Drug Abuse, Brain Calcification and Glutamate-Induced Neurodegeneration

The L-type voltage-gated calcium channel modulates microglial pro-inflammatory activity

“…The vulnerability of the CNS to excitotoxic insults and hypoxia-ischemia differs according to brain areas (Rodríguez et al, 2009b). The microglial expression of the L-type VGCC described here may contribute to explaining this differential vulnerability.…”

Targeting Microglial KATPChannels to Treat Neurodegenerative Diseases: A Mitochondrial Issue

“…In this situation, three main compensatory responses are activated to avoid glutamate-induced damage [21]. Thus, the direct activation of the retaliatory systems, based on a coordinated increase of GABA, taurine, and adenosine signaling, will reduce glutamate receptor activation [22, 23], and the rapid adaptation of calcium homeostasis with the neuronal and astroglial formation of calcium precipitates will reduce the increased calcium signaling associated with glutamate [3, 24], and the reduction of glutaminase activity of the astrocyte-neuron glutamate/glutamine cycle will reduce glutamate level in the presynaptic neuron and synaptic glutamate activation [25].…”

“…Such a chronic excitotoxic process can be triggered by a dysfunction of glutamate synapses, due to an anomaly at the presynaptic, postsynaptic, or astroglial levels [21]. The contribution of excitotoxicity to the neurodegenerative process can be reproduced by the microinjection of low doses of glutamate agonist into the rodent brain.…”

Microglia, Calcification and Neurodegenerative Diseases

“…A return to basal activity requires a considerable expenditure of energy to bring Ca 2+ back to initial levels. Any failure in these multiple, coordinated steps will alter neuronal signalling and interfere with neuronal network functions (Rodriguez et al, 2009b). Reduction of [Ca 2+ ] i involves a high mitochondrial intake of Ca 2+ that may lead to loss of the mitochondrial membrane potential and the production of reactive oxygen species, thereby decreasing cellular respiratory capacity and ATP formation from ADP and Pi (Chan et al, 2007a).…”

“…Over time, these defenses are developed to act at any time during an excitotoxic event, involve different cellular types such as neurons, astrocytes and microglia, and deal with the cellular and molecular mechanisms of glutamatergic neurotransmission. These mechanisms include defenses that: a) decrease neuronal excitability, b) decrease glutamate accumulation in the synapse, c) limit Ca 2+ mobilization in the postsynaptic neuron and protect against calcium-dependent degenerative effects, and d) enhance neuronal energy (Rodriguez et al, 2009b, Sapolsky, 2001. If the compensatory mechanisms are not sufficiently effective, the initial acute neuronal injury due to an increase in [Ca 2+ ] i leads, with time, to a chronic lesion.…”