Objective: We have analysed pharmacologically induced perturbation of functional and structural neurogenesis in the prefrontal cortex (PFC) and hippocampus. Method: Juvenile gerbils received a single dose of methamphetamine (METH, 50 mg/kg, i.p.). In adults the following parameters were quantitatively investigated: prefrontal dopaminergic and GABAergic innervation densities (immunocytochemistry), morphogenesis of pyramidal cells (Golgi), dentate granule cell proliferation (BrdU‐labelling), working memory and behavioural inhibition (delayed response, open‐field). Results: A single challenge of METH continuously suppresses granule cell proliferation in adult gerbils and initiates rewiring of neuronal networks in the PFC which run concurrently with the development of severe deficits in PFC‐related behaviours. Conclusion: It appears that a continuous remodelling of neuronal circuits is an inherent property of the brain, the biological significance of which seems to be to ascertain adaptive interaction between brain and environment. Learning more about drug‐induced neuronal reorganization might be basic for understanding the genesis of psychotic conditions in the brain. This presentation is based both on own research and on a review of the literature.
Based on developmental principles and insights from animal research about neuroplasticity in cell assemblies, this article is to propose a view of plasticity that promotes a link between hippocampal and prefrontal structure and function. Both the mitotic activity (counting of BrdU-labeled cells) in hippocampal dentatus and the maturation of dopamine fibres (quantitative immunochemistry of mesoprefrontal projection) in the prefrontal cortex proved to be a measurable combination for investigating the complex chain of events that relate activity dependent neuroplasticity to normal as well as to pathological maturational processes. With our animal model we demonstrate that both rearing conditions and neuroactive substances can effectively interfere with developmental plasticity and induce a malfunctional adaptation of prefrontal structures and neurotransmitter systems (dopamine, GABA). In the hippocampal dentatus, where ontogenetic plasticity proved to be preserved by continued neuro-and synaptogenesis, serious damage can be internalized without simultaneous disruption of neural dynamics offering an approach to reverse dysfunctional reorganization in the prefrontal cortex.
Abstract Background The aim of the study was to test long-term effects of (+)-methamphetamine (MA) on the dopamine (DA) innervation in limbo-cortical regions of adult gerbils, in order to understand better the repair and neuroplasticity in disturbed limbic networks. Methods Male gerbils received a single high dose of either MA (25 mg/kg i.p.) or saline on postnatal day 180. On postnatal day 340 the density of immunoreactive DA fibres and calbindin and parvalbumin cells was quantified in the right hemisphere. Results No effects were found in the prefrontal cortex, olfactory tubercle and amygdala, whereas the pharmacological impact induced a slight but significant DA hyperinnervation in the nucleus accumbens. The cell densities of calbindin (CB) and parvalbumin (PV) positive neurons were additionally tested in the nucleus accumbens, but no significant effects were found. The present results contrast with the previously published long-term effects of early postnatal MA treatment that lead to a restraint of the maturation of DA fibres in the nucleus accumbens and prefrontal cortex and a concomitant overshoot innervation in the amygdala. Conclusion We conclude that the morphogenetic properties of MA change during maturation and aging of gerbils, which may be due to physiological alterations of maturing vs. mature DA neurons innervating subcortical and cortical limbic areas. Our findings, together with results from other long-term studies, suggest that immature limbic structures are more vulnerable to persistent effects of a single MA intoxication; this might be relevant for the assessment of drug experience in adults vs. adolescents, and drug prevention programs.
Adrenal steroid hormones and neuronal growth factors are two interacting systemic factors that mediate the environment's influence on the brain's structure and function. In order to further elucidate their role and relationship in the effects of early stressful experience and isolated rearing (IR), this study measured blood corticosterone titres and relative adrenal weights and assessed nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) concentrations in brain regions of both hemispheres of young adult Mongolian gerbils injected on postnatal day 14 with a single high dose of methamphetamine (MA) or saline and raised after weaning either in an enriched or an impoverished environment. Irrespective of MA challenge, IR decreased corticosterone titres to about half, but increased relative adrenal weights. BDNF concentrations were decreased by IR in saline-injected animals in the left prefrontal and parietal cortices and right entorhinal and hippocampal cortices, and in the subcortical regions of both hemispheres. NGF concentrations were unaltered by IR in saline-injected animals, but increased in MA challenged animals in the entorhinal/hippocampal cortices and subcortical areas of both hemispheres. MA application induced shifts of the lateral asymmetry in NGF contents in prefrontal and entorhinal cortices. The results suggest that an early pharmacological traumatization can set a switch for further brain development, and that growth factor concentrations might possibly be influenced by peripheral stress hormones.
Hippocampal cell proliferation is strongly increased and synaptic turnover decreased after rearing under social and physical deprivation in gerbils ( Meriones unguiculatus ). We examined if a similar epigenetic effect of rearing environment on adult neuroplastic responses can be found in mice ( Mus musculus ). We examined synaptic turnover rates in the dentate gyrus, CA3, CA1, subiculum, and entorhinal cortex. No direct effects of deprived rearing on rates of synaptic turnover were found in any of the studied regions. However, adult wheel running had the effect of leveling layer-specific differences in synaptic remodeling in the dentate gyrus, CA3, and CA1, but not in the entorhinal cortex and subiculum of animals of both rearing treatments. Epigenetic effects during juvenile development affected adult neural plasticity in mice, but seemed to be less pronounced than in gerbils.
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