Group Of Cholinergic Neurons Research Articles

OBESITY AND TYPE 3 DIABETES: NUTRITIONAL APPROACHES AND THERAPEUTIC IMPLICATION

Over nutrition induced diseases such as obesity and type 2 diabetes involve neural deregulation of metabolic physiology. Many findings describe the roles of over nutrition-associated hypothalamic inflammation in neurodegeneration and impaired adult neurogenesis as well as defective neural stem cell regeneration and their significance in obesity and related disease. Metabolic disorders include oxidative stress, insulin resistance, obesity and inflammation. Collectively, metabolic syndrome perturbs brain function and increases the incidence of neurodegenerative diseases, reflecting the possible involvement of obesity induced metabolic syndrome in development of Alzheimer's disease (AD) which is the most common form of dementia. Its key symptoms include progressive decline in the memory, impairment in speech, language, spatial orientation and dysfunction in the sensor motor system . Alzheimer's disease (AD) is a chronic neurodegenerative disease that usually start slowly and worsens over time. It is the cause of 60-70% of cases of dementia . Several mechanisms have been described to understand pathology of AD including damaging groups of cholinergic neurons with down regulation of cholinergic markers accumulation of amyloid beta peptide (Aβ) forming extracellular senile plaques, aggregation of hyperphosphorylated tau to form intracellular neurofibrillary tangles and oxidative stress .

Commissural fibers may guide cholinergic neuronal migration in developing rat cervical spinal cord.

The present investigation examines the role of intercellular relationships in the guidance of neuronal migration in embryonic rat cervical spinal cord. A "U-shaped" group of cholinergic neurons, was first detected on embryonic days (E) 15.5-16 surrounding the ventral proliferative zone. At these stages, no cholinergic cells were observed in the dorsal spinal cord, but by E17, many of the "U-shaped" group of cholinergic cells appeared to have translocated dorsally, to become the cholinergic dorsal horn cells seen in older animals. Between E16 and E17, these choline acetyltransferase (ChAT)-immunoreactive cells displayed primitive processes oriented dorsoventrally, suggesting migration along that axis. Two early forming substrates present in embryonic spinal cord have been implicated in the guidance of other populations of migrating neurons: glial cells organized in radial arrays and commissural axons aligned along the dorsoventral axis. Involvement of the commissural fibers with cholinergic cell migration seems more likely because the fibers and the translocation pathway have similar orientations. In double-labeling immunocytochemical studies of E15.5-17 spinal cord, some immature ChAT-containing neurons were directly adjacent to commissural fibers, as identified by SNAP/TAG-1 immunoreactivity. The temporal and spatial coincidence of developing cholinergic neurons and commissural axons is consistent with the hypothesis that these neurons could use commissural fibers as migratory guides. In addition, conventional electron micrographs were examined to determine if immature neuronal profiles were physically apposed to commissural axons. Immature neurons with leading and trailing processes oriented dorsally and ventrally, respectively, were embedded within and aligned along bundles of commissural fibers or along other similarly oriented neurons. This direct apposition of immature cells to the surfaces of commissural axons and other bipolar neurons is consistent with the hypothesis that the "U-shaped" group of cholinergic neurons may use commissural axons and other cohort neurons for guidance during their dorsal migration.

Nerve growth factor and Alzheimer's disease.

Nerve growth factor (NGF) is a well-characterized protein that exerts pharmacological effects on a group of cholinergic neurons known to atrophy in Alzheimer's disease (AD). Considerable evidence from animal studies suggests that NGF may be useful in reversing, halting, or at least slowing the progression of AD-related cholinergic basal forebrain atrophy, perhaps even attenuating the cognitive deficit associated with the disorder. However, many questions remain concerning the role of NGF in AD. Levels of the low-affinity receptor for NGF appear to be at least stable in AD basal forebrain, and the recent finding of AD-related increases in cortical NGF brings into question whether endogenous NGF levels are related to the observed cholinergic atrophy and whether additional NGF will be useful in treating this disorder. Evidence regarding the localization of NGF within the central nervous system and its presumed role in maintaining basal forebrain cholinergic neurons is summarized, followed by a synopsis of the relevant aspects of AD neuropathology. The available data regarding levels of NGF and its receptor in the AD brain, as well as potential roles for NGF in the pathogenesis and treatment of AD, are also reviewed. NGF and its low affinity receptor are abundantly present within the AD brain, although this does not rule out an NGF-related mechanism in the degeneration of basal forebrain neurons, nor does it eliminate the possibility that exogenous NGF may be successfully used to treat AD. Further studies of the degree and distribution of NGF within the human brain in normal aging and in AD, and of the possible relationship between target NGF levels and the status of basal forebrain neurons in vivo, are necessary before engaging in clinical trials.

Human reticular formation: Cholinergic neurons of the pedunculopontine and laterodorsal tegmental nuclei and some cytochemical comparisons to forebrain cholinergic neurons

Choline acetyltransferase immunohistochemistry showed that the human rostral brainstem contained cholinergic neurons in the oculomotor, trochlear, and parabigeminal nuclei as well as within the reticular formation. The cholinergic neurons of the reticular formation were the most numerous and formed two intersecting constellations. One of these, designated Ch5, reached its peak density within the compact pedunculopontine nucleus but also extended into the regions through which the superior cerebellar peduncle and central tegmental tract course. The second constellation, designated Ch6, was centered around the laterodorsal tegmental nucleus and spread into the central gray and medial longitudinal fasciculus. There was considerable transmitter-related heterogeneity within the regions containing Ch5 and Ch6. In particular, Ch6 neurons were intermingled with catecholaminergic neurons belonging to the locus coeruleus complex. The lack of confinement within specifiable cytoarchitectonic boundaries and the transmitter heterogeneity justified the transmitter-specific Ch5 and Ch6 nomenclature for these two groups of cholinergic neurons. The cholinergic neurons in the nucleus basalis (Ch4) and those of the Ch5-Ch6 complex were both characterized by perikaryal heteromorphism and isodendritic arborizations. In addition to choline acetyltransferase, the cell bodies in both complexes also had high levels of acetylcholinesterase activity and nonphosphorylated neurofilament protein. However, there were also marked differences in cytochemical signature. For example, the Ch5-Ch6 neurons had high levels of NADPHd activity, whereas Ch4 neurons did not. On the other hand, the Ch4 neurons had high levels of NGF receptor protein, whereas those of Ch5-Ch6 did not. On the basis of animal experiments, it can be assumed that the Ch5 and Ch6 neurons provide the major cholinergic innervation of the human thalamus and that they participate in the neural circuitry of the reticular activating, limbic, and perhaps also extrapyramidal systems.

Galanin-like immunoreactivity in cholinergic neurons of the septum-basal forebrain complex projecting to the hippocampus of the rat

It is now wel recognized that there are several groups of cholinergic neurons in the basal forebrain with direct projections to various cortical regions. Immunohistochemical investigations of the distribution of the neuropeptide galanin (GAL) have shown that two of these brain areas, the medial septum and diagonal band, contained large numbers of GAL-immunoreactive neurons. In the present study, double staining techniques using antibodies raised against choline acetyltransferase (ChAT) revealed that GAL- and ChAT- like immunoreactivities are colocalized within a subpopulation of the cholinergic neurons within the medial septum and diagonal band. This colocalization of GAL- and ChAT-immunoreactivities was not seen to occur within other groups of forebrain cholinergic neurons. Immunohistochemistry carried out subsequent to injections of fluorescent retrograde tracers into the hippocampal formation revealed that both ChAT/GAL- and ChAT-containing neurons project to the hippocampal formation. The question of GAL as a modulator of cholinergic transmission in this projection is discussed.

Innervation of the cultured fetal rat pancreas

The fetal rat pancreas, explanted at 18 days of gestation and cultured up to ten days, contains numerous acetylcholinesterase-positive neurons. These nerves usually appear in small ganglia although single nerve cells are encountered. The axons of these intrapancreatic nerves appear to terminate only in the islet tissue and not on any exocrine components of the explant. It is concluded that the fetal rat pancreas contains an islet-specific group of cholinergic neurons.