Progressive noradrenergic degeneration and motor cortical dysfunction in Parkinson’s disease DOI Creative Commons
Wei Zhou, Hong‐Yuan Chu

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

Abstract The locus coeruleus norepinephrine (LC-NE) system plays an important role in regulating brain function, and its neuronal loss has been well-documented Parkinson’s disease (PD). LC-NE neurodegeneration is believed to underlie various nonmotor symptoms people with PD, including neuropsychiatric deficits, sleep disruptions, cognitive impairments. Of particular interest, neurons send intensive axonal projections the motor regions of cerebral cortex. However, how NE depletion cortex contributes PD pathophysiology remains poorly understood. In addition, recent studies provided increasing mechanistic insights into secondary changes as degenerates, which might involve interaction dopaminergic signaling during chronic course disease. present article, we briefly discuss clinical preclinical that support critical roles cortical dysfunction both deficits Parkinsonian states. We focus our discussion on potential impact function subsequent symptom manifestation. Last, propose future research directions can advance understanding by integrating noradrenergic degeneration.

Language: Английский

Stress and Inflammation Target Dorsolateral Prefrontal Cortex Function: Neural Mechanisms Underlying Weakened Cognitive Control DOI Creative Commons
Mary Kate P. Joyce, Stacy Uchendu,

Amy Arnsten

et al.

Biological Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Language: Английский

Citations

11
Restraint stress effects on glutamate signaling protein levels in the rats’ frontal cortex: Does β1 adrenoceptor activity matter? DOI Creative Commons
Agnieszka Zelek-Molik, A Gàdek-Michalska, Michał Wilczkowski

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 6, 2025

Stress-evoked dysfunctions of the frontal cortex (FC) are correlated with changes in functioning glutamatergic system, and evidence demonstrates that noradrenergic transmission is an important regulator this process. In current study, we adopted a restraint stress (RS) model male Wistar rats to investigate whether blockade β1 adrenergic receptors (β1AR) betaxolol (BET) stressed animals influences body's response expression selected signaling proteins medial prefrontal (mPFC). The study was divided into two parts. first part, were exposed RS for 3, 7, or 14 days, glutamate (p(S845)/t GluA1, p(Y1472)/t GluN2B, VGLUT1, VGLUT2) FC analyzed determine optimal duration studying mechanisms hypofrontality. second BET (5 mg/kg, p. o.) administered during last 8 days immediately after RS. reaction assessed by analyzing body weight blood levels adrenocorticotropic hormone (ACTH) corticosterone (CORT). Behavioral responses evaluated using novel object recognition (NOR) elevated plus maze (EPM) tests. impact on p(Y530)/t Fyn p (S133)/t CREB mPFC measured via Western blotting. part demonstrated decreased level RS, following initial increase observed 7 Results from revealed chronic reduced weight, impaired memory NOR test, augmented ACTH, increased p(Y530) mPFC. However, β1AR did not alter effects gain, cognitive function, Fyn. normalized only concentration ACTH. These results suggest kinase activity, indicated phosphorylation at Y530, underlies stress-evoked downregulation GluN2B manner independent activity.

Language: Английский

Citations

1
The role of Foxo3a in neuron-mediated cognitive impairment DOI Creative Commons
Qinqin Liu, Guihua Wu,

Xiaochun Wang

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: June 19, 2024

Cognitive impairment (COI) is a prevalent complication across spectrum of brain disorders, underpinned by intricate mechanisms yet to be fully elucidated. Neurons, the principal cell population nervous system, orchestrate cognitive processes and govern balance. Extensive inquiry has spotlighted involvement Foxo3a in COI. The regulatory cascade transactivation implicates multiple downstream signaling pathways encompassing mitochondrial function, oxidative stress, autophagy, apoptosis, collectively affecting neuronal activity. Notably, expression activity profile are subject modulation via various modalities, including methylation promoter, phosphorylation acetylation protein. Furthermore, upstream such as PI3K/AKT, SIRT family, diverse micro-RNAs intricately interface with Foxo3a, engendering alterations function. Through several routes, regulates dynamics, thereby modulating onset or amelioration COI Alzheimer’s disease, stroke, ischemic injury, Parkinson’s traumatic injury. potential therapeutic target, clinical drugs small molecules have been preliminarily shown cognitive-enhancing effects that indirectly affect Foxo3a. Particularly noteworthy randomized, controlled, placebo trials illustrating significant enhancement achievable through autophagy modulation. Here, we discussed role neuron-mediated common cognitively impaired diseases.

Language: Английский

Citations

5
The effects of amyloidosis and aging on glutamatergic and GABAergic synapses, and interneurons in the barrel cortex and non-neocortical brain regions DOI Creative Commons

Tao Qu

Frontiers in Neuroanatomy, Journal Year: 2025, Volume and Issue: 19

Published: Feb. 12, 2025

Previous studies on changes in the distribution of GABAergic interneurons and excitation/inhibition (E/I) balance Alzheimer’s disease (AD) aging were mainly conducted neocortex hippocampus. However, limbic system is primary crucial location for AD progression. Therefore, this study, we utilized mouse models to investigate E/I parvalbumin (PV)- somatostatin (SST)-expressing cells S1BF (barrel field somatosensory cortex, barrel cortex), CA1 hippocampal area brain regions beyond hippocampus, including retrosplenial cortex (RSC, which composed RSG RSA), piriform (Pir), amygdala (BMA), hypothalamus (DM). We discovered that amyloidosis may disrupt alignment excitatory pre- postsynaptic quantities. Amyloidosis reduces quantity synapses SST cells, but does not impact counts PV cells. By contrast, linked a decline synapses, I/E ratios, affects BMA, while harm all studied regions, S1BF, RSC, Pir, DM. Aging mostly ratios DM,

Language: Английский

Citations

0
Noradrenergic mechanisms and circuitry of hyperkatifeia in alcohol use disorder DOI Creative Commons
Florence P. Varodayan, Chloe M. Erikson,

Marcis V Scroger

et al.

Biological Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

1
Progressive noradrenergic degeneration and motor cortical dysfunction in Parkinson’s disease DOI Creative Commons
Wei Zhou, Hong‐Yuan Chu

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

Abstract The locus coeruleus norepinephrine (LC-NE) system plays an important role in regulating brain function, and its neuronal loss has been well-documented Parkinson’s disease (PD). LC-NE neurodegeneration is believed to underlie various nonmotor symptoms people with PD, including neuropsychiatric deficits, sleep disruptions, cognitive impairments. Of particular interest, neurons send intensive axonal projections the motor regions of cerebral cortex. However, how NE depletion cortex contributes PD pathophysiology remains poorly understood. In addition, recent studies provided increasing mechanistic insights into secondary changes as degenerates, which might involve interaction dopaminergic signaling during chronic course disease. present article, we briefly discuss clinical preclinical that support critical roles cortical dysfunction both deficits Parkinsonian states. We focus our discussion on potential impact function subsequent symptom manifestation. Last, propose future research directions can advance understanding by integrating noradrenergic degeneration.

Language: Английский

Citations

0