Glutamatergic Transmission in Brain Development and Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Tissues and Organs".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 2797

Special Issue Editors


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Guest Editor
Harrison College of Pharmacy, Auburn University, Auburn, AL, USA
Interests: long-term consequences of prenatal exposure to cannabis; synaptic and network alterations associated with cognitive dysfunction in aging and Alzheimer’s disease; role of hyperexcitability in mediating neurodegeneration; identification of sensitive behavioral tasks for assessment of cognitive impairment; increasing research opportunities for underrepresented minorities

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Guest Editor
School of Pharmaceutical and Health Sciences, Keck Graduate Institute, Claremont Colleges, Claremont, CA 91711, USA
Interests: glutamatergic transmission; AMPA receptor; neuroscience

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Guest Editor
College of Science and Mathematics, Kennesaw State University, Kennesaw, GA, USA
Interests: molecular mechanisms of synaptic deregulation and deficits in learning and memory in conditions (such as aging, diabetes, obesity, Alzheimer’s disease, prenatal alcohol exposure, prenatal nicotine exposure, and prenatal cannabinoid exposure)

Special Issue Information

Dear Colleagues,

Neurodegenerative diseases are becoming more common as advanced medical techniques allow humans to age significantly. Among them are Alzheimer’s disease (AD), Parkinson’s disease (PD) and many more. These diseases affect millions throughout the world. In the US alone, an estimated 6.2 million people might be diagnosed with AD in the coming decade. According to recent studies, around 1 million people are currently living with PD and the number is expected to increase. These diseases generally occur as ageing progresses; however, numerous cases of early onset have also been noted. The pathophysiology of these diseases involves altered macro- and micro-structures of the neural networks in specific brain areas, known and unknown mutations in proteins and receptors leading to their misfolding or malfunction, overall neuronal damage, and loss of plasticity, as well as altered balance in the excitatory and inhibitory neurotransmission systems in the brain mainly controlled by glutamate and gamma-aminobutyric acid receptors. In this Special Issue dedicated to these complex disorders, we invite research articles and reviews from eminent researchers to disseminate their findings through our publication that are focused on novel and cutting-edge findings that investigate and answer questions about these diseases that are clinically and biologically significant.

Dr. Miranda Nicole Reed
Dr. Subhrajit Bhattacharya
Dr. Vishnu Suppiramaniam
Guest Editors

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Published Papers (2 papers)

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Research

16 pages, 856 KiB  
Article
Associations of Plasma Glutamatergic Metabolites with Alpha Desynchronization during Cognitive Interference and Working Memory Tasks in Asymptomatic Alzheimer’s Disease
by Vincent Sonny Leong, Jiaquan Yu, Katherine Castor, Abdulhakim Al-Ezzi, Xianghong Arakaki and Alfred Nji Fonteh
Cells 2024, 13(11), 970; https://doi.org/10.3390/cells13110970 - 4 Jun 2024
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Abstract
Electroencephalogram (EEG) studies have suggested compensatory brain overactivation in cognitively healthy (CH) older adults with pathological beta-amyloid(Aβ42)/tau ratios during working memory and interference processing. However, the association between glutamatergic metabolites and brain activation proxied by EEG signals has not been thoroughly [...] Read more.
Electroencephalogram (EEG) studies have suggested compensatory brain overactivation in cognitively healthy (CH) older adults with pathological beta-amyloid(Aβ42)/tau ratios during working memory and interference processing. However, the association between glutamatergic metabolites and brain activation proxied by EEG signals has not been thoroughly investigated. We aim to determine the involvement of these metabolites in EEG signaling. We focused on CH older adults classified under (1) normal CSF Aβ42/tau ratios (CH-NATs) and (2) pathological Aβ42/tau ratios (CH-PATs). We measured plasma glutamine, glutamate, pyroglutamate, and γ-aminobutyric acid concentrations using tandem mass spectrometry and conducted a correlational analysis with alpha frequency event-related desynchronization (ERD). Under the N-back working memory paradigm, CH-NATs presented negative correlations (r = ~−0.74–−0.96, p = 0.0001–0.0414) between pyroglutamate and alpha ERD but positive correlations (r = ~0.82–0.95, p = 0.0003–0.0119) between glutamine and alpha ERD. Under Stroop interference testing, CH-NATs generated negative correlations between glutamine and left temporal alpha ERD (r = −0.96, p = 0.037 and r = −0.97, p = 0.027). Our study demonstrated that glutamine and pyroglutamate levels were associated with EEG activity only in CH-NATs. These results suggest cognitively healthy adults with amyloid/tau pathology experience subtle metabolic dysfunction that may influence EEG signaling during cognitive challenge. A longitudinal follow-up study with a larger sample size is needed to validate these pilot studies. Full article
(This article belongs to the Special Issue Glutamatergic Transmission in Brain Development and Disease)
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21 pages, 3773 KiB  
Article
Prenatal Cannabinoid Exposure Elicits Memory Deficits Associated with Reduced PSA-NCAM Expression, Altered Glutamatergic Signaling, and Adaptations in Hippocampal Synaptic Plasticity
by Priyanka D. Pinky, Jenna Bloemer, Warren D. Smith, Yifeng Du, Ryan T. Heslin, Sharay E. Setti, Jeremiah C. Pfitzer, Kawsar Chowdhury, Hao Hong, Subhrajit Bhattacharya, Muralikrishnan Dhanasekaran, Alexander Dityatev, Miranda N. Reed and Vishnu Suppiramaniam
Cells 2023, 12(21), 2525; https://doi.org/10.3390/cells12212525 - 26 Oct 2023
Cited by 1 | Viewed by 1728
Abstract
Cannabis is now one of the most commonly used illicit substances among pregnant women. This is particularly concerning since developmental exposure to cannabinoids can elicit enduring neurofunctional and cognitive alterations. This study investigates the mechanisms of learning and memory deficits resulting from prenatal [...] Read more.
Cannabis is now one of the most commonly used illicit substances among pregnant women. This is particularly concerning since developmental exposure to cannabinoids can elicit enduring neurofunctional and cognitive alterations. This study investigates the mechanisms of learning and memory deficits resulting from prenatal cannabinoid exposure (PCE) in adolescent offspring. The synthetic cannabinoid agonist WIN55,212-2 was administered to pregnant rats, and a series of behavioral, electrophysiological, and immunochemical studies were performed to identify potential mechanisms of memory deficits in the adolescent offspring. Hippocampal-dependent memory deficits in adolescent PCE animals were associated with decreased long-term potentiation (LTP) and enhanced long-term depression (LTD) at hippocampal Schaffer collateral-CA1 synapses, as well as an imbalance between GluN2A- and GluN2B-mediated signaling. Moreover, PCE reduced gene and protein expression of neural cell adhesion molecule (NCAM) and polysialylated-NCAM (PSA-NCAM), which are critical for GluN2A and GluN2B signaling balance. Administration of exogenous PSA abrogated the LTP deficits observed in PCE animals, suggesting PSA mediated alterations in GluN2A- and GluN2B- signaling pathways may be responsible for the impaired hippocampal synaptic plasticity resulting from PCE. These findings enhance our current understanding of how PCE affects memory and how this process can be manipulated for future therapeutic purposes. Full article
(This article belongs to the Special Issue Glutamatergic Transmission in Brain Development and Disease)
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