Biochemical Level

Abstract

It has been suggested that the lateralization of the human brain underlies hemispheric specialization and that it can be observed also on a biochemical level. Biochemical laterality appears to be a basis of volumetric or functional asymmetry but direct relationships among them are still unclear. Moreover, age-related differences between the right and left hemispheres are not well documented in various rat strains. In the current study, biochemical markers sensitive to Alzheimer disease (activities of high-affinity choline uptake and of nitric oxide synthases, expression of 17beta-hydroxysteroid dehydrogenase type 10) were estimated in both hemispheres of young and old male Wistar/Long Evans rats. Our experiments indicate (1) differences in some biochemical markers between young Wistar and Long Evans rats (the activities of endothelial nitric oxide synthase are higher in Long Evans and those of citrate synthase in Wistar rats), (2) more similar brain asymmetry of healthy human/young Wistar brains when compared to those of young Long Evans, (3) the decrease in asymmetry of the physiologically left/right lateralized biomarker during aging (the activity of the high-affinity choline uptake decreases more markedly in the left side of old Wistar rats) in accordance with the HAROLD model, (4) the age-related shift to reversed left/right asymmetry of the physiologically right/left lateralized biomarker (the activity of inducible nitric oxide synthase increases especially in the left side of old Long Evans rats), and finally (5) age-related differences in physiologically unlateralized biomarkers between Wistar and Long Evans rats (changes in the activities of neural/endothelial nitric oxide synthases or in expression of 17beta-hydroxysteroid dehydrogenase type 10 are more asymmetrical in old Wistar when compared to rather bilateral alterations of old Long Evans animals). It seems that the physiological lateralization of the human or rat brains on a biochemical level and their age-related alterations are dependent on biomarker type/function. By our opinion, it is difficult, perhaps impossible, to make one simple universal model, at least on a biochemical level. Since lateral analyses are of sufficient sensitivity to reveal subtle links, we recommend using Wistar rather than Long Evans rats in modeling of diseases accompanied by alterations in brain asymmetry.

N-Methyl-d-Aspartate Receptor – Nitric Oxide Synthase Pathway in the Cortex of Nogo-A-Deficient Rats in Relation to Brain Laterality and Schizophrenia

“…Moreover, no individual young markedly lateralized (defined by an index of laterality greater than ±0.100) rat was identified. No asymmetrical differences in nNOS or eNOS activity were observed globally; however, in contrast to the NMDAR subunits, we found some lateralized individuals [namely, one-third of animals displayed marked R/L asymmetry of globally unlateralized nNOS/iNOS, one-third presented opposite L/R laterality, and only one-third was unlateralized, in accordance with our previous study (Krištofiková et al, 2010)]. On the other hand, young Sprague-Dawley males displayed pronounced R/L laterality in iNOS activity, similar to Wistar and Long Evans strains (Krištofiková et al, 2010).…”

“…We therefore recommended their use in animal models of various diseases that are accompanied by alterations in brain asymmetry. Knowledge of disease-mediated changes occurring in the human R and L hemisphere separately as well as that of brain lateralization of applied control animals (there are differences between mice and rats and also among various rodent strains) is necessary in validating animal models in this way (Krištofiková et al, 2004, 2008, 2010). Moreover, we have repeatedly found a very similar degree of brain asymmetry on a biochemical level in the hippocampus and cortex, two of the most asymmetrical brain regions (Krištofiková et al, 2010).…”

Osteopontin Expression during Early Cerebral Ischemia-Reperfusion in Rats: Enhanced Expression in the Right Cortex Is Suppressed by Acetaminophen

“…The right-specific laterality has also been demonstrated in rat studies of stress-related processes where medial prefrontal cortex output neurons demonstrated an intrinsic right brain specialization in both neuroendocrine and autonomic activation [34]. These differences have been proposed to have a biochemical basis [35].…”

Cerebrovascular hemodynamic correlates of aging in the Lou/c rat: A model of healthy aging

“…Hemispheric asymmetry is however much less documented in animal models. Biochemical markers were studied (Ramírez et al, 2004) and L/R asymmetry of cholinergic markers and their age dependence were found in various brain structures (Kristofiková et al, 2010;Kristofikova et al, 2004). We are not aware of any functional imaging study investigating response asymmetry in rats.…”