ORCID Profile
0000-0003-4021-3636
Current Organisations
La Trobe University
,
Stanford University
,
Epigenes Australia Pty Ltd
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Publisher: MDPI AG
Date: 04-11-2022
DOI: 10.3390/NU14214670
Abstract: Further examination of the molecular regulators of long-term calorie restriction (CR), reported to have an anxiolytic effect, may highlight novel therapeutic targets for anxiety disorders. Here, adult male Hooded Wistar rats were exposed to a 25% CR whilst anxiety-like behaviour was assessed at 6-, 12-, and 18-months of age via the elevated plus maze, open field, and acoustic startle tests. Next-generation sequencing was then used to measure transcriptome-wide gene expression in the hypothalamus, amygdala, pituitary, and adrenal glands. Results showed an anxiolytic behavioural profile across early, middle, and late adulthood by CR, with the strongest effects noted at 6-months. Transcriptomic analysis by seven attribute weighting algorithms, including Info Gain Ratio, Rule, Chi Squared, Gini Index, Uncertainty, Relief, and Info Gain, led to the development of a signature of long-term CR, independent of region. Complement C1q A chain (C1qa), an extracellular protein, expression was significantly decreased by CR in most regions examined. Furthermore, text mining highlighted the positive involvement of C1qa in anxiety, depression, neurodegeneration, stress, and ageing, collectively identifying a suitable biomarker candidate for CR. Overall, the current study identified anxiety-related phenotypic changes and a novel transcriptome signature of long-term CR, indicating potential therapeutic targets for anxiety, depression, and neurodegeneration.
Publisher: Springer Science and Business Media LLC
Date: 14-08-2018
Publisher: Cold Spring Harbor Laboratory
Date: 19-03-2013
Abstract: We used Pavlovian counterconditioning in rats to identify the neural mechanisms for appetitive–aversive motivational interactions. In Stage I, rats were trained on conditioned stimulus (CS)–food (unconditioned stimulus [US]) pairings. In Stage II, this appetitive CS was transformed into a fear CS via pairings with footshock. The development of fear responses was retarded in rats that had received Stage I appetitive training. This counterconditioning was associated with increased levels of phosphorylated mitogen activated protein kinase immunoreactivity (pMAPK-IR) in several brain regions, including midline thalamus, rostral agranular insular cortex (RAIC), lateral amygdala, and nucleus accumbens core and shell, but decreased expression in the ventrolateral quadrant of the midbrain periaqueductal gray. These brain regions showing differential pMAPK-IR have previously been identified as part of the fear prediction error circuit. We then examined the causal role of RAIC MAPK in fear learning and showed that Stage II fear learning was prevented by RAIC infusions of the MEK inhibitor PD098059 (0.5 µg/hemisphere). Taken together, these results show that there are opponent interactions between the appetitive and aversive motivational systems during fear learning and that the transformation of a reward CS into a fear CS is linked to heightened activity in the fear prediction error circuit.
Publisher: Elsevier BV
Date: 10-2020
Publisher: American Psychological Association (APA)
Date: 04-2017
DOI: 10.1037/BNE0000185
Publisher: Elsevier BV
Date: 05-2015
Publisher: American Psychological Association (APA)
Date: 2012
DOI: 10.1037/A0028341
Abstract: The existence of value coding and salience coding neurons in the mammalian brain, including in habenula and ventral tegmental area, has sparked considerable interest in the interactions that occur between Pavlovian appetitive and aversive conditioning. Here we studied these appetitive-aversive interactions at the behavioral level by assessing the learning that occurs when a Pavlovian appetitive conditioned stimulus (conditional stimulus, CS) serves as a CS for shock in Pavlovian fear conditioning. A Pavlovian appetitive CS was retarded in the rate at which it could be transformed into a fear CS (counterconditioning), but the presence of the appetitive CS augmented fear learning to a concurrently presented neutral CS (superconditioning). Retardation of fear learning was not alleviated by manipulations designed to restore the associability of the appetitive CS before fear conditioning but was alleviated by manipulations designed to increase the aversive quality of the shock unconditioned stimulus (US). These findings are consistent with opponent interactions between the appetitive and aversive motivational systems and provide a behavioral approach for assessing the neural correlates of these appetitive-aversive interactions.
Publisher: Frontiers Media SA
Date: 03-11-2015
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.EXPNEUROL.2019.113013
Abstract: The piriform cortex is a distinct brain region that plays a key role in the sense of smell. The piriform cortex is the major part of primary olfactory cortex and has broad connections that extend beyond the olfactory regions into limbic and fronto-temporal cortical networks. Numerous studies have described these anatomical connections via microscopic imaging and tracer studies. More recently, macroscopic anatomical imaging studies have demonstrated changes in the piriform cortex in humans with focal epilepsy as well as in animal models, suggesting this brain region can play a critical role in epileptogenesis. This review examines the imaging methods and techniques that have been most informative, leading to our current understanding of the anatomy and sub sions of the piriform cortex as well as its connections to other brain structures, and the abnormalities that can be detected in the setting of epilepsy.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 07-2020
DOI: 10.1126/SCITRANSLMED.ABA6676
Abstract: Monomeric insulin stabilized with polymeric excipient exhibits increased stability and faster pharmacokinetics than current rapid-acting insulins.
Publisher: American Chemical Society (ACS)
Date: 08-09-2017
DOI: 10.1021/JACS.7B04821
Abstract: Kinetics and thermodynamics in supramolecular systems are intimately linked, yet both are independently important for application in sensing assays and stimuli-responsive switching/self-healing of materials. Host-guest interactions are of particular interest in many water-based materials, sensing, and drug delivery applications. Herein we investigate the binding dynamics of a variety of electron-rich aromatic moieties forming hetero-ternary complexes with the macrocycle cucurbit[8]uril (CB[8]) and an auxiliary guest, dimethyl viologen, with high selectivity and equilibrium binding constants (K
Publisher: Frontiers Media SA
Date: 22-02-2017
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.YEBEH.2019.05.032
Abstract: The objective of the study were to investigate patterns of multiunit cluster firing in the piriform cortex (PC) and mediodorsal thalamus (MDT) in a rat model of genetic generalized epilepsy (GGE) with absence seizures and to assess whether these regions contribute to the initiation or spread of generalized epileptiform discharges. Multiunit clusters and their corresponding local field potentials (LFPs) were recorded from microelectrode arrays implanted in the PC and MDT in urethane anesthetized Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and nonepileptic control (NEC) rats. Peristimulus time histograms (PSTHs) and cross-correlograms were used to observe transient changes in both the rate of firing and synchrony over time. The phase locking of multiunit clusters to LFP signals (spike-LFP phase locking) was calculated for frequency bands associated with olfactory communication between the two brain regions. There were significant increases in both rate of firing and synchronous activity at the onset of generalized epileptiform discharges in both PC and MDT. Prior to and following these increases in synchronous activity, there were periods of suppression. Significant increases in spike-LFP phase locking were observed within the PC prior to the onset of epileptiform discharges across all spectral bands. There were also significant increases in spike-LFP phase locking within the theta band of the MDT prior to onset. Between the two brain regions, there was a significant decrease in spike-LFP phase locking -0.5 s prior to onset in the theta band which coincided with a significant elevation in spike-LFP phase locking in the gamma band. Both the PC and MDT are engaged in the absence epilepsy network. Early spike-LFP phase locking between these two brain regions suggests potential involvement in the initiation of seizure activity.
Publisher: Elsevier BV
Date: 2018
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
Location: Australia
No related grants have been discovered for Helen Nasser.