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The Management of Treatment-Resistant Depression
Published in Dr. Ather Muneer, Mood Disorders, 2018
The regulation of the glutamate “tripartite” synapse involves presynaptic and postsynaptic neurons and glia. Multiple different receptors regulate glutamate levels as well as the transmission of downstream effects. The following are key targets involved in determining glutamate levels and effects: excitatory amino acid transporters (EAATs), postsynaptic density proteins, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, N-methyl-D-aspartate (NMDA) receptors, kainate (KA) receptors and cognate metabotropic glutamate (mGlu) receptors. Further, modulations of these receptors have been implicated in preclinical models of mood disorders. Therefore, pharmaceutical manipulation of these targets is currently being investigated for TRD.
Hindbrain Astrocyte Glucodetectors and Counterregulation
Published in Ruth B.S. Harris, Appetite and Food Intake, 2017
Richard C. Rogers, David H. McDougal, Gerlinda E. Hermann
Astrocytes are the most abundant cells within the CNS. A single astrocyte may contact tens to hundreds of thousands of synapses and, along with presynaptic terminals and postsynaptic neurons, will form what has been termed the “tripartite synapse” (Araque et al. 1999, Bushong et al. 2002, Halassa et al. 2007, Halassa and Haydon 2010, Perea, Navarrete, and Araque 2009) in which presynaptic terminals and synaptic efficacy as well as the postsynaptic responsiveness to afferent input and neuronal excitability are regulated by astrocytes. Astrocytes, themselves, are subject to afferent synaptic input from neurons, completing the contemporary view of neural–glial interaction (McDougal, Hermann, and Rogers 2011).
Neuroplasticity and rehabilitation therapy
Published in Mark J. Ashley, David A. Hovda, Traumatic Brain Injury, 2017
Recent research by Fellin, Pascual, and Haydon8 has demonstrated the active role of the glial astrocyte in the coordination of the synaptic processes. Although the details of the exact role of this interaction have not been clarified, there is evidence of a feed-forward as well as a feedback modulation of the activity at the “tripartite” synapse (Figure 4.5).
Targeting metabotropic glutamate receptors for rapid-acting antidepressant drug discovery
Published in Expert Opinion on Drug Discovery, 2021
In conclusion, although further studies are required to shed more light on the role of glutamate transmission in depression, accumulating evidence on the therapeutic potential of drugs targeting the tripartite synapse gives hope for a new class of rapid-acting glutamatergic drugs [21]. This is particularly relevant because the treatment of depression is still largely dominated by monoaminergic drugs, especially SSRIs, which are derived from drugs developed more than 50 years ago, take weeks to months to produce a therapeutic response and are only moderately effective, leaving more than one-third of depressed individuals resistant to treatment. Regarding specifically mGlu receptors, the recent advances of chemical synthesis will hopefully provide selective compounds allowing not only the modulation of single subtypes instead of the entire class, but putatively also of selective splice variants, the role, and localization of which are still largely unknown. This would hopefully provide new molecules with better pharmacological and safety profiles, which could improve the quality of life of patients suffering from depression, and still enjoying little benefit from the therapy available to date.
The roles of astrocyte in the brain pathologies following ischemic stroke
Published in Brain Injury, 2019
Linlin Sun, Yixuan Zhang, E Liu, Qingyi Ma, Manaenko Anatol, Hongbin Han, Junhao Yan
The astrocytes can regulate the ion concentration in extracellular space (ECS) to maintain the homeostasis in brain. There are various potassium channels on glial cells, but Kir4.1 plays a leading role in establishment and maintenance of astrocyte membrane potential (11). The astrocytes can rapidly remove the K+ in ECS released from neurons following nervous impulse. In addition, the astrocytes can also absorb the glutamate released during neurotransmission and convert it to glutamine to eliminate glutamate toxicity (12,13). Glutamate plays a pivotal role in regulating synaptic activity (14–16) and activates presynaptic NMDA receptors and promotes excitatory connections between neurons (17,18). Furthermore, a single astrocyte may contact with thousands of synapses, the calcium elevation in astrocyte and subsequent glutamate release will lead to simultaneous excitation of neuron clusters, which indicates that glial transmission might contribute to the neuron synchronization (19). The ‘tripartite synapse’ provides two-way communication between neurons and astrocytes, besides the information flow between presynaptic and postsynaptic neurons, astrocytes can also exchange the information with synaptic neurons and respond to the synaptic activity (20). Therefore, the astrocytes can not only regulate neuronal excitability and synaptic transmission but also promote brain function through coordinating the activities between neurons and glia (21). Moreover, astrocytes can provide linkages between neurons and blood vessels to form neurovascular couplings, which allow astrocytes to be a major mediator for local blood flow in response to neuronal activity (22–24).
A high-fat diet during pregnancy impairs memory acquisition and increases leptin receptor expression in the hippocampus of rat offspring
Published in Nutritional Neuroscience, 2022
Nadia Yanet Cortés-Álvarez, César Rubén Vuelvas-Olmos, María Fernanda Pinto-González, Jorge Guzmán-Muñiz, Oscar Gonzalez-Perez, Norma Angélica Moy-López
Leptin mediates astrocyte morphology, functions, and metabolic responses via Ob-R signaling [53,65,66]. Some reports have suggested the possibility that astrocytic leptin receptors might compete with neuronal Ob-Rs and interfere with neural leptin signaling [15,53,54]. The activation of astrocyte Ob-R may trigger the release of gliotransmitters and neurotransmitters, which can induce a tripartite synapse, influencing neural signaling and cognitive processes [67,68].