Density of dopaminergic fibres in the prefrontal cortex of gerbils is sensitive to aging

Brummelte S, Teuchert-Noodt G. Density of dopaminergic fibres in the prefrontal cortex of gerbils is sensitive to aging. Behavioral and Brain Functions. 2007;3(1): 14.Mesencephalic dopamine (DA) projections are essential for cognitive and behavioral functions and believed to play a critical role during development and aging. The dopaminergic afferents of the rodent prefrontal cortex (PFC) show an extremely prolonged maturation which is very sensitive to epigenetic challenges. However, less is known about the long-term maturation and aging of these DA axons. Therefore, immunohistochemically stained DA fibres were quantitatively examined in the PFC of the Mongolian gerbil (Meriones unguiculatus) ranging from 6 to 24 months of age. Results show a decrease in DA fibre densities in the superficial layers of the PFC in 24 month old animals compared to 6 and 12 months

Influence of methylphenidate on brain development – an update of recent animal experiments

Methylphenidate (MPH) is the most commonly used drug to treat attention deficit/hyperactivity disorder (ADHD) in children effectively and safely. In spite of its widespread application throughout one of the most plastic and sensitive phases of brain development, very little is known to date about its long-term effects on brain structure and function. Hence, this short review updates the influence of MPH on brain development, since recent human and animal studies suggest that MPH alters the dopaminergic system with long-term effects beyond the termination of treatment. Animal studies imply that the effects of MPH may depend on the neural responder system: Whereas structural and functional parameters are improved by MPH in animals with psychomotor impairments, they remain unaltered or get worse in healthy controls. While recent behavioural studies do not fully support such a differential effect of MPH in ADHD, the animal studies certainly prompt for further investigation of this issue. Furthermore, the abuse of MPH, when (rarely) intravenously applied, may even impair the maturation of dopaminergic fibres in subcortical brain areas. This argues for careful clinical assessment and diagnostics of ADHD symptomatology not only in conjunction with the prescription of MPH. Hence, one should be assured that MPH is only given to children with clear ADHD symptomatology leading to psychosocial impairment. The animal data suggest that under these conditions MPH is supportive for brain development and the related behaviour in children with ADHD

Synaptic Remodeling in the Dentate Gyrus, CA3, CA1, Subiculum, and Entorhinal Cortex of Mice: Effects of Deprived Rearing and Voluntary Running

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

Long-term effects of a single adult methamphetamine challenge: Minor impact on dopamine fibre density in limbic brain areas of gerbils

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

Synapse Plasticity in Motor, Sensory, and Limbo-Prefrontal Cortex Areas as Measured by Degrading Axon Terminals in an Environment Model of Gerbils (Meriones unguiculatus)

Still little is known about naturally occurring synaptogenesis in the adult neocortex and related impacts of epigenetic influences. We therefore investigated (pre)synaptic plasticity in various cortices of adult rodents, visualized by secondary lysosome accumulations (LA) in remodeling axon terminals. Twenty-two male gerbils from either enriched (ER) or impoverished rearing (IR) were used for quantification of silver-stained LA. ER-animals showed rather low LA densities in most primary fields, whereas barrel and secondary/associative cortices exhibited higher densities and layer-specific differences. In IR-animals, these differences were evened out or even inverted. Basic plastic capacities might be linked with remodeling of local intrinsic circuits in the context of cortical map adaptation in both IR- and ER-animals. Frequently described disturbances due to IR in multiple corticocortical and extracortical afferent systems, including the mesocortical dopamine projection, might have led to maladaptations in the plastic capacities of prefronto-limbic areas, as indicated by different LA densities in IR- compared with ER-animals

Environmental enrichment has no effect on the development of dopaminergic and GABAergic fibers during methylphenidate treatment of early traumatized gerbils

It is widely believed, that environmental factors play a crucial role in the etiology and outcome of psychiatric diseases such as Attention-Deficit/Hyperactivity Disorder (ADHD). A former study from our laboratory has shown that both methylphenidate (MP) and handling have a positive effect on the dopaminergic fiber density in the prefrontal cortex (PFC) of early traumatized gerbils (Meriones unguiculatus). The current study was performed to investigate if enriched environment during MP application has an additional influence on the dopaminergic and GABAergic fiber densities in the PFC and amygdala in this animal model

Postnatal development of dopamine innervation in the amygdala and the entorhinal cortex of the gerbil (Meriones unguiculatus)

Brummelte S, Teuchert-Noodt G. Postnatal development of dopamine innervation in the amygdala and the entorhinal cortex of the gerbil (Meriones unguiculatus). BRAIN RESEARCH. 2006;1125(1):9-16.Dopamine (DA) projections from the mesencephalon are believed to play a critical role during development and are essential for cognitive and behavioral functions. Since the postnatal maturation patterns of these projections differ substantially between various brain regions, cortical, limbic or subcortical areas might exhibit varying vulnerabilities concerning developmental disorders. The dopaminergic afferents of the rodent prefrontal cortex show an extremely prolonged maturation which is very sensitive to epigenetic challenges. However, less is known about the development of the DA innervation of caudal limbic areas. Therefore, immunohistochemically stained DA fibers were quantitatively examined in the basolateral (BLA) and central amygdaloid nucleus (CE) and the ventrolateral entorhinal cortex (EC) of the Mongolian gerbil (Meriones unguiculatus). Animals of different ages, ranging from juvenile [postnatal day (PD) 14, 20, 30)] to adolescent (PD70), adult (6, 18 months) and aged (24 months), were analyzed. Results show a significant increase of fibers between PD14 and PD20 in the BLA and lateral part of the CE, with a trend for a subsequent decline in fiber densities until PD30. The EC and medial part of the CE showed no developmental changes. Interestingly, none of the investigated areas showed significant reductions of DA fibers during aging. (c) 2006 Elsevier B.V. All rights reserved

A novel pharmacological concept in an animal model of psychosis

Dawirs RR, Teuchert-Noodt G. A novel pharmacological concept in an animal model of psychosis. In: Acta Psychiatrica Scandinavica. ACTA PSYCHIATRICA SCANDINAVICA. Vol 104. MUNKSGAARD INT PUBL LTD; 2001: 10-17.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: 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

Naturally occurring synapse degradation in the developing cerebellum of the mallard (Anas Platyrhynchos) and the Peking duck (Forma Domestica).

Teuchert-Noodt G, Dawirs RR. Naturally occurring synapse degradation in the developing cerebellum of the mallard (Anas Platyrhynchos) and the Peking duck (Forma Domestica). J Hirnforsch. 1996;37(4):547-560.In order to analyze remodelling of junctions as component of adaptive mechanism in the developing avian cerebellum, a silver-staining technique was applied which is highly sensitive towards the detection of lysosomal aggregations (LA) in degrading synapses. LA was quantified in ducks at incubation ages from day 21 to 28 and from hatching up to 32 days. In the mallard, LA increased gradually throughout the whole investigation period, while in the Peking duck LA showed a dramatic increase in the perihatching period followed by the beginning of a decline at about 3 weeks of age. In both species LA occurred initially in the superficial molecular layer prehatching followed by a succession of degradative events down to the granular layer. LA dynamics thus coincide with the outside-in proliferation and differentiation of granule cells during advanced cortical histogenesis. Light microscopy of Epon sections impregnated with silver indicated that granule and Purkinje cell contacts were the center of LA dynamics. Electron microscopy confirmed that synapse degradation occurred predominantly with presynaptic elements of climbing, parallel and mossy afferents. As illustrated by the structural dynamics, maturation of cerebellar circuitry passes through a period of unbalanced synaptogenesis posthatching. Remarkably, the ongoing "critical period" of synaptogenesis in the mallard provides the opportunity for more differentiated behavioral pattern formation in the wild as compared to the domestic duckling

Postnatal rearing conditions influence ontogeny of adult dopamine transporter (DAT) immunoreactivity of the striatum in gerbils

Lehmann K, Teuchert-Noodt G, Dawirs RR. Postnatal rearing conditions influence ontogeny of adult dopamine transporter (DAT) immunoreactivity of the striatum in gerbils. JOURNAL OF NEURAL TRANSMISSION. 2002;109(9):1129-1137.In the present study, the influence of postnatal rearing conditions on the structural maturation of the striatum of adult male gerbils (Meriones unguiculatus) was investigated. For that purpose, animals were bred and reared either grouped in an object-filled environment (EC) or isolated under restricted environmental conditions (IC). At the age of postnatal day 90, dopamine fibers were stained immunocytochemically using an antibody against the dopamine transporter (DAT). Innervation density was determined along the entire rostrocaudal axis of the ventromedial and dorsolateral part of the striatum. As a result, restricted rearing produced a significant restraint of the maturation of striatal dopamine (DA) innervation, leading to adult fiber densities which were approximately 9% below those in semi-naturally reared gerbils. Results are discussed with structural and functional alterations observed in the brain of IC animals