Concerted Gene Expression of Hippocampal Steroid Receptors during Spatial Learning in Male Wistar Rats: A Correlation Analysis

Adrenal and gonadal steroid receptor activities are significantly involved and interact in the regulation of learning, memory and stress. Thus, a coordinated expression of steroid receptor genes during a learning task can be expected. Although coexpression of steroid receptors in response to behavioral tasks has been reported the correlative connection is unclear. According to the inverted U-shape model of the impact of stress upon learning and memory we hypothesized that glucocorticoid (GR) receptor expression should be correlated to corticosterone levels in a linear or higher order manner. Other cognition modulating steroid receptors like estrogen receptors (ER) should be correlated to GR receptors in a quadratic manner, which describes a parabola and thus a U-shaped connection. Therefore, we performed a correlational meta-analyis of data of a previous study (Meyer and Korz, 2013a) of steroid receptor gene expressions during spatial learning, which provides a sufficient data basis in order to perform such correlational connections. In that study male rats of different ages were trained in a spatial holeboard or remained untrained and the hippocampal gene expression of different steroid receptors as well as serum corticosterone levels were measured. Expressions of mineralocorticoid (MR) and GR receptors were positively and linearly correlated with blood serum corticosterone levels in spatially trained but not in untrained animals. Training induced a cubic (best fit) relationship between mRNA levels of estrogen receptor (ER) and androgen receptor (AR) with MR mRNA. GR gene expression was linearly correlated with MR expression under both conditions. ER m RNA levels were negatively and linearily and MR and GR gene expressions were cubicely correlated with reference memory errors (RME). Due to only three age classes correlations with age could not be performed. The findings support the U-shape theory of steroid receptor interaction, however the cubic fit suggest a more complex situation, which mechanisms may be revealed in further studies.(VLID)511801

Low-Affinity/High-Selectivity Dopamine Transport Inhibition Sufficient to Rescue Cognitive Functions in the Aging Rat

The worldwide increase in cognitive decline, both in aging and with psychiatric disorders, warrants a search for pharmacological treatment. Although dopaminergic treatment approaches represent a major step forward, current dopamine transporter (DAT) inhibitors are not sufficiently specific as they also target other transporters and receptors, thus showing unwanted side effects. Herein, we describe an enantiomerically pure, highly specific DAT inhibitor, S-CE-123, synthetized in our laboratory. Following binding studies to DAT, NET and SERT, GPCR and kinome screening, pharmacokinetics and a basic neurotoxic screen, S-CE-123 was tested for its potential to enhance and/or rescue cognitive functions in young and in aged rats in the non-invasive reward-motivated paradigm of a hole-board test for spatial learning. In addition, an open field study with young rats was carried out. We demonstrated that S-CE-123 is a low-affinity but highly selective dopamine reuptake inhibitor with good bioavailability. S-CE-123 did not induce hyperlocomotion or anxiogenic or stereotypic behaviour in young rats. Our compound improved the performance of aged but not young rats in a reward-motivated task. The well-described impairment of the dopaminergic system in aging may underlie the age-specific effect. We propose S-CE-123 as a possible candidate for developing a tentative therapeutic strategy for age-related cognitive decline and cognitive dysfunction in psychiatric disorders

Social relations and individual coping reactions in a captive group of Central American Agoutis (Dasyprocta punctata)

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Treatment with MPP had an effect on hippocampal relative gene expression of ERα, MR, GR, AR, and BDNF, but not ERβ and aromatase (<i>Cyp 19</i>) encoding genes in a dose-dependent manner with statistically significant lower expression of only the group treated with 7.4 µmol MPP compared to the trained vehicle-treated animals.

<p>Horizontal lines with asterisks indicate statistically significant differences. Numbers in brackets indicate sample sizes. Longer vertical lines indicate the groups against which the other groups were tested. Given are the arithmetic means and the s.e.m.</p

Reinforcement of rat hippocampal LTP by holeboard training

Hippocampal long-term potentiation (LTP) can be dissociated in early-LTP lasting 4–5 h and late-LTP with a duration of more than 8 h, the latter of which requires protein synthesis and heterosynaptic activity during its induction. Previous studies in vivo have shown that early-LTP in the dentate gyrus can protein synthesis-dependently be transformed (reinforced) into late-LTP by the association of arousing novel environmental stimuli. Here we show that consolidation of spatial memory also reinforces early-LTP in the dentate gyrus. Both memory consolidation and LTP-reinforcement depend on protein synthesis. Four groups of animals were trained by five, seven, eight or 10 trials, respectively, to recognize a fixed pattern of baited holes. The last trial was performed 15 min after tetanus. Errors of long-term reference memory during the last trial were significantly decreased only in the eight- and 10-trial experimental groups compared to pseudo-trained animals. In correlation to this learning effect we found a reinforcement of early-LTP only in these experimental groups compared to controls. The data suggest that the synthesis of new proteins required for spatial reference-memory formation also contributes to LTP maintenance in the hippocampal dentate gyrus

Dendritic Spine Plasticity and Cognition

[No abstract available

Treatment with MPP at any concentration had a statistically significant effect on the hippocampal concentrations of corticosterone only between the group treated with 3.7 µmol compared to the groups treated with 1.5 µmol and 7.4 µmol MPP.

<p>Serum concentrations were not different, and no difference between groups was found for testosterone and 17β-estradiol. Horizontal lines with asterisks indicate statistically significant differences. Numbers above columns indicate sample sizes. Longer vertical lines indicate the groups against which the other groups were tested. Given are the arithmetic means and the s.e.m.</p