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The Pharmacology of Neurotransmission: Focus on Synaptic Alterations during Neurodegeneration and Treatments

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (10 October 2020) | Viewed by 30217

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Special Issue Editor

Dr. Jonathan Mapelli

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Guest Editor

Dept Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
Interests: synaptic plasticity; cerebellum; computational neuroscience; neural circuits; synaptic transmission; neuronal excitability; imaging; non-linear microscopy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Brain functionality is inherently bound to the information transmitted among neural circuits, which, in turn, depends on a wide series of factors residing in synaptic connections. It is therefore evident that changes in synaptic functions are critically involved in the emergence of brain functionality as well as neural diseases and pharmacological treatments. In particular, despite their reduced dimensions, synaptic complexes display a huge number of molecular pathways both on the pre- and post-synaptic side, which can be potentially targeted by exogenous molecules, and although several drugs and molecules have been described to interfering with synaptic activity, we are very far from a definitive description.

This Special Issue will accept articles covering different aspects of the pharmacology of neurotransmission, paying particular attention to the effects on synaptic targets in terms of functionality. Manuscripts regarding new synaptic molecular targets, new drugs, treatments of neural disorders or neurodegenerative diseases, and computational effects of drug application will be more than welcome.

This Special Issue aims to focus on both basic science and translational research as well as clinical evidence to have a larger and more inclusive understanding of neurotransmission, allowing to shed light into this complicated and puzzling scenario.

Dr. Jonathan Mapelli
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

synapses
ion channels
neuromodulation
neurons
information transmission
neurotransmitter
synaptic plasticity
mutual information
neurogenerative diseases
neural disorders
neural circuits
synaptic complex
GABA
glutamate
glycine
peptides
synaptic proteins
synaptic vesicles
vesicle release

Published Papers (6 papers)

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Research

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13 pages, 2907 KiB

Open AccessArticle

Age-Dependent Decline in Synaptic Mitochondrial Function Is Exacerbated in Vulnerable Brain Regions of Female 3xTg-AD Mice

by César Espino de la Fuente-Muñoz, Mónica Rosas-Lemus, Perla Moreno-Castilla, Federico Bermúdez-Rattoni, Salvador Uribe-Carvajal and Clorinda Arias

Int. J. Mol. Sci. 2020, 21(22), 8727; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228727 - 19 Nov 2020

Cited by 20 | Viewed by 3426

Abstract

Synaptic aging has been associated with neuronal circuit dysfunction and cognitive decline. Reduced mitochondrial function may be an early event that compromises synaptic integrity and neurotransmission in vulnerable brain regions during physiological and pathological aging. Thus, we aimed to measure mitochondrial function in synapses from three brain regions at two different ages in the 3xTg-AD mouse model and in wild mice. We found that aging is the main factor associated with the decline in synaptic mitochondrial function, particularly in synapses isolated from the cerebellum. Accumulation of toxic compounds, such as tau and Aβ, that occurred in the 3xTg-AD mouse model seemed to participate in the worsening of this decline in the hippocampus. The changes in synaptic bioenergetics were also associated with increased activation of the mitochondrial fission protein Drp1. These results suggest the presence of altered mechanisms of synaptic mitochondrial dynamics and their quality control during aging and in the 3xTg-AD mouse model; they also point to bioenergetic restoration as a useful therapeutic strategy to preserve synaptic function during aging and at the early stages of Alzheimer’s disease (AD). Full article

(This article belongs to the Special Issue The Pharmacology of Neurotransmission: Focus on Synaptic Alterations during Neurodegeneration and Treatments)

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18 pages, 2280 KiB

Open AccessArticle

Tetrapeptide Ac-HAEE-NH₂ Protects α4β2 nAChR from Inhibition by Aβ

by Evgeny P. Barykin, Aleksandra I. Garifulina, Anna P. Tolstova, Anastasia A. Anashkina, Alexei A. Adzhubei, Yuri V. Mezentsev, Irina V. Shelukhina, Sergey A. Kozin, Victor I. Tsetlin and Alexander A. Makarov

Int. J. Mol. Sci. 2020, 21(17), 6272; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21176272 - 29 Aug 2020

Cited by 9 | Viewed by 3340

Abstract

The cholinergic deficit in Alzheimer’s disease (AD) may arise from selective loss of cholinergic neurons caused by the binding of Aβ peptide to nicotinic acetylcholine receptors (nAChRs). Thus, compounds preventing such an interaction are needed to address the cholinergic dysfunction. Recent findings suggest that the ¹¹EVHH¹⁴ site in Aβ peptide mediates its interaction with α4β2 nAChR. This site contains several charged amino acid residues, hence we hypothesized that the formation of Aβ-α4β2 nAChR complex is based on the interaction of ¹¹EVHH¹⁴ with its charge-complementary counterpart in α4β2 nAChR. Indeed, we discovered a ³⁵HAEE³⁸ site in α4β2 nAChR, which is charge-complementary to ¹¹EVHH¹⁴, and molecular modeling showed that a stable Aβ₄₂-α4β2 nAChR complex could be formed via the ¹¹EVHH¹⁴:³⁵HAEE³⁸ interface. Using surface plasmon resonance and bioinformatics approaches, we further showed that a corresponding tetrapeptide Ac-HAEE-NH₂ can bind to Aβ via ¹¹EVHH¹⁴ site. Finally, using two-electrode voltage clamp in Xenopus laevis oocytes, we showed that Ac-HAEE-NH₂ tetrapeptide completely abolishes the Aβ₄₂-induced inhibition of α4β2 nAChR. Thus, we suggest that ³⁵HAEE³⁸ is a potential binding site for Aβ on α4β2 nAChR and Ac-HAEE-NH₂ tetrapeptide corresponding to this site is a potential therapeutic for the treatment of α4β2 nAChR-dependent cholinergic dysfunction in AD. Full article

(This article belongs to the Special Issue The Pharmacology of Neurotransmission: Focus on Synaptic Alterations during Neurodegeneration and Treatments)

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Review

Jump to: Research

21 pages, 1637 KiB

Open AccessReview

Modeling Neurotransmission: Computational Tools to Investigate Neurological Disorders

by Daniela Gandolfi, Giulia Maria Boiani, Albertino Bigiani and Jonathan Mapelli

Int. J. Mol. Sci. 2021, 22(9), 4565; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094565 - 27 Apr 2021

Cited by 7 | Viewed by 3686

Abstract

The investigation of synaptic functions remains one of the most fascinating challenges in the field of neuroscience and a large number of experimental methods have been tuned to dissect the mechanisms taking part in the neurotransmission process. Furthermore, the understanding of the insights of neurological disorders originating from alterations in neurotransmission often requires the development of (i) animal models of pathologies, (ii) invasive tools and (iii) targeted pharmacological approaches. In the last decades, additional tools to explore neurological diseases have been provided to the scientific community. A wide range of computational models in fact have been developed to explore the alterations of the mechanisms involved in neurotransmission following the emergence of neurological pathologies. Here, we review some of the advancements in the development of computational methods employed to investigate neuronal circuits with a particular focus on the application to the most diffuse neurological disorders. Full article

(This article belongs to the Special Issue The Pharmacology of Neurotransmission: Focus on Synaptic Alterations during Neurodegeneration and Treatments)

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28 pages, 942 KiB

Open AccessReview

Synaptic Reshaping and Neuronal Outcomes in the Temporal Lobe Epilepsy

by Elisa Ren and Giulia Curia

Int. J. Mol. Sci. 2021, 22(8), 3860; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22083860 - 08 Apr 2021

Cited by 21 | Viewed by 4065

Abstract

Temporal lobe epilepsy (TLE) is one of the most common types of focal epilepsy, characterized by recurrent spontaneous seizures originating in the temporal lobe(s), with mesial TLE (mTLE) as the worst form of TLE, often associated with hippocampal sclerosis. Abnormal epileptiform discharges are the result, among others, of altered cell-to-cell communication in both chemical and electrical transmissions. Current knowledge about the neurobiology of TLE in human patients emerges from pathological studies of biopsy specimens isolated from the epileptogenic zone or, in a few more recent investigations, from living subjects using positron emission tomography (PET). To overcome limitations related to the use of human tissue, animal models are of great help as they allow the selection of homogeneous samples still presenting a more various scenario of the epileptic syndrome, the presence of a comparable control group, and the availability of a greater amount of tissue for in vitro/ex vivo investigations. This review provides an overview of the structural and functional alterations of synaptic connections in the brain of TLE/mTLE patients and animal models. Full article

(This article belongs to the Special Issue The Pharmacology of Neurotransmission: Focus on Synaptic Alterations during Neurodegeneration and Treatments)

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23 pages, 992 KiB

Open AccessReview

Understanding the Effects of Anesthesia on Cortical Electrophysiological Recordings: A Scoping Review

by Vincenzo Sorrenti, Claudia Cecchetto, Marta Maschietto, Stefano Fortinguerra, Alessandro Buriani and Stefano Vassanelli

Int. J. Mol. Sci. 2021, 22(3), 1286; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031286 - 28 Jan 2021

Cited by 22 | Viewed by 5762

Abstract

General anesthesia in animal experiments is an ethical must and is required for all the procedures that are likely to cause more than slight or momentary pain. As anesthetics are known to deeply affect experimental findings, including electrophysiological recordings of brain activity, understanding their mechanism of action is of paramount importance. It is widely recognized that the depth and type of anesthesia introduce significant bias in electrophysiological measurements by affecting the shape of both spontaneous and evoked signals, e.g., modifying their latency and relative amplitude. Therefore, for a given experimental protocol, it is relevant to identify the appropriate anesthetic, to minimize the impact on neuronal circuits and related signals under investigation. This review focuses on the effect of different anesthetics on cortical electrical recordings, examining their molecular mechanisms of action, their influence on neuronal microcircuits and, consequently, their impact on cortical measurements. Full article

(This article belongs to the Special Issue The Pharmacology of Neurotransmission: Focus on Synaptic Alterations during Neurodegeneration and Treatments)

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13 pages, 1000 KiB

Open AccessReview

Presynaptic Inhibition of Pain and Touch in the Spinal Cord: From Receptors to Circuits

by Antonella Comitato and Rita Bardoni

Int. J. Mol. Sci. 2021, 22(1), 414; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010414 - 02 Jan 2021

Cited by 24 | Viewed by 9192

Abstract

Sensory primary afferent fibers, conveying touch, pain, itch, and proprioception, synapse onto spinal cord dorsal horn neurons. Primary afferent central terminals express a wide variety of receptors that modulate glutamate and peptide release. Regulation of the amount and timing of neurotransmitter release critically affects the integration of postsynaptic responses and the coding of sensory information. The role of GABA (γ-aminobutyric acid) receptors expressed on afferent central terminals is particularly important in sensory processing, both in physiological conditions and in sensitized states induced by chronic pain. During the last decade, techniques of opto- and chemogenetic stimulation and neuronal selective labeling have provided interesting insights on this topic. This review focused on the recent advances about the modulatory effects of presynaptic GABAergic receptors in spinal cord dorsal horn and the neural circuits involved in these mechanisms. Full article

(This article belongs to the Special Issue The Pharmacology of Neurotransmission: Focus on Synaptic Alterations during Neurodegeneration and Treatments)

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