Mechanisms of astroglial glutamate release and brain ageing
Lead Research Organisation:
University of Warwick
Department Name: School of Life Sciences
Abstract
Republic of Korea (South Korea)
People |
ORCID iD |
| Yuriy Pankratov (Principal Investigator) |
Publications
Lalo U
(2016)
ATP from synaptic terminals and astrocytes regulates NMDA receptors and synaptic plasticity through PSD-95 multi-protein complex.
in Scientific reports
| Description | Brain function depends on the interaction between two cellular circuits: neurons transmitting electrical signals and glial cells which maintain the wellbeing and function of neurons. An impairment of glial function has been implicated to the pathogenesis of many neurological disorders. Recent data, including our work, show that astroglia can modulate synaptic transmission and plasticity via release of gliotransmitters, such as ATP, glutamate and D-Serine. However, the age-related changes in the mechanisms of astrocyte-neuron interaction remained almost unexplored. We studied the impact of physiological and pathological ageing on Ca2+-dependent release of gliotransmitters and astroglial modulation of neocortical synapses. We obtained unique data on quantal synaptic currents in the neocortex of wild-type and AD model mice (line APP/PS1). We observed the considerable decline in the astrocytic Ca2+-signaling towards the old age (12-24 months) and significant decrease in the astrocytic signaling in the APP/PS1 mice. Consistent with changes in the Ca2+-signaling, the release of ATP, glutamate and D-Serine from astrocytes declined in the old age and in the AD model mice. Rather surprisingly, majority of neocortical pyramidal neurons of aged WT and APP/PS1 mice retained large number of functional synapses. However, impairment of glia-derived regulation altered the balance between excitation and inhibition. The significant decline in the quantal size of AMPA and NMDA receptor-mediated synaptic currents contrasted with significant up-regulation of GABAergic currents. We also observed the age- and AD-related deficit in the long-term synaptic plasticity. Importantly, the neocortical LTP could be rescued by additional activation of astrocytic Ca2+-signalling. Furthermore, the negative impact of ageing on the glial signalling and synaptic currents was remedied by environmental enrichment. Combined, our data show that astrocyte-neuron interaction can significantly decline with ageing and thus contribute to the age- and pathology-related cognitive impairment. Also, our results strongly support the importance of gliotransmission for the brain metaplasticity |
| Exploitation Route | The outcome of the proposed research will be new understanding of the role for astroglial cells in brain function and physiology and pathology of ageing. The pharmacological data obtained in the proposed experiments can greatly promote development of novel therapeutic interventions in ageing-related neurological disorders. |
| Sectors | Pharmaceuticals and Medical Biotechnology |
| Description | The fundings have been used in lectures and talks to public during Science Event "A healthy brain for a healthy life " at School of Life Science, University of Warwick |
| First Year Of Impact | 2016 |
| Sector | Healthcare |
| Impact Types | Societal |