Search

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.anbehav.2008.05.022 Byline: Gaia Dell'Ariccia, Giacomo Dell'Omo, David P. Wolfer, Hans-Peter Lipp Abstract: The effects of aggregation in navigating animals have generated growing interest in field and theoretical studies. The few studies on the effects of group flying on the performance of homing pigeons, Columba livia, have led to controversial conclusions, chiefly because of the lack of appropriate technology to follow pigeons during their entire homeward flight. Therefore, we used GPS data loggers on six highly trained pigeons from a familiar release site first by releasing them six times individually, then six times as a group from the same site, and, finally, again six times individually. Flight data showed that the homing performance of the birds flying as a flock was significantly better than that of the birds released individually. When flying in a flock, pigeons showed no resting episodes, shorter homing times, higher speed, and almost no circling around the start zone in comparison to individual flights. Moreover, flock-flying pigeons took a nearly direct, 'beeline' route to the loft, whereas individually flying birds preferred to follow roads and other longitudinal landmarks leading towards the loft, even when it caused a detour. Our results show that group cohesion facilitates a shift towards more efficient homing strategies: individuals prefer navigating by familiar landmarks, while flocks show a compass orientation. Author Affiliation: (a) Institute of Anatomy, University of Zurich, Switzerland (a ) Institute of Human Movement Sciences and Sport, ETH Zurich, Switzerland Article History: Received 10 October 2007; Revised 20 November 2007; Accepted 18 May 2008 Article Note: (miscellaneous) MS. number: 9555R

Functional analysis of the mouse beta-amyloid precursor protein (beta-APP) gene by incorporating a cassette consisting of a putative transcription terminating sequence and a neomycin resistance gene into exon 2 reveals that the brain and other tissues in mice that are homozygous to the cassette incorporation contain beta-APP-specific RNA at a concentration 5- to 10-fold less than that in wild type protein. The levels of the shortened beta-APP-specific protein were low in the brain. The mice display damaged exploratory behavior and spatial learning characteristics with a high level of corpus callosum agenesis.

Abstract: Mitochondrial dysfunction and oxidative stress have been implicated in Parkinson disease (PD). In addition, genetic evidence points to an important role of protein misfolding, aggregation, and failure in the proteasomal degradation of specific neuronal proteins in the pathogenesis of PD. The chaperone heat-shock protein 70 (Hsp70) reduces protein misfolding and aggregation and protects cells against a variety of adverse conditions, including oxidative stress. Moreover, Hsp70 exerts antiapoptotic activity by blocking the function of several key proapoptotic factors. Recently, Hsp70 was shown to inhibit α-synuclein toxicity in a Drosophila model of inherited PD. Here we tested the potential of Hsp70 (approved gene symbol HSPA1A) for gene therapy in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of idiopathic PD. We show that Hsp70 gene transfer to dopamine neurons by a recombinant adeno-associated virus significantly protects the mouse dopaminergic system against MPTP-induced dopamine neuron loss and the associated decline in striatal dopamine levels and tyrosine hydroxylase-positive fibers. Hsp70 reduced MPTP-induced apoptosis in the substantia nigra, and unilateral protection of the dopaminergic system by Hsp70 was associated with increased amphetamine-induced turning toward the uninjected side. Collectively, these results suggest that increasing chaperone activity may be beneficial for the treatment of idiopathic PD. [Copyright &y& Elsevier]

Presents simple breeding strategies to test for flanking gene effects that are compatible with the recommendations of the Banbury Conference on Genetic Background in Mice and with common practices of creating and maintaining mouse knockout lines. Interactions with genetic background and environment; Inadequacies of the Banbury Conference recommendations; Available strategies to solve the flanking gene problem; Details of the breeding strategies.

Summary: Early experiences shape brain function and behavior and, consequently, vulnerability to psychopathology at adulthood. Here we exploited the mouse communal nest (CN) paradigm in order to investigate the effect of the early social environment on the emergence of endophenotypes of depression and on antidepressant efficacy at adulthood. CN, which consists in a single nest where three mothers keep their pups together and share care-giving behavior until weaning, is characterized by high levels of maternal behavior and peer interactions, thus representing an highly stimulating environment. Our results show that, when compared to mice reared in standard laboratory conditions (SN), adult CN mice exhibited greater sucrose preference on the first days of the test, displayed reduced anhedonia during social stress and had lower corticosterone levels after acute and prolonged social stress. Furthermore, in line with previous work, CN displayed longer immobility than SN mice in the forced swim test. Here we show that such behavioral response is differently affected by antidepressants according to early experiences. A 3-week fluoxetine treatment affected only SN mice, leading to an increase of immobility duration up to the levels showed by CN mice, while acute fluoxetine administration decreased immobility duration in both groups. These results show that being reared in a CN profoundly changes developmental trajectories, reducing the adult display of endophenotypes of depression and modifying response to antidepressants. The present findings suggest that early experiences represent one of those factors to be taken into account to identify the appropriate individual pharmacological strategy to treat depression in patients. [Copyright &y& Elsevier]

Abstract: Strong age-related declines in conjunction with comparatively easy experimental manipulations of adult hippocampal neurogenesis have generated considerable public and scientific interest in the prospect of “new neurons for old brains”. Only few studies addressed the time course of the natural changes, which are the substrate for interventions that may realize this prospect. We provide a monthly or bimonthly account of cell proliferation, neurogenesis and cell death during the first 9 months of the life of C57Bl/6J mice. Ki67- and DCX-positive cell numbers declined exponentially without an intermittent plateau (∼40% per month). Cell death in relation to cell proliferation was lowest at 1 month, increased at 2 months to remain constant until 4 months, and decreased again at 5 months to remain stable until 9 months. Granule cell number did not change with age. Our results suggest that manipulations of proliferation and neurogenesis may, at any time, interact with strong natural changes of these processes. Mediators of their age-related decline may be studied over periods much shorter than those typically used. [Copyright &y& Elsevier]

An abstract of the article "Viral Vector-Mediated Chaperone Gene Therapy in a Mouse Model of Sporadic Parkinson Disease," by Zhizhong Dong and colleagues is presented.

Objective: Imatinib mesylate is a novel tyrosine kinase inhibitor used for the treatment of Philadelphia chromosome positive (Ph+) leukemia and other malignancies. In previous studies, we found significant telomere shortening in Ph+ cells from patients with chronic myeloid leukemia (CML). Interestingly, imatinib treatment was found to lead to a normalization of previously shortened telomere length in CML patients. Based on recent reports demonstrating that c-ABL phosphorylates hTERT and thereby inhibits hTERT activity, a direct effect of imatinib on hTERT activity leading to telomere elongation in BCR-ABL-positive cells has been proposed by others. Such an effect could be of potential importance for telomere maintenance in Ph+ cells by facilitating clonal selection and progression of the disease to blast crisis. Methods: We investigated the impact of imatinib on telomere length and telomerase activity of the interleukin-3 (IL-3)-dependent murine pro-B cell line BaF3 and the BCR-ABL-positive, IL-3-independent transfectant BaF3p185 in vitro. Results: When BaF3 and BaF3p185 cells were treated with imatinib (the latter being rescued with IL-3), no effect on either telomerase activity or telomere length was observed. These findings can be explained by the cytoplasmatic localization of BCR-ABL found in BaF3p185 as compared to the nuclear localization of telomerase (and c-ABL). Conclusion: As opposed to recent reports for c-ABL, we do not see evidence for a functional interaction between BCR-ABL and hTERT in this model system arguing against imatinib-mediated upregulation of hTERT as a crucial factor for clonal selection and disease progression of CML. [Copyright &y& Elsevier]

: BackgroundAccording to the neurotrophin hypothesis of depression, decreased activity of brain-derived neurotrophic factor (BDNF) contributes to behavioral and plasticity-related alterations in depressed patients. We investigated the hypothesis that mice with a forebrain-specific knockout of the trkB receptor, the main mediator of BDNF signaling, represent a genetic animal model for depression.: MethodsUsing the CRE-loxP system, we bred trkBCaMKII-CRE mice with a trkB-receptor disruption in the forebrain. We subjected trkB-mutant mice to a battery of behavioral tests, comprising open field, elevated zero maze, emergence test, novel object test, and forced swim. Additionally, we investigated the hypothalamic-pituitary-adrenal (HPA) axis immunohistochemically and by plasma analyses.: ResultstrkBCaMKII-CRE mice showed a stereotyped hyperlocomotion with reduced explorative activity, and impulsive reactions to novel stimuli. The trkB-mutant mice did not exhibit depressionlike behaviors such as increased “despair” in the forced swim test, increased anxiety in the elevated zero maze, or neophobia in the novel object test. Furthermore, no HPA dysregulation was observed under normal and stressful conditions.: ConclusionstrkBCaMKII-CRE mice cannot be regarded as a genetic mouse model of depression. Instead, the behavioral symptoms of trkBCaMKII-CRE mice, comprising hyperlocomotion, stereotyped behaviors, and cognitive impairments, are similar to those postulated for mouse models of attention-deficit disorder. [Copyright &y& Elsevier]