We have recently reported that inbred Wistar-Kyoto rats which are highly reactive to stressful stimuli, have a much shorter mean life-span (21.5) compared to the less reactive Brown-Norway rats (31.0 +/- 4.5 months). In the present study we found a reduction in forebrain cholinergic neurotransmission indices in 24-month-old Wistar-Kyotos but not in Brown-Norways as compared to their respective young (3-month-old) counterparts. Also only in Wistar-Kyotos dopamine uptake was reduced in the aged striatum, but in the septum it remained unchanged in both strains. In Brown-Norways, age-related changes were observed only in choline acetyltransferase activity and only in brain regions known to contain mainly cholinergic nerve cell bodies. We conclude that at 24 months of age, reductions in brain cholinergic and dopaminergic neurotransmission are more prominent in the highly stress-reactive and shorter-lived Wistar-Kyoto strain, and may be genetically determined.
Stress induced changes in neurochemical indices of neurotransmission are more pronounced in the septohippocampal cholinergic system of Wistar Kyoto rats, which are behaviorally more reactive to stressors and have a shorter life span, than in Brown Norway rats. Moreover, pronounced degeneration of septohippocampal cholinergic neurons occurs earlier in life in Wistar Kyoto rats. In the present study the high affinity synaptosomal uptakes of choline and glutamate were used as indices for cholinergic and glutamatergic systems respectively. Following 2 hr of mild restrain stress increases in both uptake systems were observed in all regions examined (hippocampus, septum and frontal cortex). The stress-induced increases were generally similar in young (3 months) and aged (20 months) rats of both strains. The noted exception was that choline uptake levels, which were reduced in the hippocampus of unhandled aged WKY rats, remained unchanged after stress. The results confirm the involvement of the septohippocampal cholinergic system in the response to acute stress and extend the findings to include the hippocamposeptal glutamatergic system activation as well. It is suggested that in spite of neuronal degeneration during aging, these responses to stress can be maintained by compensatory efforts of neurons that remain intact.
A comparative study was carried out in the properties of ATPase system of the skeletal muscle nuclei in the rabbits in norm and with experimental muscular dystrophy conditioned by E-avitaminosis. It is shown that in the system, containing 1.5 mM of MgCl2, ATPase system of the nuclei is activated by sodium and potassium ions. In norm maximum activation is observed with their presence in the medium, the concentration being 80 and 70 mM, respectively. With experimental muscular dystrophy maximum activating concentrations decrease and are equal for both cations - 30 mM. Activation of the enzymatic system by these ions is specific because the introduction of equimolar quantities of cholin-chloride or lithium, cesium ions instead of sodium ions into the incubation medium evokes no activation of the ATPase system of the rabbit skeletal muscles both in norm and with experimental muscular dystrophy. A simultaneous presence of sodium and potassium ions in optimum concentrations in the incubation medium makes for an increase of ATPase activity to the same extent as the presence of one of these cations. Oubain, a specific inhibitor of Mg2+, Na+, K+- ATPase, taken in the concentrations of 10(-4) and 10(-3) M did not decrease the intensity of ATP hydrolysis and its activation conditioned by the presence of sodium or potassium. A conclusion is made that Mg2+, Na+, K+-ATPase taking part in the work of "sodium pump" is absent in the nuclei of skeletal muscles.
We studied electrophysiological parameters and morphological changes in the adrenal glands and spleen of CBA mice feeding a low-choline diet and/or ethanol-containing diet. The polarization coefficient underwent similar changes in the adrenal glands and spleen, which was associated with different contribution of impedance frequency components. Morphological changes in the adrenal glands were more pronounced than in the spleen and consisted in delipidation of the adrenocortical cell cytoplasm in the zona fasciculata and increase in cell heterogeneity in the zona reticularis of animals of different groups. The observed morphological and electrophysiological changes can serve as a criterion of the severity of stress. The method for a quantitative study of tissue electroconductivity is informative for evaluation of the effects of internal and external factors on organs and tissues.
The content and specific activity of labelled methyl groups of choline and phosphorylcholine in the brain, liver and skeletal muscles of rats was studied as affected by nicotinic acid and prozerin, injected subcutaneously 4h before decapitation. It was found that under the effect of prozerin the specific activity of choline lowers only in the muscles and nicotinic acid evokes its decrease in the liver and muscles. The specific activity of phosphorylcholine lowers in the brain and liver with introduction of prozerin and nicotinic acid. The intensity of phosphorylcholine phosphate renewal increases in the liver and skeletal muscles after introduction of both prozerin and nicotinic acid. The activity of choline dehydrogenase in the liver homogenates lowers only with injection of nicotinic acid.
The content and incorporation intensity of tritium from methionine CH33-groups as well as ATP phosphorus renewal of the skeletal muscles, liver and brain were studied in albino rats as effected by proserin, nicotinic acid and the vagus cutting. It is established that the organs and tissues with a high metabolic activity of ATP are characterized by a higher level of its renewal of ATP. Proserin and the vagus cutting are most likely to affect the renewal of ATP through choline metabolism. Nicotinic acid may affect the renewal of ATP through pyridine nucleotides in the process of oxidative phosphorylation.
We aimed to test whether in vivo levels of magnetic resonance spectroscopy (MRS) metabolites myo-inositol (mI), N-acetylaspartate (NAA), and choline are abnormal already during preclinical Alzheimer disease (AD), relating these changes to amyloid or tau pathology, and functional connectivity.
In this cross-sectional multicenter study (a subset of the prospective Swedish BioFINDER study), we included 4 groups, representing the different stages of predementia AD: (1) cognitively healthy elderly with normal CSF ß-amyloid 42 (Aß42), (2) cognitively healthy elderly with abnormal CSF Aß42, (3) patients with subjective cognitive decline and abnormal CSF Aß42, (4) patients with mild cognitive decline and abnormal CSF Aß42 (Ntotal = 352). Spectroscopic markers measured in the posterior cingulate/precuneus were considered alongside known disease biomarkers: CSF Aß42, phosphorylated tau, total tau, [(18)F]-flutemetamol PET, f-MRI, and the genetic risk factor APOE.
Amyloid-positive cognitively healthy participants showed a significant increase in mI/creatine and mI/NAA levels compared to amyloid-negative healthy elderly (p
We present here a combination of time-domain signal analysis procedures for quantification of human brain in vivo 1H NMR spectroscopy (MRS) data. The method is based on a separate removal of a residual water resonance followed by a frequency-selective time-domain line-shape fitting analysis of metabolite signals. Calculation of absolute metabolite concentrations was based on the internal water concentration as a reference. The estimated average metabolite concentrations acquired from six regions of normal human brain with a single-voxel spin-echo technique for the N-acetylaspartate, creatine, and choline-containing compounds were 11.4 +/- 1.0, 6.5 +/- 0.5, and 1.7 +/- 0.2 mumol kg-1 wet weight, respectively. The time-domain analyses of in vivo 1H MRS data from different brain regions with their specific characteristics demonstrate a case in which the use of frequency-domain methods pose serious difficulties.