Developmentally induced imbalance of dopaminergic fibre densities in limbic brain regions of gerbils ( Meriones unguiculatus )

Abstract

It is well established that epigenetic factors influence the maturation of neurotransmitter systems. Social isolation as well as an early intervention with methamphetamine (MA) lead to a diminished maturation of dopaminergic (DA) fibres in cortical and striatal areas in the brain of Mongolian gerbils. The aim of this study was to prove whether isolated rearing (IR) and the application of a single dose of MA on postnatal day 14 affect the maturation of DA fibres in caudal limbic areas. Therefore the DA fibre densities were quantified in the dorsolateral and ventrolateral entorhinal cortex (EC), the ventral subiculum (SUB) and in three amygdala nuclei - the basolateral (BLA), the lateral (LA) and the central (CA) nucleus. Our results showed that IR and an early MA application led to an increase of DA fibre densities in various caudal limbic areas. Whereas the BLA was affected by both IR and MA, the LA and the medial left CA were only influenced by MA in IR animals. The DA fibre surplus in the ventrolateral EC was significant in MA treated ER and IR animals in the left and right hemisphere, respectively. The SUB and the dorsolateral EC remained unaffected by both epigenetic factors. Altogether, the BLA seems to be the area which responds most sensitively to IR and MA. Previous studies in our laboratory showed a suppressive maturation of DA fibres in the prefrontal cortex (PFC) and nucleus accumbens (NAC) induced by the same set of epigenetic factors. Thus, due to the close functional connection between the PFC and limbic areas, it could be assumed that the suppressive maturation of prefrontal DA fibres implicates an enhancement of DA innervation densities in caudal limbic areas. Imbalances in the morphology and physiology of the different DA projections are suggested here to be crucial in the aetiology of schizophrenia.

Developmental neuroplasticity and the origin of neurodegenerative diseases

“…This leads to an aberrant maturation of prefrontal efferences to ipsiand contralateral parietal and limbic areas Witte et al 2007b) as well as behavioural abnormalities (Winterfeld et al 1998). In contrast to the hypoinnervation of the prefrontal cortex, dopaminergic, cholinergic and serotoninergic innervation of subcortical and limbic structures is enhanced (Busche et al 2002(Busche et al , 2004(Busche et al , 2006.…”

“…The maturation of dopaminergic fibre systems proceeds from caudal to rostral fields. There is first an excess of dopamine in motoric and limbic areas which is later reduced in favour of a higher dopaminergic innervation of the prefrontal cortex (dawirs et al 1993;Busche et al 2004;Teuchert-noodt 2006, 2007). full maturation of the prefrontal cortex is not reached until young adulthood (Kalsbeek et al 1988;Witte et al 2007a) and not till then a balance between the plastic events on the levels of the brainstem, striatum, limbic system and cortex is reached.…”

Effects of postweaning social and physical deprivation on locomotor activity patterns and explorative behavior in female CD‐1 mice

“…Based on the basal ganglia function of selective inhibition of motor activity on the one hand and the evidence of detrimental consequences of deprived housing on the underlying neural correlates on the other hand (Doya, 2000;Würbel, 2001), we predicted that physical and social deprivation would lead to increased general activity. Based on the functional correlation between amygdala stimulation and explorative activity in rodents on the one hand (Weingarten and White, 1978) and recent evidence of detrimental consequences of physical (and social) deprivation on the transmitter innervation (Busche et al, 2004) and progenitor proliferation in the amygdala (Okuda et al, 2009) on the other hand, we predicted that deprivation would lead to decreased exploratory behavior.…”

Rearing conditions and domestication background determine regulation of hippocampal cell proliferation and survival in adulthood – Laboratory CD1 and C57Bl/6 mice versus wild house mice

“…It is widely accepted that rearing rodents under deprivation of natural environmental stimulation causes severe impacts in the maturation of the prefrontal cortex-spanning from receptors (Melendez et al, 2004;Gregory and Szumlinski, 2008) and transmitters (Winterfeld et al, 1998;Brummelte et al, 2007) over structural alterations (Bagorda et al, 2006;Pascual et al, 2007;Fone and Porkess, 2008) to behavioural consequences (Winterfeld et al, 1998;Fone and Porkess, 2008;Gregory and Szumlinski, 2008)-as well as neurochemical changes in the limbic system (Busche et al, 2004;Galani et al, 2007;Fone and Porkess, 2008). Since the prefrontal cortex is reciprocally connected to the dentate gyrus via the entorhinal cortex, it might be reasonable that the imbalance between prefrontal and limbic activities also impacts the regulation of cell proliferation, differentiation and survival.…”

“…Especially in the phase after weaning, when an individual begins to independently interact with its social and physical environment, the maturation of relevant brain areas is under considerable influence of external factors. Deprivation or impoverishment of the necessary social and physical stimulation can lead to differences in behavioural and neuroplastic development especially in the prefrontal-limbic system (Winterfeld et al, 1998;Busche et al, 2004;Melendez et al, 2004;Bagorda et al, 2006;Brummelte et al, 2007;Galani et al, 2007;Pascual et al, 2007;Fone and Porkess, 2008). These impacts even seem to refer to adult neurogenesis in the hippocampal dentate gyrus, although the results remain contradictory: in gerbils, socially and physically deprived rearing increased rates of hippocampal cell proliferation in adulthood (Keller et al, 2000).…”