China
Africa
Explore chapters and articles related to this topic
Insulin and Brain Reward Systems
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
Brian C. Liu, Qingchen Zhang, Emmanuel N. Pothos
It is perhaps too early to claim a sufficient understanding of the several roles of central insulin in physiology and disease. Nevertheless, in this chapter, we have attempted to focus on the central interactions of insulin and its receptors with dopaminergic neurotransmission and mesolimbic pathways, a system that is apparently coding for the reward value and reward prediction of stimuli like food and drugs of misuse. And the possible impact of such interactions on the phenotype of disorders with signature deficits of dopaminergic neurotransmission like addictive disorders, mood disorders, and Parkinson’s disease. The direct impact of insulin on major regulators of dopamine exocytosis, like the dopamine transporter, as well as the modulation of dopaminergic signaling by cellular and molecular mechanisms that reside with IRs in both neurons and astrocytes provide a good first insight into how central insulin functions and on possible new therapeutic approaches for these disorders that target central IRs.
Exocytosis of Nonclassical Neurotransmitters
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Xiao Su, Vincent R. Mirabella, Kenneth G. Paradiso, Zhiping P. Pang
Brain function relies on the regulated release of chemical substances known as neurotransmitters at specialized junctions between neurons called synapses. Synaptic transmission is mainly mediated by classical neurotransmitters such as glutamate and γ-amino butyric acid (GABA), which normally transduce fast information flow in the brain. This process is further regulated by released neuromodulators including monoamines and neuropeptides. Dysfunctional neurotransmission is a major component of many neurological disorders and neuropsychiatric disorders, which include schizophrenia, depression, bipolar disorders, and eating disorders, as well as neurodevelopmental disorders such as autism spectrum disorders (ASDs). Since the discovery of synapses over 100 years ago, scientists have made major breakthroughs in determining the mechanisms and function of synaptic transmission. While it is impossible to fully comprehend all that we now know about synaptic transmission, we will review many of the fundamental discoveries and our current knowledge on neurotransmitter release. It is indisputable that understanding the mechanism and regulation of neurotransmitter release is a fundamental area of investigation in unraveling how the brain works.
Mechanistic Aspects of Neurodegeneration in Alzheimer’s Disease and the Role of Phytochemicals as Restorative Agents
Published in Atanu Bhattacharjee, Akula Ramakrishna, Magisetty Obulesu, Phytomedicine and Alzheimer’s Disease, 2020
Anindita Kundu, Vivekananda Mandal, Sujata Wangkheirakpam, Subhash C. Mandal
Neurotransmitters, also known as endogenous chemical messengers, enable neurotransmission of signals across the chemical synapses. To maintain the homeostatic balance of neural circuits, diverse sets of inhibitory interneurons regulate the activity of excitatory neurons in the CNS. Impaired co-activation of excitatory and inhibitory neurons, such as substantial loss of gamma amino butyric acid (GABA)-ergic interneurons, dysfunction of interneurons due to loss of their afferent excitatory input, changes in their receptors, and an imbalance of the different neurotransmitters, like glutamate, acetylcholine, dopamine, and serotonin, have been proposed in many neurobiological disorders like AD. AD is a neurodegenerative disorder which is characterized by memory loss, and behavioral and psychological symptoms of dementia (Southwell et al., 2014). It is hypothesized that altered reuptake of neurotransmitters by vesicular glutamate transporters (VGLUTs), excitatory amino acid transporters (EAATs), the vesicular acetylcholine transporter (VAChT), the serotonin reuptake transporter (SERT), or the dopamine reuptake transporter (DAT), are involved in the neurotransmission imbalance in AD. Compared with control subjects, the protein and mRNA levels of VGLUTs, EAAT1–3, VAChT, and SERT are reduced significantly in AD subjects; playing a contributory role to the recognized cholinergic deficiency, alteration in glutamatergic recycling and reduced SERT levels could exacerbate depressive symptoms in AD (Isaacson and Scanziani, 2011).
The role of SCAMP5 in central nervous system diseases
Published in Neurological Research, 2022
Ye Chen, Jiali Fan, Dongqiong Xiao, Xihong Li
Transmembrane cation/H+ exchange activity is mainly attributed to the monovalent Na+(K+)/H+ exchangers (NHEs) in the plasma membrane or intracellular organelles. The human NHE family includes NHE1-NHE5 on the plasma membrane, NHE6-NHE9 on the SVs, and NHE7 and NHE8 on the Golgi apparatus [49]. SCAMP1 and SCAMP2 interact with NHE5 on the cell surface and NHE7 on the Golgi apparatus, respectively. However, SCAMP2 does not interact with NHE6 [20], and SCAMP5 also does not interact with NHE5 [50]. The specificity of this interaction may be due to the difference in the C-terminal domain of the NHE subtypes, which indicates that the C-terminal region of NHEs determines the SCAMP isoforms that interact with them, and SCAMP serves as a selective carrier for NHEs. Previous studies have shown that SVs display NHE activity, which plays an important role in the absorption of glutamate and presynaptic localization [51]. Neurotransmission involves membrane depolarization and the secretion of calcium ion-dependent SVs or LDCVs, with the presynaptic membrane as the target, and subsequent docking and fusion to release neurotransmitters [52].
Datumetine exposure alters hippocampal neurotransmitters system in C57BL/6 mice
Published in Drug and Chemical Toxicology, 2022
Azeez Olakunle Ishola, Aminu Imam, Moyosore Salihu Ajao
Electron microscopy studies on the synapse revealed that datumetine exposed animals showed a reduction in the number of viable synapses with 1.0 mg/kg Datumetine animals showing the greatest reduction compared to controls. It is on record that overactivation of NMDAR leads to synaptic loss (Talantova et al.2013, Zhou et al.2013, Lewerenz and Maher 2015). This observation may be due to the persistent interaction of datumetine with NMDAR (Ishola et al.2020). The postsynaptic density was thicker in datumetine exposed animals with a great reduction in presynaptic vesicles. Chemical neurotransmission is through the release of synaptic vesicles (Trkanjec and Demarin 2001, Ikeda and Bekkers 2009) which are tightly regulated by re-uptake back to the presynaptic neurons (Piedras-Renteria et al.2004, Dickman et al.2012, Davis and Muller 2015). Datumetine greatly reducing the number of synaptic vesicles showed that either reuptake of the vesicles is altered, or rate of production is not balanced with the rate of release (Wang et al.2016, Li and Kavalali 2017). Another possible explanation may be that NMDAR binding with datumetine increases the affinity of presynaptic NMDAR for glutamate thereby increasing the release of neurotransmitters (Reimer et al.1998, Takamori 2016).
Towards a functional connectome in Drosophila
Published in Journal of Neurogenetics, 2020
In all animals, receptors situated at the postsynaptic density are not only modulated by pre-synaptically released neurotransmitters, but also by molecules and peptides released extrasynaptically or from other nearby presynaptic sites (Bentley et al., 2016; De-Miguel & Trueta, 2005; Lendvai & Vizi, 2008). Serotonergic neuromodulation occurs by both synaptic communication as well as volume release (Fuxe & Borroto-Escuela, 2016). In the adult fly, serotonin has been shown to nonsynaptically modulate optic lobe neurons (Gschweng et al., 2019). Serotonergic neurons in vertebrates and invertebrates have widespread impacts across different brain areas and modulate many different cells, sometimes in opposing manners. The mechanisms of volume-released neurotransmission can also involve glial cells that contribute by taking up neurotransmitters (Henn & Hamberger, 1971). Though non-synaptic neuromodulation cannot be predicted by the connectome, it can significantly influence neural processing and therefore the functional circuits that give rise to behavior (Bargmann, 2012; Bargmann & Marder, 2013; Marder, 2012).