Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102468 - 102468
Published: Aug. 31, 2024
Language: Английский
Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(8), P. 3182 - 3191
Published: April 28, 2022
Language: Английский
Citations
33
Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(10), P. 8123 - 8143
Published: March 12, 2024
Language: Английский
Citations
8
International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(11), P. 6143 - 6143
Published: May 30, 2022
A growing body of evidence demonstrates the important role noradrenergic system in pathogenesis many neurodegenerative processes, especially Alzheimer’s disease, due to its ability control glial activation and chemokine production resulting anti-inflammatory neuroprotective effects. Noradrenaline involvement this disease was first proposed after finding deficits neurons locus coeruleus from patients. Based on this, it has been hypothesized that early loss projections subsequent reduction noradrenaline brain levels contribute cognitive dysfunctions progression neurodegeneration. Several studies have focused analyzing development disease. In review we summarize some most relevant data describing alterations normally occurring as well experimental which concentration modified order further analyze how these affect behavior viability different nervous cells. The combination here presented suggests maintenance adequate central constitutes a key factor endogenous defense systems help prevent or delay For reason, use modulating drugs is an interesting alternative therapeutic option for
Language: Английский
Citations
27
Clinical Interventions in Aging, Journal Year: 2023, Volume and Issue: Volume 18, P. 713 - 728
Published: May 1, 2023
Abstract: Alzheimer’s disease (AD), the most common cause of dementia and fifth leading death in adult population has a complex pathophysiological link with hypertension (HTN). A growing volume published literature on parallel elevation blood pressure (BP), amyloid plaques, neurofibrillary tangles formation post-middle human brain cells developed new, widely accepting foundations this association. In particular, HTN elderly life mediates cerebral flow dysfunction, neuronal significant decline cognitive impairment, primarily late-life populace, governing onset AD. Thus, is an established risk factor for Considering impact AD, 1.89 million deaths annually, failure palliative therapies to cure scientific research community looking adopt integrated approaches target early modified factors like reduce AD burden. The current review highlights significance HTN-based prevention lowering burden by providing comprehensive overview physiological relationship between in-detail explanation role applications pathological biomarkers clinical will gain worth presenting new insights inclusive discussion correlation impairment. It increase across wider audience expand understanding Keywords: disease, hypertension, population,
Language: Английский
Citations
16
Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown
Published: July 16, 2024
Alzheimer's disease (AD) is a progressive neurodegenerative disease. The accumulation of amyloid-β (Aβ) plaques and tau neurofibrillary tangles are the key players responsible for pathogenesis Aβ affect balance in chemical neurotransmitters brain. Thus, current review examined role discusses alterations neurochemical activity cross talk with their receptors transporters. In presence tangles, changes may occur expression neuronal which turn triggers excessive release glutamate into synaptic cleft contributing to cell death damage. GABAergic system also be affected by AD pathology similar way. addition, decreased cholinergic dysfunction dopamine neurotransmission contribute damage cognitive function. Moreover, deficiencies noradrenergic neurons within locus coeruleus suggests that stimulation could useful addressing its pathophysiology. regulation melatonin, known effectiveness enhancing function preventing accumulation, along involvement serotonergic histaminergic cognition memory, becomes remarkable promoting AD. Additionally, nitric oxide adenosine-based therapeutic approaches play protective neuroinflammation. Overall, neurotransmitter-based strategies emerge as pivotal neurotransmitter homeostasis context This discussed potential drugs effective slowing correcting processes targeting imbalance Therefore, serve future strategy tackle
Language: Английский
Citations
5
Cells, Journal Year: 2023, Volume and Issue: 12(2), P. 284 - 284
Published: Jan. 11, 2023
Drugs enhancing the availability of noradrenaline are gaining prominence in therapy chronic neuropathic pain. However, underlying mechanisms not well understood, and research has thus far focused on α2-adrenergic receptors neuronal excitability. Adrenergic also expressed glial cells, but their roles toward antinociception deciphered. This study addresses contribution β2-adrenergic (β2-ARs) to therapeutic modulation pain mice. We report that selective activation β2-ARs with Formoterol inhibits pro-inflammatory signaling microglia ex vivo nerve injury-induced structural remodeling functional vivo. Systemic delivery behaviors related pain, such as mechanical hypersensitivity, cold allodynia aversive component reverses chronically established Using conditional gene targeting for microglia-specific deletion β2-ARs, we demonstrate anti-allodynic effects primarily mediated by microglia. Although reduces astrogliosis at late stages these functions unrelated β2-AR Our results underline value developing microglial agonists relief from clarify mechanistic underpinnings.
Language: Английский
Citations
12
Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 152, P. 105311 - 105311
Published: July 10, 2023
The locus coeruleus (LC) is a small brainstem structure located in the lower pons and main source of noradrenaline (NA) brain. Via its phasic tonic firing, it modulates cognition autonomic functions involved brain's immune response. extent degeneration to LC healthy ageing remains unclear, however, noradrenergic dysfunction may contribute pathogenesis Alzheimer's (AD) Parkinson's disease (PD). Despite their differences progression at later stages, early involvement lead comparable behavioural symptoms such as preclinical sleep problems neuropsychiatric result AD PD pathology. In this review, we draw attention mechanisms that underlie ageing, PD. We aim motivate future research investigate how system play pivotal role which also be relevant other neurodegenerative diseases.
Language: Английский
Citations
12
Biology, Journal Year: 2023, Volume and Issue: 12(8), P. 1154 - 1154
Published: Aug. 21, 2023
Cognitive impairment (CI) shares common cardiovascular risk factors with acute myocardial infarction (AMI), and is increasingly prevalent in our ageing population. Whilst AMI associated increased rates of CI, CI remains underreported infrequently identified patients AMI. In this review, we discuss the evidence surrounding its links to dementia including pathophysiology, factors, management interventions. Vascular dysregulation plays a major role atherosclerosis, platelet activation, microinfarcts perivascular inflammation resulting neurovascular unit dysfunction, disordered homeostasis dysfunctional neurohormonal response. This subsequently affects perfusion pressure, enlarged periventricular spaces hippocampal sclerosis. The activation seen coronary artery disease (CAD) can also result amyloid-β protein deposition which Alzheimer’s Dementia. Post-AMI, reduced blood pressure left ventricular ejection fraction cause chronic cerebral hypoperfusion, failure normal circulatory autoregulatory mechanisms. Patients who undergo revascularization (percutaneous intervention or bypass surgery) are at for post-procedure cognitive impairment, though whether related itself underlying debated. Mortality higher AMI, post-AMI more elderly heart failure. Medical (antiplatelet, statin, renin-angiotensin system inhibitors, cardiac rehabilitation) reduce CI; however, beta-blockers may be functional decline existing CI. early identification those present important, as subsequent tailoring strategies potentially improve outcomes well guide prognosis.
Language: Английский
Citations
11
Aging Cell, Journal Year: 2024, Volume and Issue: 24(1)
Published: Sept. 23, 2024
The locus coeruleus (LC)-prefrontal cortex (PFC) circuitry is crucial for cognition, planning, posture and mobility. This study examines the role of norepinephrine (NE) in elucidating neurobiological basis age-related cognitive motor declines. Aged mice exhibited reduced spatial learning, impaired memory, decreased physical endurance, notable changes locomotor behavior. neurochemical foundations these deficits were investigated through fast-scan cyclic voltammetry to measure NE release PFC LC, both vivo brain slices. Additionally, oxygen levels monitored as a proxy neuronal function, analyzed extracellular space via microdialysis total content PFC. frequency-dependent increase upon LC stimulation, suggesting alterations neural responsiveness due aging. We also recorded slower reuptake rates increased activity, indicated by higher facilitated neuron activation membrane depolarization whole-cell patch-clamp. To understand LC-driven surges with aging, we examined expression two proteins critical presynaptic reuptake: α2a-adrenergic receptor transporter. Both showed significant decrease These findings support concept that aging significantly alters structural functional dynamics within LC-PFC circuit, impacting modulation which may underlie observed declines functions populations.
Language: Английский
Citations
4
Physiological Reports, Journal Year: 2025, Volume and Issue: 13(1)
Published: Jan. 1, 2025
Abstract Inflammation and a metabolic shift from oxidative metabolism to glycolysis are common in the ischemic heart, latter partly controlled by pyruvate kinase (muscle, PKM). We previously identified alternative splicing promoting PKM2 isoform after myocardial infarction (MI). examined role of physiological upregulation MI, modeled ligation left anterior descending coronary artery, using global knockout (PKM2 −/− ) mice. Echocardiography showed similar cardiac function between control mice MI. However, infarcted hearts had increased abundances transcripts associated with stress immune responses. Immunohistochemistry revealed greater abundance macrophages prior small increase CD86 + hearts. Elevated baseline plasma IL‐6, IL‐1β, C‐reactive protein, 3 days post‐MI, were observed Oxidative lipid products also elevated hearts, while antioxidant glutathione peroxidase 4 was reduced. Greater fibrosis seen 28 These findings suggest Pkm2 ablation primes heart for stress, inflammation, post‐MI. The natural may mitigate reducing highlighting its protective heart.
Language: Английский
Citations
0