Extracellular ATP can be a danger signal, but its role in striatal circuits afflicted in Parkinson's disease (PD) is unclear and was now investigated. ATP was particularly released at high stimulation intensities from purified striatal nerve terminals of mice, which were endowed with different ATP-P2 receptors (P2R), although P2R antagonists did not alter corticostriatal transmission or plasticity. Instead, ATP...
Background: Extracellular vesicles (EVs) carry bioactive molecules associated with various biological processes, including miRNAs. In both Huntington’s disease (HD) models and human samples, altered expression of miRNAs involved in synapse regulation was reported. Recently, the use of EV cargo to reverse phenotypic alterations in disease models with synaptopathy as the end result of the pathophysiological casca...
Despite the characteristic etiologies and phenotypes, different brain disorders rely on common pathogenic events. Glutamate-induced neurotoxicity is a pathogenic event shared by different brain disorders. Another event occurring in different brain pathological conditions is the increase of the extracellular ATP levels, which is now recognized as a danger and harmful signal in the brain, as heralded by the abili...
ATP is released in an activity-dependent manner from different cell types in the brain, fulfilling different roles as a neurotransmitter, neuromodulator, in astrocyte-to-neuron communication, propagating astrocytic responses and formatting microglia responses. This involves the activation of different ATP P2 receptors (P2R) as well as adenosine receptors upon extracellular ATP catabolism by ecto-nucleotidases. ...
Adenosine neuromodulation depends on a balanced activation of inhibitory A1 (A1R) and facilitatory A2A receptors (A2AR). Both A1R and A2AR modulate hippocampal glutamate release and NMDA-dependent long-term potentiation (LTP) but ageing affects the density of both A1R and A2AR. We tested the effects of selective A1R and A2AR antagonists in the modulation of synaptic transmission and plasticity in rat hippocampa...
Adenosine neuromodulation depends on a balanced activation of inhibitory A₁ (A₁R) and facilitatory A(₂A) receptors (A(₂A) R). Both A₁ R and A(₂A) R modulate hippocampal glutamate release and NMDA-dependent long-term potentiation (LTP) but ageing affects the density of both A₁ R and A(₂A) R. We tested the effects of selective A₁ R and A(2A) R antagonists in the modulation of synaptic transmission and plasticity ...
Different presynaptic neuromodulation systems have been explored as possible targets to manage neurodegenerative diseases. However, most studies used young adult animals whereas neurodegenerative diseases are prevalent in the elderly. Thus, we now explored by Western blot analysis how the density of different presynaptic markers and receptors changes with aging in rat hippocampal synaptosomes (purified nerve te...
In many brain regions, Ca2+ influx through presynaptic P2X receptors influences GABA release from interneurones. In patch-clamp recordings of Purkinje cells (PCs) in rat cerebellar slices, broad spectrum P2 receptor antagonists, PPADS (30 [mu]M) or suramin (12 [mu]M), result in a decreased amplitude and increased failure rate of minimal evoked GABAergic synaptic currents from basket cells. The effect is mimicke...
Adenosine is a neuromodulator acting through inhibitory A1 receptors (A1Rs) and facilitatory A2ARs. Since A2AR antagonists attenuate memory deficits in aged animals and memory deficits might involve a decreased cholinergic function, we investigated how aging affects the density and function of adenosine receptors in rat hippocampal cholinergic terminals. In young adult (2 months) rats, 64 and 36% of cholinergic...
Adenosine and dopamine are two important modulators of glutamatergic neurotransmission in the striatum. However, conflicting reports exist about the role of adenosine and adenosine receptors in the modulation of striatal dopamine release. It has been previously suggested that adenosine A1 receptors localized in glutamatergic nerve terminals indirectly modulate dopamine release, by their ability to modulate glut...