Age-related alterations in hippocampal spines and deficiencies in spatial memory in mice.

Alterations in neuronal morphology occur in the brain during normal aging, but vary depending on neuronal cell types and brain regions. Such alterations have been related to memory and cognitive impairment. Changes in hippocampal spine densities are thought to represent a morphological correlate of altered brain functions associated with hippocampal-dependent learning and memory. We therefore have analyzed the impact of aging on different hippocampal-dependent learning tasks and on changes in dendritic spines of CA1 hippocampal and dentate gyrus neurons by analyzing adult (6-7 months) and aged (21-22 months) C57/Bl6 mice. We found a significant decrease in spine numbers of basal CA1 dendrites and decreases in spine length of apical dendrites of CA1 and dentate gyrus neurons. Furthermore, aged mice exhibited significant deficits in hippocampus-dependent learning tasks, such as the probe trial of the Morris water maze and T maze learning. Given the fact that there is no neuronal loss in the hippocampus in aged mice (von Bohlen und Halbach and Unsicker [2002] Eur. J. Neurosci. 16:2434-2440), we suggest that the memory and cognitive decline in the context of aging may be accompanied by rather subtle anatomical changes, such as numbers and morphology of dendritic spines.

mPer1 and mPer2 mutant mice show regular spatial and contextual learning in standardized tests for hippocampus-dependent learning.

Learning and memory, like most physiological processes, seem to be under the control of circadian rhythm. The recently cloned mPer1 and mPer2 genes play an important role in the regulation of the circadian rhythm. In this study, we tested mPer1 and mPer2 mutant mice in two different learning and memory paradigms, a water-maze place navigation task and contextual fear conditioning. In both learning tests, the hippocampus is critically involved. None of these learning types were affected by the mutations, suggesting that mPer1 and mPer2 do not play a major role in the regulation of hippocampus-dependent learning and memory.

Learned helplessness: validity and reliability of depressive-like states in mice.

The learned helplessness paradigm is a depression model in which animals are exposed to unpredictable and uncontrollable stress, e.g. electroshocks, and subsequently develop coping deficits for aversive but escapable situations (J.B. Overmier, M.E. Seligman, Effects of inescapable shock upon subsequent escape and avoidance responding, J. Comp. Physiol. Psychol. 63 (1967) 28-33 ). It represents a model with good similarity to the symptoms of depression, construct, and predictive validity in rats. Despite an increased need to investigate emotional, in particular depression-like behaviors in transgenic mice, so far only a few studies have been published using the learned helplessness paradigm. One reason may be the fact that-in contrast to rats (B. Vollmayr, F.A. Henn, Learned helplessness in the rat: improvements in validity and reliability, Brain Res. Brain Res. Protoc. 8 (2001) 1-7)--there is no generally accepted learned helplessness protocol available for mice. This prompted us to develop a reliable helplessness procedure in C57BL/6N mice, to exclude possible artifacts, and to establish a protocol, which yields a consistent fraction of helpless mice following the shock exposure. Furthermore, we validated this protocol pharmacologically using the tricyclic antidepressant imipramine. Here, we present a mouse model with good face and predictive validity that can be used for transgenic, behavioral, and pharmacological studies.

Olfactory bulbectomy in mice induces alterations in exploratory behavior.

The olfactory bulbectomy syndrome is thought to represent a rodent model for psychomotor agitated depression. While this model has been extensively characterized in rats, fewer studies have been conducted with mice. Therefore, the present study aimed at extending the characterization of the OBX-induced behavioral syndrome in mice, using tests like open field, novel object exploration, novel cage and T-maze learning. OBX mice exhibited hyperactivity in a brightly illuminated open field, and also in a novel home cage as well as in the T-maze. Furthermore, OBX mice demonstrated increased exploratory behavior in the novel object test and in the T-maze. The complex alterations described here with respect to locomotion and exploration are robust and can be achieved by relatively simple test procedures. The extended behavioral characterization of the murine OBX model may contribute in particular to the increasing need to test transgenic mice for the presence of depression-like behaviors.

Memory retrieval after contextual fear conditioning induces c-Fos and JunB expression in CA1 hippocampus.

Using specific polyclonal antisera against c-Fos, JunB, c-Jun and JunD, we tried to identify the candidate transcription factors of the immediate early gene family which may contribute to the molecular processes during contextual memory reconsolidation. For that purpose we analyzed the expression of these proteins in the hippocampus after contextual memory retrieval in a mouse model of fear conditioning. A single exposure to a foot shock of 0.8 mA was sufficient to induce robust contextual fear conditioning in C57BI/6N mice. In these mice context dependent memory retrieval evoked a marked induction of c-Fos and JunB, but not of c-Jun and JunD, in pyramidal CA1 neurons of the dorsal hippocampus. In contrast, mice exposed and re-exposed only to the context, without foot shock, did not show behavioral signs of contextual fear conditioning and exhibited significantly less expression of c-Fos and JunB in CA1 neurons. Mice which received a foot shock but were not re-exposed to the context revealed no immediate early gene induction. These results demonstrate that contextual memory retrieval is associated with de novo synthesis of specific members of the Fos/Jun transcription factor family. Therefore we suggest that these genes may contribute to plasticity and reconsolidation accompanying the retrieval process. The specific activation of CA1 neurons during the retrieval of contextual fear associations supports the postulated concept of a mnemonic role of this hippocampal subsector during the retrieval of contextual informations.

Effect of menstrual cycle phase on carbohydrate supplementation during prolonged exercise to fatigue.

The effects of menstrual cycle phase and carbohydrate (CHO) supplementation were investigated during prolonged exercise. Nine healthy, moderately trained women cycled at 70% peak O(2) consumption until exhaustion. Two trials were completed during the follicular (Fol) and luteal (Lut) phases of the menstrual cycle. Subjects consumed 0.6 g CHO. kg body wt(-1). h(-1) (5 ml/kg of a 6% CHO solution every 30 min beginning at min 30 of exercise) or a placebo drink (Pl) during exercise. Time to exhaustion during CHO increased from Pl values (P < 0.05) by 14.4 +/- 8.5 (Fol) and 11.4 +/- 7.1% (Lut); no differences were observed between menstrual cycle phases. CHO attenuated (P < 0.05) the decrease in plasma glucose and insulin and the increase in plasma free fatty acids, tryptophan, epinephrine, and cortisol observed during Pl for both phases. Plasma alanine, glutamine, proline, and isoleucine were lower (P < 0.05) in Lut than in Fol phase. CHO resulted in lower (P < 0.05) plasma tyrosine, valine, leucine, isoleucine, and phenylalanine. These results indicate that the menstrual cycle phase does not alter the effects of CHO supplementation on performance and plasma levels of related substrates during prolonged exercise.

[Glucocorticoids in dental surgery and maxillofacial surgery]. / Glukokortikoide in der chirurgischen Stomatologie und Kiefer-Gesichts-Chirurgie.

Indications for the use of glucocorticoids in surgical stomatology are: 1. emergencies, 2. bullous and allergic diseases of the oral mucosa and therapy-resistant cases of chronic recurrent aphthae, erosive lichen planus and sialoses (for systemic therapy), 3. therapy-resistant temporomandibular complaints and hyperplastic tissue responses and, in combination with an antibiotic, diseases of the maxillary sinus (for local therapy). Preliminary clinical examination, case controls at short intervals, and circadian or alternating prescription will help to reduce undesirable side-effects. In patients receiving sustained glucocorticoid therapy, dental-surgical procedures require special consideration of the change in reactivity.