Astrocyte pathology in the prefrontal cortex impairs the cognitive function of rats

Interest in astroglial cells is rising due to recent findings supporting dynamic neuron-astrocyte interactions. There is increasing evidence of astrocytic dysfunction in several brain disorders such as depression, schizophrenia or bipolar disorder; importantly these pathologies are characterized by the involvement of the prefrontal cortex and by significant cognitive impairments. Here, to model astrocyte pathology, we injected animals with the astrocyte specific toxin L-a-aminoadipate (L-AA) in the medial prefrontal cortex (mPFC); a behavioral and structural characterization two and six days after the injection was performed. Behavioral data shows that the astrocyte pathology in the mPFC affects the attentional set-shifting, the working memory and the reversal learning functions. Histological analysis of brain sections of the L-AA-injected animals revealed a pronounced loss of astrocytes in the targeted region. Interestingly, analysis of neurons in the lesion sites showed a progressive neuronal loss that was accompanied with dendritic atrophy in the surviving neurons. These results suggest that the L-AA-induced astrocytic loss in the mPFC triggers subsequent neuronal damage leading to cognitive impairment in tasks depending on the integrity of this brain region. These findings are of relevance to better understand the pathophysiological mechanisms underlying disorders that involve astrocytic loss/dysfunction in the PFC.This work was supported by the Marie Curie Fellowship FP7-PEOPLE-2010-IEF 273936, BIAL Foundation Grants 138/2008 and 61/2010, FEDER funds through Operational program for competitiveness factors-COMPETE -, ON2 Programa Operacional Regional do Norte (ON.2-O Novo Norte), QREN/FEDER, and by national funds through FCT-Foundation for Science and Technology-project (PTDC/SAU-NSC/118194/2010) and fellowships (SFRH/BPD/66151/2009 and SFRH/BD/89714/2012)

Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders

There is a long-standing paradox that N-methyl-D-aspartate receptors (NMDARs) can both promote neuronal health and kill neurons. Recent studies show that NMDAR-induced responses depend on the receptor location: stimulation of synaptic NMDARs, acting primarily through nuclear Ca(2+) signaling, leads to the build-up of a neuroprotective ‘shield’, whereas stimulation of extrasynaptic NMDARs promotes cell death. These differences result from the activation of distinct genomic programmes and opposing actions on intracellular signalling pathways. Perturbations in the balance between synaptic and extrasynaptic NMDAR activity contribute to neuronal dysfunction in acute ischaemia and Huntington’s disease and could be a common theme in the aetiology of neurodegenerative diseases. Neuroprotective therapies should aim to both enhance the effect of synaptic activity and disrupt extrasynaptic NMDAR-dependent death signalling

A family of spatial biodiversity measures based on graphs

While much research in ecology has focused on spatially explicit modelling as well as on measures of biodiversity, the concept of spatial (or local) biodiversity has been discussed very little. This paper generalises existing measures of spatial biodiversity and introduces a family of spatial biodiversity measures by flexibly defining the notion of the individuals’ neighbourhood within the framework of graphs associated to a spatial point pattern. We consider two non-independent aspects of spatial biodiversity, scattering, i.e. the spatial arrangement of the individuals in the study area and exposure, the local diversity in an individual’s neighbourhood. A simulation study reveals that measures based on the most commonly used neigh-bourhood defined by the geometric graph do not distinguish well between scattering and exposure. This problem is much less pronounced when other graphs are used. In an analysis of the spatial diversity in a rainforest, the results based on the geometric graph have been shown to spuriously indicate a decrease in spatial biodiversity when no such trend was detected by the other types of neighbourhoods. We also show that the choice neighbourhood markedly impacts on the classification of species according to how strongly and in what way different species spatially structure species diversity. Clearly, in an analysis of spatial or local diversity an appropriate choice of local neighbourhood is crucial in particular in terms of the biological interpretation of the results. Due to its general definition, the approach discussed here offers the necessary flexibility that allows suitable and varying neighbourhood structures to be chosen.PostprintPeer reviewe