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PubMed1990

Urethral function after chronic cauda equina lesions in cats. I. The contribution of mechanical factors and sympathetic innervation to proximal sphincter dysfunction.

We investigated the contribution of mechanical and sympathetic neural factors to proximal urethral sphincter dysfunction in the cat after chronic sacral rhizotomy. Concomitant vesicostomy prevented a decrease in the urethral pressure profile measured three months post-rhizotomy. Sympathetic influences on basal urethral perfusion pressure were the same in neurally-intact and chronic rhizotomised cats. A significant prazosin-sensitive component of basal urethral perfusion pressure remained after section of all extrinsic urethral innervation in both neurally-intact and chronic cats. Local intra-arterial 6-hydroxydopamine also abolished this component. After rhizotomy, noradrenaline content in the proximal urethra was significantly increased but there was no change in sensitivity to sympathetic stimulation. A small (5% of control) atropine-sensitive and prazosin-resistant constriction was seen only after chronic sacral rhizotomy. We conclude that a mechanical factor associated with bladder expression and not an alteration in sympathetic control is the major factor leading to diminished proximal urethral closure after vesicourethral lower motor neuron lesion. Furthermore, short adrenergic neurons have an important role in the maintenance of urethral pressure in the normal state and after lower motor neuron lesion.

Animals↗

PubMed2002

Impairment of cerebral cAMP-mediated signal transduction system and of spatial memory function after microsphere embolism in rats.

The transcription factor cAMP-responsive element binding protein (CREB) has been implicated in synaptic plasticity and memory. The purpose of the present study was to characterize alterations in the cAMP/protein kinase A (PKA)/CREB system after sustained cerebral ischemia. Sustained cerebral ischemia was induced by injection of 900 microspheres (48 microm in diameter) into the right (ipsilateral) hemisphere of rats. Alterations in the CREB, PKA, and cAMP levels in the cerebral cortex and hippocampus were examined up to 7 days after microsphere embolism. Immunoblotting analysis showed a decrease in the immunoreactivity of phosphorylated CREB (pCREB) in the ipsilateral hemisphere on the third day after microsphere embolism, whereas that of the total CREB was not altered. An electrophoretic gel mobility shift assay showed a decrease in the cAMP response element (CRE)-DNA binding activity of CREB in the ischemic region on the third day after the microsphere embolism. Cytosolic PKA C beta in the ipsilateral hemisphere was selectively decreased on the first day after the microsphere embolism, whereas the levels of another catalytic subunit, C alpha, and a regulatory subunit, RII alpha, were not altered. Immunoreactivity of the PKA catalytic subunit C alpha in the nucleus of the ipsilateral hemisphere was decreased on the third day after the embolism. The decreases in the pCREB, CRE-DNA binding activity, and PKA C alpha and C beta levels lasted at least up to 7 days after the operation. A decrease in the cAMP content was also seen in the ipsilateral hemisphere throughout the experiment. Furthermore, microsphere embolized rats showed prolongation of the escape latency in the water maze task determined on the seventh to ninth day after the operation. Our results suggest that sustained cerebral ischemia may impair the phosphorylation and CRE-DNA binding activity of CREB and that these effects may be one of the possible causes for learning and memory dysfunction.

Animals↗

PubMed2002

Estrogen replacement improves spatial reference memory and increases hippocampal synaptophysin in aged female mice.

Estrogen deficiency during menopause is often associated with memory dysfunction. However, inconsistencies regarding the ability of estrogen to improve memory in menopausal women highlight the need to evaluate, in a controlled animal model, the potential for estrogen to alleviate age-related mnemonic decline. The current study tested whether estrogen could ameliorate spatial reference memory decline in aged female mice. At the conclusion of testing, levels of the presynaptic protein synaptophysin, and activities of the synthetic enzymes for acetylcholine and GABA, were measured in the hippocampus and neocortex. Aged (27-28-month-old) female C57BL/6 mice were given daily subcutaneous injections of 1 microg or 5 microg of beta-estradiol-3-benzoate dissolved in sesame oil. Control mice received daily injections of sesame oil or no injections. Estradiol treatment began 5 days prior to behavioral testing and continued throughout testing. Spatial and non-spatial memory were assessed in the Morris water maze. The 5 microg dose of estradiol significantly improved spatial learning and memory in aged females. The performance of 5 microg females improved significantly more rapidly than that of control females; estradiol-treated females performed at asymptotic levels by session 2. Furthermore, 5 microg females exhibited a more robust spatial bias than controls during probe trials. In contrast, 1 microg of estradiol did not improve spatial task performance. Neither dose affected performance of the non-spatial task. In the hippocampus, synaptophysin was increased in 5 microg females relative to controls. Estrogen did not affect enzyme activities in either brain region. This study is the first to examine the effects of estrogen replacement on spatial reference memory and synaptophysin expression in aged post-estropausal female rodents. The results suggest that: (1) estrogen can profoundly improve spatial reference memory in aged females, and (2) this improvement may be related to increased hippocampal synaptic plasticity, but not modulation of the synthetic enzymes for acetylcholine and GABA.

Aging↗

PubMed1991

Postsynaptic neuromuscular dysfunction in organophosphate induced intermediate syndrome.

A 65-year-old Caucasian female developed an intermediate syndrome seven days after an acute cholinergic crisis, caused by the ingestion of fenthion. Cholinesterase activity in the blood, plasma and red cells was monitored daily by the method according to Nenner and serial serum fenthion levels were measured by capillary gas chromatography. Electromyographic studies showed fade on tetanic stimulation by means of surface electrodes at 20 Hz of the left M. abductor digiti quinti at day 7, which could no longer be observed at day 19. Fade on low-frequency stimulation and post-tetanic facilitation were both absent. A biopsy of the N. suralis was normal. A biopsy of the M. tibialis anterior revealed a limited rhabdomyolysis with a very weak staining for cholinesterase. It is hypothesized that the pathophysiologic process underlying the syndrome is the result of a time-confined phenomenon, which includes both changes in the postsynaptic structures by a desensitization process and a gradually restoring ratio of acetylcholine to acetylcholinesterase. This hypothesis is suggested by the similarity in the EMG-findings of this patient and those in myasthenia gravis, which is known to be characterized by a postsynaptic transmission defect.

Acetylcholinesterase↗

PubMed2003

[Regulation of psychomotor functions by dopamine: integration of various approaches].

(1)The basal ganglia circuitry mediates a wide rage of brain functions such as motor control, behavioral planning, and reward prediction. Dopamine (DA) transmission plays an essential role in the regulation of these brain functions. DA action not only regulates the firing activity of target neurons but also is involved in the pattern formation of their firing. The striatopallidal neurons containing dopamine D(2) receptor plays a dual role in motor coordination dependent on DA transmission. (2)Activation of presynaptic D(2)-like receptors on GABAergic terminals onto striatal cholinergic interneurons selectively blocks N-type Ca(2+) channels, thereby inhibiting GABA release. In addition, contribution of N-type channels and D(2)-like receptor-mediated presynaptic inhibition decreases in parallel with development, implying some relationship between basal ganglia-related function or dysfunction and age. (3)As an approach to determine dopamine neuronal activity, we monitored neuronal activities by measuring cytosolic Ca(2+) concentration in VTA dopamine neurons. The present study indicates that VTA dopamine neurons are the direct targets of orexin-A and psychostimulants, and the [Ca(2+)](i) signaling is thought to play a significant role in the regulation of dopamine neuronal activity. (4)The excitability of neostriatal neurons is regulated by a balance of glutamatergic and dopaminergic inputs. Glutamate has been shown to modulate dopaminergic signaling. Studies on the regulation of DARPP-32 phosphorylation by glutamate provide a molecular basis for both the synergistic and antagonistic effects of glutamate on dopaminergic signaling. (5) Impairment of function of stem/progenitor cells may be implicated in the pathogenesis of schizophrenia. To test this hypothesis, several experiments are currently ongoing in our laboratory, and the preliminary results obtained are described here.

Animals↗

PubMed1990

Pre- and postsynaptic adrenergic dysfunctions in hypertension.

Numerous experimental and clinical studies, using various approaches to evaluate the release of sympathetic transmitters and to obtain sympathetic nerve microneurographic recordings, have shown clearly that sympathetic system activity and reactivity is increased in experimental models of hypertension [deoxycorticosterone acetate (DOCA) salt and spontaneously hypertensive rats (SHR)] and in an important subgroup of essential hypertensive patients. This finding may reflect dysfunctions in the baroreflex blood pressure regulation, since an elevated blood pressure should normally inhibit sympathetic activity. This abnormality may arise from a variety of dysfunctions occurring at various sites along the baroreflex arc, including presynaptic modulatory adrenergic autoreceptors, where reduced sensitivity of presynaptic alpha 2 inhibitory receptors and enhanced sensitivity of beta 2 presynaptic receptors have been demonstrated. Although it has been possible to correlate the blood pressure elevation with various indices of sympathetic activity in experimental and human hypertension, the functional implications of that abnormality can be fully understood only in the light of concomitant alterations occurring in postsynaptic mechanisms. Pharmacologic, physiologic and biochemical studies strongly suggest that postsynaptic alpha 1 adrenergic functions become dominant while beta adrenergic functions are attenuated in hypertension. In experimental hypertension, this phenomenon is associated with a reduction in the number of beta adrenoceptors and in the production of its second messenger, cyclic AMP, whereas the number of alpha 1 adrenoceptors remained unchanged or increased, but the production of their second messengers, inositol triphosphate and diacylglycerol, is enhanced in cardiac and vascular tissues. These observations suggest the presence of an imbalance in postsynaptic adrenoceptor functions, which promotes the pressor effects of the sympathetic system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1997

Antipsychotic regulation of hippocampal dopamine receptor messenger RNA expression.

Medial temporal lobe structures including the hippocampus and entorhinal cortex have been implicated in the pathophysiology of schizophrenia. Markers of dopaminergic neurotransmission indicate that these regions receive dopaminergic innervation. Accordingly, dysfunction of dopaminergic neurotransmission within the hippocampus and associated cortical areas may be associated with schizophrenia. Little is known, however, about the expression and regulation of dopamine receptors in these regions. We determined the effects of 14 days of clozapine or haloperidol treatment on dopamine receptor messenger RNA (mRNA) expression in medial temporal regions of the rat brain by in situ hybridization. These two drugs had different effects in the hippocampus and entorhinal cortex, particularly a dissociation of their effects on D2 and D3 receptor mRNA expression. There was a parallel down-regulation of D4 mRNA by both drugs. D1 and D5 transcripts were not regulated by either treatment. These results suggest a differential pattern of regulation of D2-like receptor expression by clozapine and haloperidol in some medial temporal lobe structures. These drugs also appear to cause changes in the expression of these transcripts that differ from what has been reported in the striatum, adding to a growing literature suggesting that hippocampal and striatal dopamine receptors are differentially regulated.

Animals↗

PubMed1996

Biochemical markers of neurotoxicity. A review of mechanistic studies and applications.

Neurotoxicology presents major challenges to the development of biological markers in accordance to conventional research strategies. Because of the inaccessibility of the nervous system, one of the proposed alternatives is the study of biochemical signals in peripheral tissues which can easily and ethically be obtained in humans, and which could represent surrogate indicators of equivalent parameters in the nervous tissue. Considerable scientific support to this approach is provided by the results of recent investigations in major areas of pharmacology and psychobiology. Studies examining parameters of neurotransmission and second messenger systems in peripheral blood cells, and variations in the peripheral body fluid content of endogenous substances reflecting nervous tissue dysfunction or damage are presented in this paper as examples of efforts toward rational development and validation of novel indicators of nervous system toxicity. Cholinergic muscarinic receptors and calcium signalling in peripheral blood lymphocytes, myelin basic protein in cerebrospinal fluid, and blood polyamines are discussed as potential surrogate indicators based on the results of in vitro or in vivo animal studies of neurotoxic metals (mercury, triethyltin), pesticides (disulfoton), drugs of abuse (d-fenfluramine) and model epileptogenic compounds (kainic acid). Data from investigations examining serum prolactin, type B monoamine oxidase (MAO-B) and dopamine beta-hydroxylase (DBH) in workers occupationally exposed to manganese, lead or styrene are also presented. Although research in this field is still at its very early stage, current evidence suggests that (i) certain neurochemical markers may be valuably used in animal studies as a complement to conventional laboratory tests to augment their sensitivity or predictivity; (ii) a mechanistic research approach is required to establish which markers offer the greatest promise for application in human biomonitoring.

Animals↗

PubMed2003

Evidence for disturbed cortical signal processing and altered serotonergic neurotransmission in generalized anxiety disorder.

BACKGROUND: Current pathophysiological concepts of generalized anxiety disorder (GAD) assume a disturbed exteroceptive sensory system. Furthermore, central serotonergic neurotransmission has been shown to play an important role in anxiety disorder. Cortical signal processing as measured by auditory evoked potentials (AEPs) may reflect the integrity of the exteroceptive sensory system. Because a special aspect of AEP, the loudness dependence of the N1/P2-component (LD), has been related to central serotonergic activity, the LD may be useful for investigating serotonergic dysfunctions in GAD. METHODS: The LD was recorded in 31 medication-free patients with GAD without any psychiatric co-morbidity and in 31 matched control subjects. Dipole source analysis was performed to separate the LD of regions including the primary (LD-tangential dipole) and regions including the secondary auditory cortex (LD-radial dipole). RESULTS: A shallower LD-tangential was observed in patients with GAD as compared to healthy control subjects [F(1,60) = 6.727, p =.012; one-way analysis of variance]. The LD-radial showed no differences between groups. Severity of the anxiety symptoms was not related to the LDs. CONCLUSIONS: The results indicate an altered exteroceptive sensory system in GAD occurring at the level of the primary but not secondary auditory cortex. Because a shallow LD of the primary auditory cortex was related to a high firing rate of neurons in the dorsal raphe nucleus, the results may support evidence for an enhanced serotonergic activity in GAD.

Acoustic Stimulation↗

PubMed2004

[Diagnostics and conservative treatment of anal incontinence].

Anal incontinence is diagnosed primarily by clinical and proctologic examination. Etiological factors of the disease are found in 85% of the patients by additional examinations. Motility dysfunction of colon and rectum has to be excluded (stenosis, dyschezia, internal hernias). Because anal incontinence is a multifactorial disease as a rule, the single compounds have to be diagnosed and have to undergo therapy. Accordingly, useful investigations are: endorectal ultrasound (defect of muscle, inflammatory or tumour infiltration), manometry (alteration of either anal resting pressure and/or anal squeezing pressure) and surface electromyography (ability of contraction, duration of contraction, strength). Neurophysiological examinations are: needle electromyography, pudendal nerve latency time measurement (PNLT). The occurrence of nerve damage determines the outcome of operative intervention! Conservative treatment is indicated in 80 to 90% of all patients, even higher when one includes all patients in the perioperative period. Possible therapy modalities are: nutrition consultation, physiotherapy, pelvic floor training, biofeedback training of pelvic floor and sphincter muscles, electrostimulation and the combination of both (EMG-triggered electrostimulation). Short-term results are satisfying in up to 85% of patients, but later, successful results depend on the patient's willingness or ability to continue training, and on his/her age.

Anal Canal↗

PubMed1996

[Prolonged use of moxisylyte chlorhydrate (Icavex) by intracavernous self-injections in the treatment of impotence. Evaluation of long-term tolerance].

Moxisylyte chlorhydrate is a selective alpha-blocker of the post-synaptic alpha 1-adrenoreceptors. It has been used since 1992 for self-injections to induce erection. Tolerance has been studied in open trials in 143 men using 20 mg per intracavernous injection. Among these subjects, 104 were followed for 11 months. Self-administration was performed 7,509 times, i.e. 49.1 injections per subject over a mean period of 307 days. No severe side effects were observed. A total of 1,041 undesirable effects were reported by 90 subjects (75.1%), including mechanical disorders (28.2%) such as pain and burning sensation at injection, hematomas and ecchymoses. Nodules developed in 0.08% of these cases but always regressed. In 71.8% of the cases, the undesirable events was imputable to moxisylyte: dry mouth (2.73%), somnolence (1.9%), sinus congestion (0.71%). No case of priapism was reported. Long-term evaluation showed a reduction in the main undesirable effects with time. This fall off in the mechanical events could be explained by the subjects become for familiar with the technique. Pharmacological effects remain to be analysed. Added to the good tolerance, this result suggests that self-injection can be proposed as a first intention treatment for impotency.

Adrenergic alpha-Antagonists↗

PubMed2004

Antipsychotic drugs influence transport of the beta-adrenergic antagonist [3H]-dihydroalprenolol into neuronal and blood cells.

The amine hypothesis suggests that the cause of schizophrenic or depressive psychosis is dysfunction of noradrenergic or serotonergic neurotransmission. We investigated pharmacological properties of [3H]-dihydroalprenolol (DHA) transport into C6, IMR32, native lymphocytes, B-lymphoblastoids and MOLT-3 cells. DHA transport was inhibited by a heterogeneous group of structurally related compounds exhibiting an amine group and various aromatic ring structures. It was verified on cells of neuronal/glial and blood cell origin but in detail on B-lymphoblastoids. The latter once showed strongest inhibition of DHA transport using tricyclic antidepressants (amitriptyline: IC50 = 2.86 microM, imipramine: IC50 = 3.33 microM) and haloperidol (IC50 = 3.98 microM) as a neuroleptic. Antipsychotics like clozapine (IC50 = 11 microM), olanzapine (IC50 = 15 microM), spiperone (IC50 = 66 microM) and EMD 49980 (ICso >> 100 microM) were less effective. In contrast to cells of blood origin, a stimulation of DHA transport by antipsychotics was not detectable using neuronal cells. As antipsychotics showed a distinct inhibition and, concerning cells of blood origin, a stimulation of transport after pre-incubation, further investigations seem to be of interest in respect to its involvement in the cellular uptake of drugs and therefore its impact on the quality of therapy of psychiatric patients.

Adrenergic beta-Antagonists↗

PubMed2003

Affective disorders, antidepressant drugs and brain metabolism.

There is increasing evidence that affective disorders are associated with dysfunction of neurotransmitter postsynaptic transduction pathways and that chronic treatment with clinically active drugs results in adaptive modification of these pathways. Despite the close dependence of signal transduction on adenosine triphosphate (ATP) availability, the changes in energy metabolism in affective disorders are largely unknown. This question has been indirectly dealt with through functional imaging studies (PET, SPECT, MRS). Despite some inconsistencies, PET and SPECT studies suggest low activity in cortical (especially frontal) regions in depressed patients, both unipolar and bipolar, and normal or increased activity in the manic pole. Preliminary MRS studies indicate some alterations in brain metabolism, with reduced creatine phosphate and ATP levels in the brain of patients with affective disorders. However, the involvement of the energy metabolism in affective disorders is still debated. We propose direct neurochemical investigations on mitochondrial functional parameters of energy transduction, such as the activities of (a) the enzymatic systems of oxidative metabolic cycle (Kreb's cycle); (b) the electron transfer chain; (c) oxidative phosphorylation, and (d) the enzyme activities of ATP-requiring ATPases. These processes should be studied in affective disorders and in animals treated with antidepressant drugs or lithium.

Adaptation, Physiological↗

PubMed2001

Influence of postweaning social isolation in the rat on brain development, conditioned behaviour and neurotransmission.

There is substantial evidence that early life events influence brain development and subsequent adult behaviour and play an important role in the causation of certain psychiatric disorders including schizophrenia and depression. The underlying mechanism of the effects of these early environmental factors is still not understood. It is a challenge to attempt to model early environmental factors in animals to gain understanding of the basic mechanisms that underlie the long-term effects. This paper reviews the effects of rearing rats from weaning in social isolation and reports some recent results indicating hippocampal dysfunction. Isolation rearing in rats from weaning produces a range of persistent behavioural changes in the young adult, including hyperactivity in response to novelty and amphetamine and altered responses to conditioning. These are associated with alterations in the central aminergic neurotransmitter functions in the mesolimbic areas and other brain regions. Isolation-reared rats have enhanced presynaptic dopamine (DA) and 5-HT function in the nucleus accimbens (NAC) associated with decreased presynaptic 5-HT function in the frontal cortex and hippocampus. Isolation-reared rats have reduced presynaptic noradrenergic function in the hippocampus, but have enhanced presynaptic DA function in the amygdala. These neurochemical imbalances may contribute to the exaggerated response of the isolated rat to a novel stimulus or to stimuli predictive of danger, and isolation-induced behavioural changes. These changes have neuroanatomical correlates; changes which seem to parallel to a certain degree those seen in human schizophrenia. A greater understanding of the processes that underlie these changes should improve our knowledge of how environmental events may alter brain development and function, and play a role in the development of neuropsychiatric disorders.

Animals↗

PubMed2006

Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation.

Mutations or duplications in MECP2 cause Rett and Rett-like syndromes, neurodevelopmental disorders characterized by mental retardation, motor dysfunction, and autistic behaviors. MeCP2 is expressed in many mammalian tissues and functions as a global repressor of transcription; however, the molecular mechanisms by which MeCP2 dysfunction leads to the neural-specific phenotypes of RTT remain poorly understood. Here, we show that neuronal activity and subsequent calcium influx trigger the de novo phosphorylation of MeCP2 at serine 421 (S421) by a CaMKII-dependent mechanism. MeCP2 S421 phosphorylation is induced selectively in the brain in response to physiological stimuli. Significantly, we find that S421 phosphorylation controls the ability of MeCP2 to regulate dendritic patterning, spine morphogenesis, and the activity-dependent induction of Bdnf transcription. These findings suggest that, by triggering MeCP2 phosphorylation, neuronal activity regulates a program of gene expression that mediates nervous system maturation and that disruption of this process in individuals with mutations in MeCP2 may underlie the neural-specific pathology of RTT.

Animals↗

PubMed2006

Mechanisms underlying the long-term behavioral effects of traumatic experience in rats: the role of serotonin/noradrenaline balance and NMDA receptors.

Traumatic stressors induce long-lasting changes in behavior. It is believed that all three glutamatergic, serotonergic and noradrenergic neurotransmission play a role in the development of such behavioral changes, but their relative importance and relationship is poorly understood. We have shown previously that a single exposure of rats to electric shocks induces social avoidance for about 10 days. Here we assessed social avoidance 24 h after shock exposure in rats with chemically lesioned serotonergic and noradrenergic neurons. The effects of the NMDA receptor blocker MK-801 were also studied. When the serotonin/noradrenaline balance was shifted towards serotonergic dominance via chemical lesions, the behavioral dysfunction was markedly attenuated. The disruption of serotonergic neurotransmission (that lead to noradrenergic dominance) significantly increased the behavioral deficit. Shock responding was not secondary to lesion-induced differences in social behavior. Noteworthy, the brain noradrenaline/serotonin ratio correlated negatively with shock-induced social avoidance, suggesting that the ratio rather than absolute levels are important in this respect. In line with this assumption, double lesions had minor effects on social avoidance, suggesting that these monoaminergic systems modulate, but do not mediate the behavioral deficit. The blockade of NMDA receptors abolished the development of stress-induced social avoidance both when applied before shocks and when applied before behavioral testing. We confirmed that the long-term behavioral effects of traumatic experience result from glutamatergic activation, the effects of which are mediated by NMDA receptors. The development of the behavioral deficit is modulated by the balance between serotonergic and noradrenergic neurotransmission, possibly via effects on shock-induced glutamatergic activation.

5,7-Dihydroxytryptamine↗

PubMed2006

Elevations of endogenous kynurenic acid produce spatial working memory deficits.

Kynurenic acid (KYNA) is a tryptophan metabolite that is synthesized and released by astrocytes and acts as a competitive antagonist of the glycine site of N-methyl-D-aspartate receptors at high concentrations and as a noncompetitive antagonist of the alpha7-nicotinic acetylcholine receptor at low concentrations. The discovery of increased cortical KYNA levels in schizophrenia prompted the hypothesis that elevated KYNA concentration may underlie the working memory dysfunction observed in this population that has been attributed to altered glutamatergic and/or cholinergic transmission. The present study investigated the effect of elevated endogenous KYNA on spatial working memory function in rats. Increased KYNA levels were achieved with intraperitoneal administration of kynurenine (100 mg/kg), the precursor of KYNA synthesis. Rats were treated with either kynurenine or a vehicle solution prior to testing in a radial arm maze task at various delays. Elevations of endogenous KYNA resulted in increased errors in the radial arm maze. In separate experiments, assessment of locomotor activity in an open field and latency to retrieve food reward from one of the maze arms ruled out the possibility that deficits in the maze were attributable to altered locomotor activity or motivation to consume food. These results provide evidence that increased KYNA levels produce spatial working memory deficits and are among the first to demonstrate the influence of glia-derived molecules on cognitive function. The implications for psychopathological conditions such as schizophrenia are discussed.

Animals↗

PubMed1993

The central autonomic network: functional organization, dysfunction, and perspective.

The central autonomic network (CAN) is an integral component of an internal regulation system through which the brain controls visceromotor, neuroendocrine, pain, and behavioral responses essential for survival. It includes the insular cortex, amygdala, hypothalamus, periaqueductal gray matter, parabrachial complex, nucleus of the tractus solitarius, and ventrolateral medulla. Inputs to the CAN are multiple, including viscerosensory inputs relayed on the nucleus of the tractus solitarius and humoral inputs relayed through the circumventricular organs. The CAN controls preganglionic sympathetic and parasympathetic, neuroendocrine, respiratory, and sphincter motoneurons. The CAN is characterized by reciprocal interconnections, parallel organization, state-dependent activity, and neurochemical complexity. The insular cortex and amygdala mediate high-order autonomic control, and their involvement in seizures or stroke may produce severe cardiac arrhythmias and other autonomic manifestations. The paraventricular and other hypothalamic nuclei contain mixed neuronal populations that control specific subsets of preganglionic sympathetic and parasympathetic neurons. Hypothalamic autonomic disorders commonly produce hypothermia or hyperthermia. Hyperthermia and autonomic hyperactivity occur in patients with head trauma, hydrocephalus, neuroleptic malignant syndrome, and fatal familial insomnia. In the medulla, the nucleus of the tractus solitarius and ventrolateral medulla contain a network of respiratory, cardiovagal, and vasomotor neurons. Medullary autonomic disorders may cause orthostatic hypotension, paroxysmal hypertension, and sleep apnea. Neurologic catastrophes, such as subarachnoid hemorrhage, may produce cardiac arrhythmias, myocardial injury, hypertension, and pulmonary edema. Multiple system atrophy affects preganglionic autonomic, respiratory, and neuroendocrine outputs. The CAN may be critically involved in panic disorders, essential hypertension, obesity, and other medical conditions.

Brain↗