Neonatal lesions of catecholaminergic system prevents maturation of cholinergic innervation of the rat neocortex

The influence ofcatecholaminergic system on functioning of the somatosensory and cholinergic systems in early ontogenesis in rats was studied. The neonatal systemic administration of the neurotoxin 6-hydroxydopamine modifies sensitivity of neurons in the somatosensory cortex to peripheral stimulation (stimulation of the sciatic nerve). It is shown that in animals with lesions, catecholaminergic system reduces the number of the cortical neurons responsive to stimulation of ascending cholinergic pathways. The sensitivity of these neurons to acetylcholine does not change. The damage in the early ontogeny catecholaminergic mechanisms seems to prevent maturation of cholinergic afferents in the neocortex.     

Does the destruction of the catecholaminergic neurons in newborn rat pups influence the modulatory function of the cholinergic system?]

On outbred ratlings aged 21-31 days the influence was studied of the destruction of catecholaminergic (CA) system on the reactions of the neurones of the cortical somatosensory zone, elicited by the stimulation of the ischiatic nerve and modulation of these reactions after stimulation of the basal nuclei area (the source of the neocortex cholinergic innervation) and acetylcholine (ACh) microiontophoretic application. It is shown that destruction of CA system in newborn ratlings increases the reactivity of the somatosensory cortical neurones in 21-31 days old animals to sensory stimulation; it does not influence the efficiency of modulating action of the cholinergic system of the forebrain and leads to the increase of modulating influence of the applicated ACh. It is postulated that as the result of perinatal destruction of CA brain system, in the neocortex a specific morpho-functional organization is formed of structures and processes at which the modulating function of the forebrain cholinergic system turns out, by quantitative criterion, at least, to be compensated.     

Effects of cholinergic drugs on growth hormone release

Acetylcholine and the cholinergic agonists, pilocarpine and physostigmine, increased GH release $\text{in}$$\text{vivo}$. The increase in GH release by pilocarpine was reversed by concurrent administration of the cholinergic receptor blocker, atropine, whereas atropine alone did not alter serum GH concentrations. Cholinergic stimulation of GH release appears to be partially mediated through a catecholaminergic system since the response was partially inhibited by pimozide, a dopamine receptor blocker, or phentolamine, an α-adrenergic receptor blocker. The cholinergic system may function physiologically to help regulate GH release.     

Intrinsic Innervation of the Chicken Lower Digestive Tract

We have studied the different components of the enteric nervous system in the rectum and cloaca of the chicken by means of hystochemical and immunohistochemical techniques. We found cholinergic neuronal bodies as well as nervous fibers, which constitute part of the Meissner and Auerbach plexuses. We also observed plentiful catecholaminergic fibers in both plexuses, though there were no catecholaminergic neuronal bodies. With respect to the Vasoactive Intestinal Peptide (VIP) and substance P (SP) positive peptidergic innervation, only positive fibers were found, which were less abundant than in the other zones of the gastrointestinal tract. The optic microscopy results were confirmed by electron microscopy.     

Submucosal plexus of terminal ileum: a study of the cholinergic and noradrenergic nerves in rats with streptozotocin-induced diabetes.

In order to study the type and degree of the alterations in the innervation of the intestine in experimental diabetes, a histochemical study on the cholinergic and noradrenergic nerves of the submucosal plexus of terminal ileum from rats with streptozotocin-induced diabetes was performed. The results obtained suggest that the diabetic animals keep the cholinergic activity undamaged 20 weeks after the induction of the illness, while the number of the catecholaminergic nerves appears to be markedly reduced.     

Neurotransmitters and neuropeptides in the developing human central nervous system. A review

This is a review on the ontogenesis of major neurotransmitters and neuropeptides in the developing human central nervous system. In general, the molecules under study appeared early in development, usually in the first trimester. Cholinergic neurons were found to be present around the time of neuropeptide formation. The newly formed neuropeptidergic fibers extended towards the cholinergic centers where both might interact. In the major centers of the central nervous system, neuropeptides were also noted to colocalize with various neurotransmitters. For example, in the facial nucleus, enkepahlin and substance P fibers coexisted with cholinergic and catecholaminergic neurons, suggesting complex interactions. In the interpeduncular nucleus, peptidergic neurons acting as interneurons clearly modulated the afferent input to this nucleus. In the hippocampus and in sensory organs such as the retina, there were indications that neuropeptides and gamma-amino butyric acid coexisted. We hypothesize that interactions of neurotransmitters and peptides in neurons and fibers early in development play an indispensable role in the morphogenesis of the human central nervous system.     

Neuroendocrine effect of sex hormones

The paper provides a generalization of data and the results of own experiments on influence ovarian steroids on the hypothalamus and other brain areas related to reproduction. Ovarian hormones have widespread effects throughout the brain: on catecholaminergic neurons and serotonergic pathways and the basal forebrain cholinergic system, as well as the hipocampus, spinal cord, nigrostriatal and mesolimbic system, in addition to glial cells and blood-brain barrier. The widespread influences of these various neuronal systems ovarian steroids have measurable effects on mood and affect as well as on cognition, with implications for dementia. There are developmentally programmed sex differenced in hippocampal structure that may help to explain differences in the strategies which male and female rats use to solve spatial navigation problems. The multiple sites and mechanisms of estrogen action in brain underlie a variety of importants effects on cognitive and other brain functions--coordination of movement, pain, affective state, as well as possible protection in Alzheimer's disease. Estrogen withdrawal after natural or surgical menopause can lead to a host of changes in brain function and behavior.     

The effect of adren- and serotoninergic substances on the behavior of amygdalectomized rats and on the aggressiveness evoked by intra-amygdaloid administration of acetylcholine]

The effect of serotoninergic (serotonin, 1-trytophane, imipramime, methysergide), catecholaminergic (noradrenaline, amphetamine, dopamine, 1-DOPA, iproniazid) and cholinergic drugs (physostigmine, atropine, benactyzine) on emotional reactions and orienting-motor activity, as well as the effect of these drugs on shock-elicited aggressiveness enhanced by intraamygdaloid microinjection of acetylcholine was investigated in experiments on amygdalectomized male albino rats. In amygdalectomized animals, as compared to control false-operated rats, the stimulating effect of amphetamine, imipramine, tryptophane and m-cholinoblockators was enhanced and their inhibitory effect was weakened. Bilateral microinjection of cholinergic drugs (acetylcholine, physostigmine and carbacholine) and noradrenaline into the amygdaloid body intensified emotional reactivity and aggressiveness. Microinjection of serotonin and dopamine inhibited aggressiveness and caused facilitaion of orienting-motor activity. It is suggested that the adrenergic system intensifies and serotoninergic system depresses the m-cholinergic trigger mechanism of aggressive behavior in limbico-diencephalic structures.     

The effects of opiate agonists on growth hormone and prolactin release in rats

Various opioid receptor agonists, including Met5-enkephalin amide, Leu5-enkephalin amide, [D-Ala]2-Met5-enkephalin amide, [D-Ala]2-Leu5-enkephalin amide, morphine sulfate, d-methadone hydrochloride, and l-methadone hydrochloride were administered to adult male rats by subcutaneous injection. All opioid receptor agonists except Leu5-enkephalin amide significantly stimulated growth hormone and prolactin release. Naloxone and naltrexone blocked the hormone stimulatory effects of the opioids and both naloxone and naltrexone, when administered alone, significantly reduced serum growth hormone and prolactin concentrations. The dopaminergic agonist apomorphine, but not the alpha-adrenergic agonist clonidine, blocked opiate stimulation of prolactin. Morphine sulfate caused growth hormone release in rats pretreated with alpha-methyl-p-tryosine, a catecholamine synthesis inhibitor. Cholinergic agonists, physostigmine and pilocarpine, antagonized the growth hormone and prolactin release induced by morphine sulfate. The data suggest that the opiates stimulate prolactin via an interaction with catecholaminergic neurons controlling prolactin release and stimulate growth hormone via a mechanism independent of alpha-adrenergic or general catecholaminergic influence. The mechanism through which cholinergic agonists act to inhibit opiate agonist stimulation of growth hormone is presently unknown.     

Cholinergic and catecholaminergic neurons relay striatal information to the optic tectum in amphibians.

In the amphibians Rana perezi and Xenopus laevis, the involvement of cholinergic and catecholaminergic neurons in the relay of basal ganglia inputs to the tectum was investigated. Tract-tracing experiments, in which anterograde tracers were applied to the basal ganglia and retrograde tracers to the optic tectum, were combined with immunohistochemistry for choline acetyltransferase and tyrosine hydroxylase. The results of these experiments suggest that dopaminergic neurons of the suprachiasmatic nucleus and pretectal region, noradrenergic cells of the locus coeruleus and the cholinergic neurons of the pedunculopontine and laterodorsal tegmental nuclei mediate at least part of the basal ganglia input to the tectum in anurans.     

Architectonics of the central nervous system of Acoela,Platyhelminthes, and Rotifera

Based on the literature and own data, consecutive stages of development of the central nervous system (CNS) in the lower Bilateria are considered-separation of brain from parenchyma, formation of its own envelopes, and development of the trunk and orthogonal nervous system. Results of histochemical (cholinergic and catecholaminergic) and immunocytochemical (5-HT-and FMRF-amid immunoreactive) studies of the CNS in representatives of Acoela, free living and parasitizing Platyhelminthes and Rotifera are considered. The comparative analysis makes it possible to describe development and complication of the initially primitive Bilateria pleux nervous system. A special attention will be paid to the Acoela phylogenesis, based on molecular-biology data and results of study of their nervous system.     

Brainstem in Multiple System Atrophy: Clinicopathological Correlations

1. Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that manifests with parkinsonism, cerebellar ataxia, and autonomic failure in various combinations.2. Orthostatic hypotension, neurogenic bladder, laryngeal stridor and sleep apnea, and rapid eye movement (REM) sleep behavior disorder are prominent manifestations of MSA.3. In MSA, there is severe depletion of catecholaminergic neurons of the C1 and A1 areas in the ventrolateral medulla, and this may contribute to orthostatic hypotension and endocrine disturbances in this disorder, respectively.4. Loss of corticotrophin-releasing factor (CRF) neurons in the pontine micturition area may contribute to neurogenic bladder dysfunction.5. Respiratory abnormalities may reflect loss of cholinergic neurons in the arcuate nucleus of the ventral medulla.6. Loss of cholinergic mesopontine neurons, in the setting of loss of locus ceruleus neurons and preservation of rostral raphe neurons, may contribute to REM sleep abnormalities in MSA.     

Architectonics of the central nervous system in Acoela, Plathelminthes, and Rotifera

Based on the literature and own data, consecutive stages of development of the central nervous system (CNS) in the lower Bilateria are considered - separation of brain from parenchyma, formation of its own envelopes, and development of the stem and orthogonal nervous system. Results of histochemical (cholinergic and catecholaminergic) and immunocytochemical (5-HT- and FMRFamid immunoreactive) studies of the CNS in representatives of Acoela, free living and parasitizing Plathelminthes and Rotifera are considered. The comparative analysis makes it possible to describe development and complication of the initially primitive Bilateria plexus nervous system. A special attention will be paid to the Acoela phylogenesis, based on molecular-biology data and results of study of their nervous system.     

The head-eye-body turning behavior induced by electrical or cholinergic stimulation of the pulvinar-lateralis posterior nucleus complex is not dependent on the catecholaminergic system

Two experimental designs were developed in cats in order to analyze the role of the catecholaminergic system in the turning response evoked by cholinergic or electrical stimulation of the pulvinar-lateralis posterior nucleus complex (P-LP). Twenty one adult cats were employed. In one series of experiments, nine cats had a cannula implanted in one P-LP, and through it, apomorphine alone or mixed with carbachol were microinjected. The behavior was observed and the EEG was recorded. In the second experimental design, a cannula and bipolar electrodes were implanted unilaterally in the P-LP of nine cats, and a series of electrical stimulations were performed before and after 6-OHDA administration into the P-LP, and apomorphine was injected parenterally in order to induce turning behavior. Finally three cats received 16 micrograms of 6 OHDA into the P-LP, through a Hamilton syringe and no electrodes or cannula were implanted, to study the histological damage. No evidence of involvement of the catecholaminergic system was found in either of these two experimental series. These results contrast with what has been found in the nigrostriatal dopaminergic system, where an imbalance in dopamine concentration induces turning behavior. High doses (16 micrograms) of 6-OHDA induced minimal damage in the P-LP.     

Characterization of a target-derived neuronal cholinergic differentiation factor

The sympathetic innervation of rat sweat glands undergoes a target-induced switch from a noradrenergic to a cholinergic and peptidergic phenotype during development. Treatment of cultured sympathetic neurons with sweat gland extracts mimics many of the changes seen in vivo. Extracts induce choline acetyltransferase activity and vasoactive intestinal peptide expression in the neurons in a dose-dependent fashion while reducing catecholaminergic properties and neuropeptide Y. The cholinergic differentiation activity appears in developing glands of postnatal day 5 rats and is maintained in adult glands. It is a heat-labile, trypsin-sensitive, acidic protein that does not bind to heparin-agarose. Immunoprecipitation experiments with an antiserum directed against an N-terminal peptide of a cholinergic differentiation factor (CDF/LIF) from heart cells suggest that the sweat gland differentiation factor is not CDF/LIF. The sweat gland activity is a likely candidate for mediating the target-directed change in sympathetic neurotransmitter function observed in vivo.     

Hemicholinium mustard derivatives: Preliminary assesment of cholinergic neurotoxicity

We have attempted to design novel neurotoxins based on the use of hemicholinium derivatives. Three compounds were tested for their neurochemical effects on cholinergic, gabaergic and catecholaminergic markers in the hippocampus, striatum and cortex following intracerebroventricular administration. The effects were compared with those of the non-specific alkylating agent (nitrogen mustard) and the previously reported ethylcholine mustard aziridinium ion (AF 64A). The results indicate that only one of these derivatives (HcM-9) exhibits comparable neurotoxic effects on cholinergic markers with a similar pattern of specificity to that of AF 64A. In addition, HcM-9 showed less overall toxicity, this being reflected in a higher survival rate. The present results indicate that hemicholinium derivatives could be good substrates for further molecular modifications, thus a step towards the design of a more specific cholinergic neurotoxin.Special Issue dedicated to Prof. Eduardo De Robertis.     

Influence of atropine and carbachol on the fluorescence of catecholaminergic structures in selected areas of the rat brain.

Using the formaldehyde-fluorescence technique, the authors studied the influence of atropine and carbachol, administered intraventricularly to Wistar rats, on the fluorescence of catecholaminergic structures in 20 areas of the CNS, situated within the range of the 10th-46th frontal plane according to KONIG and KLIPPEL. 1. A confirmation of the antagonistic action of atropine and carbachol was obtained. It was expressed by mutually opposed occurrence of the specific fluorescence of the catecholaminergic structures. 2. In 16 out of 20 studied areas of the CNS, carbachol abolished or considerably weakened the specific fluorescence. In 3 areas it was increased by this drug, and one area proved insensitive. 3. Atropine increased the specific fluorescence in the DA (dopaminergic system) areas, while it had varying effects in the NA (noradrenergic system areas. In some areas of the CNS it increased and in others reduced the specific fluorescence of the catecholaminergic structures. 4. An interference between atropine and carbachol is observed, but it seems that the results of the present experiment speak in favour of an interaction between the catecholamine transmitters and ACh in the particular areas of the CNS under the influence of atropine and carbachol. 5. The authors discuss in detail the reactions of the catecholaminergic structures in the particular areas of the CNS, in which, as compared with the control, an increase or a decrease of the specific fluorescence under the influence of the administered drugs was observed.     

The vegetative network in the guinea pig and rat sacral spinal cords

The intermediate zones in the sacral segments of guinea pig and rat spinal cords are histochemically investigated for the presence of catecholaminergic and cholinergic structures. The presence of a well-developed noradrenergic network is demonstrated. This network connects the preganglionic vegetative nuclei in horizontal and vertical directions. In addition, only some fibers from the bundles composing this network show acetylcholinesterase activity.     

The vegetative network in the guinea pig and rat sacral spinal cords

Summary The intermediate zones in the sacral segments of guinea pig and rat spinal cords are histochemically investigated for the presence of catecholaminergic and cholinergic structures. The presence of a well-developed noradrenergic network is demonstrated. This network connects the preganglionic vegetative nuclei in horizontal and vertical directions. In addition, only some fibers from the bundles composing this network show acetylcholinesterase activity.