Acetylcholine In Cerebrospinal Fluid Research Articles

Clinical features and neurobiochemical mechanisms of olfactory dysfunction in patients with Parkinson disease.

This study aimed to investigate clinical features, influencing factors and neurobiochemical mechanisms of olfactory dysfunction (OD) in Parkinson disease (PD). Total 39 patients were divided into thePD with OD (PD-OD) and PD with no OD (PD-nOD) groups according to overall olfactory function, including threshold, discrimination and identification, assessed by Sniffin' Sticks test. Motor functionand non-motor symptoms were rated by multiple scales. Dopamine, acetylcholine, norepinephrine and 5-hydroxytryptamine levels in cerebrospinal fluid (CSF) were measured. We found that thePD-OD group showed significantly lower score of Montreal Cognitive Assessment Scale, higher scores of rapid eye movement sleep behavior disorder (RBD) Screening Questionnaire and Epworth Sleepiness Scale than thePD-nOD group (p < 0.05). RBD Screening Questionnaire score was independently associated with the scores of overall olfactory function and discrimination (p < 0.05). Dopamine and acetylcholine levels in CSF from thePD-OD group was significantly lower than that from thePD-nOD group (p < 0.05). Dopamine and acetylcholine levels in CSF were significantly and positively correlated with the scores of overall olfactory function, threshold, discrimination and identification in PD patients (p < 0.05). RBD Screening Questionnaire score was significantly and negatively correlated with acetylcholine level in CSF in PD patients with poor olfactory detection (p < 0.05). This investigation reveals that PD-OD is associated with cognitive impairment, probable RBD and excessive daytime sleepiness. PD-OD is correlated with the decreased levels of dopamine and acetylcholine in CSF. RBD is an independent influencing factor of overall olfactory function and discrimination, and thedecreased acetylcholine level in CSF may be the common neurobiochemical basis of RBD and OD in PD patients.

Development and validation of a sample stabilization strategy and a UPLC–MS/MS method for the simultaneous quantitation of acetylcholine (ACh), histamine (HA), and its metabolites in rat cerebrospinal fluid (CSF)

A UPLC–MS/MS assay was developed and validated for simultaneous quantification of acetylcholine (ACh), histamine (HA), tele-methylhistamine (t-mHA), and tele-methylimidazolacetic acid (t-MIAA) in rat cerebrospinal fluid (CSF). The biological stability of ACh in rat CSF was investigated. Following fit-for-purpose validation, the method was applied to monitor the drug-induced changes in ACh, HA, t-mHA, and t-MIAA in rat CSF following administration of donepezil or prucalopride. The quantitative method utilizes hydrophilic interaction chromatography (HILIC) Core–Shell HPLC column technology and a UPLC system to achieve separation with detection by positive ESI LC–MS/MS. This UPLC–MS/MS method does not require extraction or derivatization, utilizes a stable isotopically labeled internal standard (IS) for each analyte, and allows for rapid throughput with a 4 min run time. Without an acetylcholinesterase (AChE) inhibitor present, ACh was found to have 1.9 ± 0.4 min in vitro half life in rat CSF. Stability studies and processing modification, including the use of AChE inhibitor eserine, extended this half life to more than 60 min. The UPLC–MS/MS method, including stabilization procedure, was validated over a linear concentration range of 0.025–5 ng/mL for ACh and 0.05–10 ng/mL for HA, t-mHA, and t-MIAA. The intra-run precision and accuracy for all analytes were 1.9–12.3% CV and −10.2 to 9.4% RE, respectively, while inter-run precision and accuracy were 4.0–16.0% CV and −5.3 to 13.4% RE, respectively. By using this developed and validated method, donepezil caused increases in ACh levels at 0.5, 1, 2, and 4 h post dose as compared to the corresponding vehicle group, while prucalopride produced approximately 1.6- and 3.1-fold increases in the concentrations of ACh and t-mHA at 1 h post dose, respectively, compared to the vehicle control. Overall, this methodology enables investigations into the use of CSF ACh and HA as biomarkers in the study of these neurotransmitter systems and related drug discovery efforts.

Facts, myths, and controversies in vascular dementia

Significant progress in the field of VaD resulted from publication of the NINIDS-AIREN Diagnostic Criteria for VaD (G.C. Román, T.K. Tatemichi, T. Erkinjuntti, et al., Vascular dementia (VaD): diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 43 (1993) 250–260). Epidemiological studies confirmed the importance of VaD as the second most common cause of dementia in the elderly, representing 15–20% of all cases of dementia. In Europe and North America, Alzheimer's disease (AD) predominates over VaD in a 2:1 ratio; in contrast, in Japan and China VaD accounts for almost 50% of all dementias. Case-control studies have identified risk factors for VaD including ageing, hypertension, diabetes mellitus, hyperlipidemia, recurrent stroke, cardiac disease, smoking, sleep apnea, and more recently, hyperhomocysteinemia, among others. Hypertension treatment may prevent VaD and AD. This finding has enormous importance from the Public Health viewpoint to decrease the future number of patients with dementia in the elderly. Along with advances in the field of VaD came a number of controversies and damaging misconceptions and myths. Myth no. 1—Vascular dementia is a non-entity: The false idea that VaD does not exist is particularly destructive because it creates the perspective that VaD is unworthy of study or research. A condition that either does not exist or represents only a minute proportion of all cases of dementia in the elderly, lacks public health relevance and becomes a low priority for research by funding agencies and industry. In fact, vascular brain lesions are the commonest and most important component of dementia in the elderly. Myth no. 2—Vascular dementia is so difficult to diagnose that only experts can recognize and identify it accurately: VaD does exist and the diagnosis of post-stroke VaD, in particular is straightforward. Most cases fulfill NINDS-AIREN criteria for probable VaD; i.e., (1) there is acute onset of dementia demonstrated by impairment of memory and two other cognitive domains, such as orientation, praxis or executive dysfunction; (2) relevant cerebrovascular lesions are demonstrated by neuroimaging; and (3) a temporal relation between stroke and cognitive loss is evident. In the donepezil trials on VaD, post-stroke dementia represented about 75% of the >1,200 patients enrolled. Myth no. 3—Improvement in clinical trials of cholinergics in VaD is due to underlying AD, not to the vascular lesions. Experimental, clinical and pathological evidence has demonstrated cholinesterase deficits in VaD (independently of any concomitant AD pathology), including low acetylcholine in cerebrospinal fluid, and reduced choline acetyltransferase (ChAT) in the brain.

Analgesic Doses of Intrathecal but Not Intravenous Clonidine Increase Acetylcholine in Cerebrospinal Fluid in Humans

Analgesic Doses of Intrathecal but Not Intravenous Clonidine Increase Acetylcholine in Cerebrospinal Fluid in Humans

Cerebrospinal Fluid Norepinephrine and Acetylcholine Concentrations During Acute Pain

Painful stimulation increases spinal cord norepinephrine (NE) in animals, and spinally released NE induces acetylcholine (ACh) release to cause analgesia. The purpose of this study was to determine the relationship between NE and ACh in cerebrospinal fluid (CSF) in sheep and humans during painful stimulation. CSF was sampled in anesthetized sheep before and during electrical nerve stimulation at an intensity sufficient to increase mean arterial pressure 15%-20%. To determine whether spinally released NE caused ACh release by stimulation of alpha(2)-adrenoceptors, seven sheep received intrathecal (IT) idazoxan whereas seven sheep received IT saline before stimulation. To examine the effect of pain on CSF NE and ACh in humans, CSF was sampled in 33 women after at least 4 h of painful labor and in 22 pregnant women without pain. Painful stimulation in sheep increased CSF NE and ACh. IT idazoxan blocked the increase in both NE and ACh. Although mean concentrations of CSF NE and ACh did not differ between parturients with and without pain, there was a significant correlation between NE and ACh concentrations only in those with pain. These data provide evidence in animals for activation of spinal cord noradrenergic-cholinergic systems in response to pain. There is only weak evidence for such activation, however, in women with painful labor.

Ultramicro determination of acetylcholine in cerebrospinal fluid.

Ultramicro determination of acetylcholine in cerebrospinal fluid.