China
Africa
Explore chapters and articles related to this topic
Two-Pore Domain Potassium Channels in Pain and Depression
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
However, the role of 5-HT in depression has been questioned in recent years (Cowen and Browning 2015). To obtain a better understanding of the TREK-1 channel in antidepressant treatment, it is necessary to determine the relationship between TREK-1 and other cells in addition to 5-HT neurons. Hwang et al. reported that TREK-1 formed heterodimeric channels with TWIK-1 in astrocytes. These heterodimers mediated the release of glutamate in astrocytes induced by cannabinoid (Hwang et al. 2014). According to preclinical and clinical trials, glutamatergic system dysfunction has been implicated in the pathophysiology of mood disorders such as bipolar depression and MDD (Henter et al. 2018). Therefore, TREK-1/TWIK-1 heterodimers of astrocytes may be a potential target in the treatment of depression. By generating a Cre-dependent TREK-1 knockdown (Cd-TREK-1 KD) transgenic mouse, Kim et al. found that selectively inhibiting TREK-1 in hippocampal neurons could provide antidepressant effects (Kim et al. 2019). This result implies that Cd-TREK-1 KD mice will be a valuable tool for revealing the antidepressant function of TREK-1 in the brain.
Neurons
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
Neurons can also be classified according to the neurotransmitter they release at their axon terminals. The neuron is described by adding the suffix “ergic” to part of the name of the neurotransmitter. Thus, neurons that release ACh are cholinergic neurons. Similarly, neurons can be glutamatergic, GABAergic, glycinergic, dopaminergic, serotonergic, etc. if they release the respective neurotransmitter concerned (Section 6.1.2.1).
Pharmacological Management of Amyotrophic Lateral Sclerosis
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Shalini Mani, Chahat Kubba, Tanya Sharma, Manisha Singh
In the mammalian neurons, glutamic acid is the key neurotransmitter responsible for excitation in the CNS (Meldrum, 2000). When depolarization occurs, the release of glutamate is observed from the glutamatergic nerve terminals; by crossing the synaptic cleft it acts on postsynaptic target molecules. Following its action, glutamic acid is efficiently removed from the synapse by glutamate uptake systems in glia and nerve terminals (Auger et al., 2000). However, in ALS, elevated concentrations of glutamic acid can gather in the synaptic cleft causing excitotoxic conditions and prolonged depolarization thereafter (Bosch et al., 2006). Riluzole drug acts by blocking the excitotoxic process by targeting various processes such as inhibition of glutamic acid release and inhibition of voltage-dependent sodium channels or voltage-dependent calcium channels on nerve endings and cell bodies. All processes work in synergy to contribute to its powerful neuroprotective action (Doble, 1996). The potential sites of action of riluzole have been depicted in Figure 8.1.
Neural Plasticity in the Ventral Tegmental Area, Aversive Motivation during Drug Withdrawal and Hallucinogenic Therapy
Published in Journal of Psychoactive Drugs, 2023
Hector Vargas-Perez, Taryn Elizabeth Grieder, Derek van der Kooy
The modulation of neuronal plasticity induced by BDNF is closely related to the regulation of the signaling of glutamate, the main excitatory neurotransmitter in the brain (Minichiello 2009). The subtle balance of glutamate transmission is crucial for the healthy functioning of an organism. Overactivation of glutamatergic signaling, called excitotoxicity (Manev et al. 1989), is related to various pathologies, from inflammatory processes and allergies to chronic degenerative diseases, including Alzheimer’s disease, depression, Parkinson’s disease, amyotrophic lateral sclerosis and epilepsy (Ishikawa 2013; Lai, Zhang, and Wang 2013; Lapidus, Soleimani, and Murrough 2013). In this way, the regulation of the glutamate signal is an opportunity for the development of therapies for diseases related to depressive states, and in general for other pathologies related to aberrant glutamatergic signaling.
Change in gene expression levels of GABA, glutamate and neurosteroid pathways due to acoustic trauma in the cochlea
Published in Journal of Neurogenetics, 2021
Meltem Cerrah Gunes, Murat Salih Gunes, Alperen Vural, Fatma Aybuga, Arslan Bayram, Keziban Korkmaz Bayram, Mehmet Ilhan Sahin, Muhammet Ensar Dogan, Sevda Yesim Ozdemir, Yusuf Ozkul
Acoustic trauma causes damage to the peripheral and central auditory system. Glutamate excitotoxicity damages the auditory SGNs causing loss of postsynaptic terminals and cell dysfunction (Kujawa & Liberman, 2015). Excitation generated by glutamatergic neurons is compensated by cortical inhibition (Froemke, 2015). One week after the noise exposure, especially ipsilateral elevation of the number of GABAergic interneurons containing the calcium-binding protein Parvalbumin(PV) was observed and this was thought to be a compensatory mechanism (C. Liu et al., 2018). Neurosteroids take part in the regulation of neuronal function by modulating the expression of GABAA and NMDA receptor subgroups (Compagnone & Mellon, 2000). To elucidate this relationship in glutamate, GABA and neurosteroid pathways in acoustic trauma, we investigated mice exposed to intense noise and examined expressions of related genes in the cochlea.
Multi-targeted drug design strategies for the treatment of schizophrenia
Published in Expert Opinion on Drug Discovery, 2021
Piotr Stępnicki, Magda Kondej, Oliwia Koszła, Justyna Żuk, Agnieszka A. Kaczor
Increasing evidence indicates that the glutamatergic system is involved in the development of schizophrenia. Glutamate is involved in the formation of the memory pathway, which means it has a significant effect on synaptic plasticity and cortical microcircuits [19]. Originally, this hypothesis was based on the assumption that there was a glutamatergic neurotransmission deficit in schizophrenia. For many years, the concept has been modified and developed, involving many glutamate receptors. However, the most important role in this hypothesis is fulfilled by dysfunction of N-methyl-D-aspartate (NMDA) receptor [12]. The NMDA receptor is a glutamate-gated ionotropic receptor that plays an important role in the development of neuronal plasticity. Postmortem examinations show that patients with schizophrenia are characterized by lower density of glutamatergic receptors. The combination of NMDA receptor deficiency and dopaminergic neurotransmission dysfunction can be a simple explanation for most clinical aspects of schizophrenia. Many studies indicate that the activation of D1 and D2 dopamine receptors is responsible for the regulation of NMDA receptor function. In addition, it is suggested that activation of D1 receptor is associated with increased expression of the NMDA receptor NR2B subunit in the prefrontal cortex and affects the subcellular location of NMDA receptors [20].