Localization of endogenous amyloid-β to the coeruleo-cortical pathway: consequences of noradrenergic depletion

Ross, Jennifer A.; Reyes, Beverly A.S.; Thomas, Steven; Bockstaele, Elisabeth J. Van

doi:10.1007/s00429-017-1489-9

Cited by 11 publications

(9 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Western blot analysis was conducted in parallel with ELISA studies to determine protein expression levels of the NE synthesizing enzyme, DβH, in these animals. These results were recently reported, and indicate that DβH protein expression in DSP-4-treated animals was significantly reduced compared to saline and naïve rats (Ross et al, 2017). It is possible that the effects of NE depletion on the eCB system in the PFC are indirect.…”

Section: Discussionsupporting

confidence: 83%

Noradrenergic depletion causes sex specific alterations in the endocannabinoid system in the Murine prefrontal cortex

Urquhart

Ross

Reyes

et al. 2019

Neurobiology of Stress

View full text Add to dashboard Cite

Brain endocannabinoids (eCB), acting primarily via the cannabinoid type 1 receptor (CB1r), are involved in the regulation of many physiological processes, including behavioral responses to stress. A significant neural target of eCB action is the stress-responsive norepinephrine (NE) system, whose dysregulation is implicated in myriad psychiatric and neurodegenerative disorders. Using Western blot analysis, the protein expression levels of a key enzyme in the biosynthesis of the eCB 2-arachidonoylglycerol (2-AG), diacylglycerol lipase-α (DGL-α), and two eCB degrading enzymes monoacylglycerol lipase (MGL) and fatty acid amide hydrolase (FAAH) were examined in a mouse model that lacks the NE-synthesizing enzyme, dopamine β-hydroxylase (DβH-knockout, KO) and in rats treated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4). In the prefrontal cortex (PFC), DGL-α protein expression was significantly increased in male and female DβH-KO mice (P < 0.05) compared to wild-type (WT) mice. DβH-KO male mice showed significant decreases in FAAH protein expression compared to WT male mice. Consistent with the DβH-KO results, DGL-α protein expression was significantly increased in male DSP-4-treated rats (P < 0.05) when compared to saline-treated controls. MGL and FAAH protein expression levels were significantly increased in male DSP-4 treated rats compared to male saline controls. Finally, we investigated the anatomical distribution of MGL and FAAH in the NE containing axon terminals of the PFC using immunoelectron microscopy. MGL was predominantly within presynaptic terminals while FAAH was localized to postsynaptic sites. These results suggest that the eCB system may be more responsive in males than females under conditions of NE perturbation, thus having potential implications for sex-specific treatment strategies of stress-related psychiatric disorders.

show abstract

Section: Discussionsupporting

confidence: 83%

Noradrenergic depletion causes sex specific alterations in the endocannabinoid system in the Murine prefrontal cortex

Urquhart

Ross

Reyes

et al. 2019

Neurobiology of Stress

View full text Add to dashboard Cite

show abstract

“…Our laboratory is the first to have localized endogenous Aβ 42 peptides to LC neurons of the naïve rat in vivo using fluorescence microscopy and immunoelectron microscopy ( 248 ). Using highly sensitive ELISA for Aβ 42 , we demonstrated that NE and Aβ 42 levels positively correlate in the naïve rat.…”

Section: Modern Integrated Perspectives Of Arousal and The Lc-ne Systmentioning

confidence: 99%

The Locus Coeruleus- Norepinephrine System in Stress and Arousal: Unraveling Historical, Current, and Future Perspectives

2021

Self Cite

View full text Add to dashboard Cite

Arousal may be understood on a spectrum, with excessive sleepiness, cognitive dysfunction, and inattention on one side, a wakeful state in the middle, and hypervigilance, panic, and psychosis on the other side. However, historically, the concepts of arousal and stress have been challenging to define as measurable experimental variables. Divergent efforts to study these subjects have given rise to several disciplines, including neurobiology, neuroendocrinology, and cognitive neuroscience. We discuss technological advancements that chronologically led to our current understanding of the arousal system, focusing on the multifaceted nucleus locus coeruleus. We share our contemporary perspective and the hypotheses of others in the context of our current technological capabilities and future developments that will be required to move forward in this area of research.

show abstract

“…As alluded to earlier, altered protein and activity have been reported in both PD and AD. This can occur in several ways such as degeneration of LC noradrenergic neurons, neuroinflammation, and dysregulation of copper levels that are all associated with both neurological diseases (McMillan et al ; Trillo et al ; He et al ; Tang et al ; Peterson and Li ; Ross et al ).…”

Section: Dβh In Neurodegenerative Diseasementioning

confidence: 99%

Dopamine beta‐hydroxylase and its genetic variants in human health and disease

Gonzalez-Lopez

Vrana

2019

Journal of Neurochemistry

View full text Add to dashboard Cite

Dopamine beta-hydroxylase (DbH) is an essential neurotransmitter-synthesizing enzyme that catalyzes the formation of norepinephrine (NE) from dopamine and has been extensively studied since its discovery in the 1950s. NE serves as a neurotransmitter in both the central and peripheral nervous systems and is the precursor to epinephrine synthesis in the brain and adrenal medulla. Alterations in noradrenergic signaling have been linked to both central nervous system and peripheral pathologies. DbH protein, which is found in circulation, can, therefore, be evaluated as a marker of norepinephrine function in a plethora of different disorders and diseases. In many of these diseases, DbH protein availability and activity are believed to contribute to disease presentation or select symptomology and are believed to be under strong genetic control. Alteration in the DbH protein by genetic polymorphisms may result in DbH becoming ratelimiting and directly contributing to lower NE and epinephrine levels and disease. With the completion of the human genome project and the advent of next-generation sequencing, new insights have been gained into the existence of naturally occurring DbH sequencing variants (genetic polymorphisms) in disease. Also, biophysical tools coupled with genetic sequences are illuminating structure-function relationships within the enzyme. In this review, we discuss the role of genetic variants in DbH and its role in health and disease.

show abstract

Localization of endogenous amyloid-β to the coeruleo-cortical pathway: consequences of noradrenergic depletion

Cited by 11 publications

References 77 publications

Noradrenergic depletion causes sex specific alterations in the endocannabinoid system in the Murine prefrontal cortex

Noradrenergic depletion causes sex specific alterations in the endocannabinoid system in the Murine prefrontal cortex

The Locus Coeruleus- Norepinephrine System in Stress and Arousal: Unraveling Historical, Current, and Future Perspectives

Dopamine beta‐hydroxylase and its genetic variants in human health and disease

Contact Info

Product

Resources

About