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PubMed1999

Apolipoprotein E4, cholinergic integrity and the pharmacogenetics of Alzheimer's disease.

Recent evidence indicates that apolipoprotein E (apoE) plays a central role in the brain's response to injury. The coordinated expression of apoE and its receptors (the so-called LDL [low density lipoprotein] receptor family) appears to regulate the transport and internalization of cholesterol and phospholipids during the early phase of the re-innervation process in the adult brain. During dendritic remodelling and synaptogenesis, neurons progressively repress the synthesis of cholesterol in favour of cholesterol internalization through the apoE/LDL receptor pathway. The discovery a few years ago, that the apolipoprotein epsilon 4 allele found in 15% of the normal population is strongly linked to both sporadic and familial late-onset Alzheimer's disease (AD), raises the possibility that a dysfunction of the lipid transport system associated with compensatory sprouting and synaptic remodelling could be central to the AD process. The role of apoE in the central nervous system is particularly important in relation to the cholinergic system, which relies to a certain extent on the integrity of phospholipid homeostasis in neurons. Recent evidence obtained by 4 independent research teams indicates that apo epsilon 4 allele directly affects cholinergic activity in the brain of AD subjects. It was also shown to modulate the drug efficacy profile of several cholinomimetic and noncholinomimetic drugs used for the treatment of AD patients.

Adult↗

PubMed2001

Effects of T-588, a cognitive enhancer compound, on synaptic plasticity in the dentate gyrus of freely moving rats.

(1R)-1-benzo [b] thiophen-5-yl-2-[2-(diethylamino) ethoxy] ethan-1-ol hydrochloride (T-588) is a compound for the treatment of neurodegenerative disorders, including Alzheimer's disease and cerebrovascular diseases. T-588 reportedly alleviates learning and memory deficits in animal models of dementia. In the present study, we investigated the effects of T-588 on the induction and decay of long-term potentiation (LTP) and on the responses to paired-pulse (pp) stimulation in freely moving rats. Perforant path-evoked field potentials were recorded in the dentate gyrus by chronically implanted electrodes. LTP was induced by high-frequency stimulation 30 min after oral administration of T-588 (0.3 or 3 mg/kg). T-588 significantly augmented the increase in population spike amplitude and field excitatory postsynaptic potential slope after LTP induction. T-588 also prolonged the decay of augmented population spike amplitude, but had no significant effect on the response to pp stimulation. These results suggest that T-588 facilitates long-term synaptic plasticity, but not short-term synaptic plasticity in the dentate gyrus of freely moving rats. The effect of T-588 on long-term synaptic plasticity may contribute to the alleviation of learning and memory dysfunction seen in animal models.

Animals↗

PubMed1985

[Therapy of multiple sclerosis].

The routine therapy of multiple sclerosis (MS) in world-wide use today is comprised of four measures: Antiinflammatory and antiedematous treatment with ACTH or Synacthen, respectively, and corticosteroids: only during acute episodes. - High dosage, short duration, no long-term therapy. Immunosuppression with azathioprine (Imurek): Due to the relatively high risk only to use in malignant courses (frequent and severe bouts). Basic therapy with unsaturated fatty acids (sunflower oil, Naudicelle). Influencing circumscribed target symptoms (spasticity, micturition difficulties, constipation, etc.). In addition, physiotherapeutic, psychagogic and, if necessary, nursing and social measures are included. More than a decade's experience with ultrasound therapy of the lymphatic ring as developed by Selzer in over 300 MS-patients gives the impression of a reduction in bout frequency and severity. A statistical evaluation of therapeutic efficiency has so far been impossible for well-known disease-specific reasons, which hold true for all MS-treatment methods. Great practical importance within a foreseeable space of time may be reached by efforts to influence disturbance in nerve conduction and synaptic transmission as specifically caused by the demyelination process. The successful medicinal deceleration of sodium inactivation, inhibition of potassium activation and extension of the action potential, as well as specifically influencing the neurotransmitters responsible for the disturbed synaptic transmission could lead to a total recovery or improvement of dysfunction in a great many cases. Such a "global symptomatic therapy" might indeed not change the course of disease, but bring about great progress to the patient.

Adrenal Cortex Hormones↗

PubMed1996

Apolipoprotein E in the brain and its role in Alzheimer's disease.

Recent evidence indicates that apolipoprotein E (apoE) plays a central role in the brain response to injury. The coordinated expression of apoE and its main receptor, the apoE/apoB (LDL) receptor, appears to regulate the transport of cholesterol and phospholipids during the different phases of the reinnervation process. The recent discovery that a peculiar form of apoE, the apoE4, is strongly linked to both sporadic and familial late onset Alzheimer's disease (AD) raises the possibility that a dysfunction of the lipid transport system associated with compensatory sprouting and synaptic remodelling could be central to the AD process. The role of apoE in the central nervous system (CNS) is particularly important in relation to the function of the cholinergic system which relies to a certain extent on the integrity of phospholipid homeostasis in neurons. Recent evidence suggests that apoE4 allele has a direct impact on cholinergic function in AD.

Aged↗

PubMed2001

Traumatic brain injury-induced changes in gene expression and functional activity of mitochondrial cytochrome C oxidase.

Traumatic brain injury (TBI) is documented to have detrimental effects on CNS metabolism, including alterations in glucose utilization and the depression of mitochondrial oxidative phosphorylation. Studies on mitochondrial metabolism have also provided evidence for reduced activity of the cytochrome oxidase complex of the electron transport chain (complex IV) after TBI and an immediate (lhr) reduction in mitochondrial state 3 respiratory rate, which can persist for up to 14 days postinjury. Using differential display methods to screen for differences in gene expression, we have found that cytochrome c oxidase II (COII), a mitochondrial encoded subunit of complex IV, is upregulated following TBI. Since COII carries a binding site for cytochrome c in the respiratory chain, and since it is required for the passage of chain electrons to molecular oxygen, driving the production of ATP, we hypothesized that metabolic dysfunction resulting from TBI alters COII gene expression directly, perhaps influencing the synaptic plasticity that occurs during postinjury recovery processes. To test this hypothesis, we documented COII mRNA expression and complex IV (cytochrome c oxidase) functional activity at 7 days postinjury, focusing on the long-term postinjury period most closely associated with synaptic reorganization. Both central fluid percussion TBI and combined TBI and bilateral entorhinal cortical lesion were examined. At 7 days survival, differential display, RT-PCR, and Northern blot analysis of hippocampal RNA from both TBI and combined insult models showed a significant induction of COII mRNA. This long-term elevation in COII gene expression was supported by increases in COII immunobinding. By contrast, cytochrome oxidase histochemical activity within tissue sections from injured brains suggested a reduction of complex IV activity within the TBI cases, but not within animals subjected to the combined insult. These differences in cytochrome c oxidase activity were supported by in vitro assay of complex IV using cerebral cortical and hippocampal tissues. Our present results support the hypothesis that COII is selectively vulnerable to TBI and that COII differences may indicate the degree of metabolic dysfunction induced by different pathologies. Taken together, such data will better define the role of metabolic function in long-term recovery after TBI.

Animals↗

PubMed2000

Glial glutamate transporter GLT-1 down-regulation precedes delayed neuronal death in gerbil hippocampus following transient global cerebral ischemia.

Glial (GLT-1 and GLAST) and neuronal (EAAC1) high-affinity transporters mediate the sodium dependent glutamate reuptake in mammalian brain. Their dysfunction leads to neuronal damage by allowing glutamate to remain in the synaptic cleft for a longer duration. The purpose of the present study is to understand their contribution to the ischemic delayed neuronal death seen in gerbil hippocampus following transient global cerebral ischemia. The protein levels of these three transporters were studied by immunoblotting as a function of reperfusion time (6 h to 7 days) following a 10 min occlusion of bilateral common carotid arteries in gerbils. In the vulnerable hippocampus, there was a significant decrease in the protein levels of GLT-1 (by 36-46%, P < 0.05; between 1 and 3 days of reperfusion) and EAAC1 (by 42-68%, P < 0.05; between 1 and 7 days of reperfusion). Histopathological evaluation showed no neuronal loss up to 2 days of reperfusion but an extensive neuronal loss (by approximately 84%, P < 0.01) at 7 days of reperfusion in the hippocampal CA1 region. The time frame of GLT-1 dysfunction (1-3 days of reperfusion) precedes the initiation of delayed neuronal death (2-3 days of reperfusion). This suggests GLT-1 dysfunction as a contributing factor for the hippocampal neuronal death following transient global cerebral ischemia. Furthermore, decreased EAAC1 levels may contribute to GABAergic dysfunction and excitatory/inhibitory imbalance following transient global ischemia.

ATP-Binding Cassette Transporters↗

PubMed1998

Time domains of neuronal Ca2+ signaling and associative memory: steps through a calexcitin, ryanodine receptor, K+ channel cascade.

Synaptic changes that underlie associative learning and memory begin with temporally related activity of two or more independent synaptic inputs to common postsynaptic targets. In turn, temporally related molecular events regulate cytosolic Ca2+ during progressively longer-lasting time domains. Associative learning behaviors of living animals have been correlated with changes of neuronal voltage-dependent K+ currents, protein kinase C-mediated phosphorylation and synthesis of the Ca2+ and GTP-binding protein, calexcitin (CE),and increased expression of the Ca2+-releasing ryanodine receptor (type II). These molecular events, some of which have been found to be dysfunctional in Alzheimer's disease, provide means of altering dendritic excitability and thus synaptic efficacy during induction, consolidation and storage of associative memory. Apparently, such stages of behavioral learning correspond to sequential differences of Ca2+ signaling that could occur in spatially segregated dendritic compartments distributed across brain structures, such as the hippocampus.

Animals↗

PubMedDate not supplied

Alterations in synaptic transmission and plasticity in hippocampus by a complex PCB mixture, Aroclor 1254.

Developmental exposure to polychlorinated biphenyls (PCBs) has been associated with a variety of neurological effects including cognitive dysfunction. The present study assessed the effects of acute in vitro exposure to a complex mixture of highly chlorinated PCBs, Aroclor 1254 (A1254), on synaptic transmission in the hippocampus of the rat. Increases in population spike (PS) amplitude were observed in field potentials recorded from the pyramidal cell layer of CA1 in response to 1.0-3 microg/ml of A1254. PS amplitude was increased by approximately 20% 5-10 min following the beginning of exposure to 3 microg/ml A1254, with some recovery towards baseline amplitudes occurring by 30 min, despite continuous perfusion. Longer exposures revealed that a maintained 10% increase in PS amplitude persisted beyond 90 min of exposure to 3 microg/ml A1254. A second recording electrode in the stratum radiatum revealed modest increases in EPSP slope (approximately 10%) that were transient. EPSP slope changes appeared within 5 min of exposure to A1254 (3 microg/ml), peaked at 10 min, and declined to baseline levels by 30 min, despite continued perfusion with A1254. Monitoring over a protracted period revealed relatively stable EPSP slope amplitudes following the return to baseline levels. Long-term potentiation (LTP) is a model of synaptic plasticity believed to encompass the physiological substrates of memory. Neither magnitude or persistence of PS potentiation recorded from the stratum pyramidale was affected by 3 microg/ml A1254. LTP of the EPSP slope recorded in the stratum radiatum was also induced to a comparable degree in control and A1254-treated slices. However, the augmentation in the dendritic response was not maintained in the treated slices over the 60-min posttrain recording period. Acute effects of PCBs on calcium homeostasis, protein kinase C translocation, dopaminergic function, and hormonal action may contribute to the pattern of effects seen in synaptic transmission and plasticity in the hippocampus.

Animals↗

PubMed1999

4-Aminopyridine enhances motor evoked potentials following graded spinal cord compression injury in rats.

Although several experimental and clinical studies have demonstrated the ability of 4-aminopyridine (4-AP) to restore electrophysiological and/or behavioral function following chronic spinal cord injury, the mechanism by which this occurs remains unclear. Demonstration of efficacy in rat spinal cord injury has not been reported, evidently because even relatively mild spinal cord contusions that produce only minor permanent locomotor disturbances abolish hind limb myoelectric motor evoked potentials (mMEPs). In this study, mMEPs were recorded acutely 25 days following graded thoracic spinal cord compression in rats. mMEP amplitudes were significantly enhanced by a single, 2 mg/kg i.v. dose of 4-AP. mMEPs were increased in all rats showing some evoked responses initially, and also in some animals which had no responses prior to treatment. 4-AP was further found to increase the maximum following frequency of mMEPs in both normal and injured rats from about 0.1 Hz to between 1 and 10 Hz. These data suggest that 4-AP might act by enhancing synaptic efficacy, as well as enhancing conduction in spinal axons whose myelination has been rendered dysfunctional by trauma.

4-Aminopyridine↗

PubMed2001

Perturbed endoplasmic reticulum function, synaptic apoptosis and the pathogenesis of Alzheimer's disease.

Endoplasmic reticulum (ER) appears to be a focal point for alterations that result in neuronal dysfunction and death in Alzheimer's disease (AD). Aberrant proteolytic processing and/or trafficking of the beta-amyloid precursor protein (APP) in ER may promote neuronal degeneration by increasing the levels of the neurotoxic forms of beta-amyloid (A beta) and by decreasing the levels of the neuroprotective secreted form of APP (sAPP alpha). Some cases of AD are caused by mutations in the genes encoding presenilin 1 (PS1). When expressed in cultured neuronal cells and transgenic mice, PS1 mutations cause abnormalities in ER calcium homoeostasis, enhancing the calcium responses to stimuli that activate IP3- and ryanodine-sensitive ER calcium pools. Two major consequences of this disrupted ER calcium regulation are altered proteolytic processing of APP and increased vulnerability of neurons to apoptosis and excitotoxicity. The impact of PS1 mutations and aberrant APP processing is particularly great in synaptic terminals. Perturbed synaptic calcium homoeostasis promotes activation of apoptotic cascades involving production of Par-4 (prostate apoptosis response-4), mitochondrial dysfunction and caspase activation. A beta 42 (the 42-amino-acid form of A beta) induces membrane lipid peroxidation in synapses and dendrites resulting in impairment of membrane ion-motive ATPases and glucose and glutamate transporters. This disrupts synaptic ion and energy homoeostasis thereby promoting synaptic degeneration. In contrast, sAPP alpha activates signalling pathways that protect synapses against excitotoxicity and apoptosis. In the more common sporadic forms of AD, the initiating causes of the neurodegenerative cascade are less well defined, but probably involve increased levels of oxidative stress and impaired energy metabolism. Such alterations have been shown to disrupt neuronal calcium homoeostasis in experimental models, and may therefore feed into the same neurodegenerative cascade initiated by mutations in presenilins and APP. Perturbed synaptic ER calcium homoeostasis and consequent alterations in APP processing appear to be pivotal events in both sporadic and familial forms of AD.

Alzheimer Disease↗

PubMed2005

Essential role of D1 but not D2 receptors in methamphetamine-induced impairment of long-term potentiation in hippocampal-prefrontal cortex pathway.

Methamphetamine (MA) abuse induces deficits in cognitive performance that are related to dysfunction of the prefrontal cortex (PFC). The medial portion of the prefrontal cortex (mPFC) in rats that is crucial for cognitive function has been shown to undergo long-term potentiation (LTP) in the projections from the hippocampus. However, no study has been performed to evaluate the influence of MA on synaptic plasticity in the hippocampal-mPFC pathways. In the present experiments, we investigated the effects of repeated MA administration on hippocampal-mPFC LTP, together with MA-induced stereotyped behaviors. Repeated MA administration produced behavioral sensitization and LTP impairment in the hippocampal-mPFC pathways. The MA-induced impairment of hippocampal-mPFC LTP was prevented by the pretreatment of dopamine 1 (D1) but not dopamine 2 (D2) receptor antagonists, while D1 and D2 receptor antagonists attenuated the MA-induced stereotyped behaviors. These findings suggest that D1 receptors are crucial for the MA-induced deterioration of synaptic plasticity in the hippocampal-mPFC circuits. Impairment of LTP associated with D1 receptor dysfunction may underlie cognitive deficits in MA-dependent subjects.

Analysis of Variance↗

PubMed2000

Neurotrophic factors protect cortical synaptic terminals against amyloid and oxidative stress-induced impairment of glucose transport, glutamate transport and mitochondrial function.

Previous studies have shown that several different neurotrophic factors can prevent death of cortical and hippocampal neurons induced by excitotoxic and oxidative insults in cell culture and in vivo. Because neuronal degeneration may be initiated by alterations occurring in synaptic compartments in disorders ranging from Alzheimer's disease to stroke, we tested the hypothesis that neurotrophic factors can exert direct protective actions at the level of the synapse. We now report that a nine amino acid bioactive fragment of activity-dependent neurotrophic factor (ADNF-9) enhances basal glucose and glutamate transport, and attenuates oxidative impairment of glucose and glutamate transport induced by amyloid beta-peptide and Fe(2+), in neocortical synaptosomes. Preservation of transporter function required only short-term (1-2 h) pretreatments. Basic fibroblast growth factor (bFGF) was also effective in suppressing oxidative impairment of synaptic transporter functions, while nerve growth factor (NGF) was less effective. Additional analyses showed that ADNF-9, bFGF and NGF suppress oxidative stress and mitochondrial dysfunction induced by amyloid beta-peptide and Fe(2+) in synaptosomes. Our data suggest that ADNF-9 can act locally in synaptic compartments to suppress oxidative stress and preserve function of glucose and glutamate transporters. Such synapto-protective actions suggest roles for activity-dependent trophic signaling in preventing degeneration of neuronal circuits, and indicate possible therapeutic applications of agents that stimulate local synaptic (transcription-independent) neurotrophic factor signaling pathways.

Amyloid↗

PubMedDate not supplied

Hippocampal neurobiological mechanisms of age-related memory dysfunction.

Studies are reviewed which indicate that hippocampal frequency potentiation (the growth of neural responses during repetitive synaptic stimulation) is impaired in aged rats, and that this impairment may be important in learning and memory deficits found in these aged animals. Intracellular recording and ultrastructural studies suggest that both hippocampal frequency potentiation and the age deficit in such potentiation are synaptic processes (probably presynaptic), and that the deficit may be due to an age-related increase in calcium influx during depolarization. The latter could in some way result from alterations in the function of a Ca-mediated inactivation of Ca current mechanism recently found in hippocampal neurons. Since major hippocampal changes occur with aging in both rodents and humans, it seems possible that these data are also relevant to human brain aging. Consequently, it is suggested that Alzheimer's disease results from an acceleration of normal age-related neuronal calcium conductance changes by some unknown process (e.g., viruses, aluminum, genetic factors, etc.), leading to a rapid deterioration of brain structure.

Aging↗

PubMed2003

Effect of ischaemia & aglycaemia on the synaptic transmission in neonatal rat spinal cord in vitro.

BACKGROUND & OBJECTIVES: In vitro models of anoxia have revealed severe changes in neuronal functions after ischaemia but not after aglycaemia, although hypoglycaemia produced severe neuronal dysfunctions sometimes leading to coma. The present study was therefore undertaken to examine and compare the effects of aglycaemia with that of ischaemia on synaptic transmission in vitro. METHODS: Spinal cord from the neonatal rat was isolated, hemisected and placed in a chamber perfused with standard physiological solution. The stimulation of a dorsal root elicited monosynaptic (MSR) and polysynaptic (PSR) reflex potentials in the segmental ventral root. The effects of suprefusing glucose free medium (aglycaemia) and superfusing glucose free and O2 free medium (ischaemia) were examined on these reflexes. RESULTS: Superfusion of aglycaemic solution did not alter the magnitude of MSR or PSR in the first 15 min and subsequently there was a time-dependent depression of the reflexes (P < 0.05). The ischaemic solution depressed the reflexes in a time-dependent manner from the very beginning. The 50 per cent depression of the reflexes occurred around 25 and 15 min, for aglycaemia and ischaemia, respectively. In the presence of Mg2+, the aglycaemia-induced depression of MSR was completely blocked but the ischaemic response was attenuated partially as the reflex was abolished by 80 min. INTERPRETATION & CONCLUSION: The results of the present study indicate that the aglycaemia and ischaemia depressed the synaptic transmission to the same extent though there were differences in their onset and progress. Aglycaemia involves N-methyl-D-aspartate (NMDA) receptor-dependent (Mg2+ sensitive) mechanism, while ischaemia-induced depression involves other mechanisms in addition to NMDA.

Animals↗

PubMed1995

Central nervous system trans-synaptic effects of acute axonal injury: a 1H magnetic resonance spectroscopy study.

N-acetylaspartate (NAA) has previously been proposed as a neuronal marker. 1H magnetic resonance spectroscopy (MRS) is able to detect NAA in brain, and decreases of NAA have been documented after brain injury. The reason for this decrease is not fully understood and neuron loss damage and "dysfunction" have all been proposed. It is hypothesized that acute central nervous system (CNS) deafferentation causes a trans-synaptic NAA decrease and that high resolution 1H MRS is able to detect such a decrease. To test this hypothesis, an experimental model was used in which axonal lesions were obtained by stretch injury in guinea pig right optic nerve (95-99% crossed fibers). The trans-synaptic concentration of NAA, total creatine (Cr), and the NAA/Cr ratio in lateral geniculate bodies (LGB) and superior colliculi (SC) sample extracts were measured 72 h later by high resolution 1H MRS. In the left LGB/SC, which is where right optic nerve fibers project, reductions of NAA and NAA/Cr were found whereas Cr levels were normal. NAA, NAA/Cr, and Cr values were all normal in the right LGB/SC. Histology and EM findings revealed no abnormalities. At 7 days, left LGB/SC NAA and NAA/Cr values were in the normal range. It was concluded that 1) acute deafferentation in the CNS causes a trans-synaptic decrease of NAA levels that can be detected by 1H MRS and 2) NAA decrease may be due to changes of NAA metabolism caused by functional neuronal inactivity rather than neuronal loss, injury or "dysfunction." 1H MRS is a potential tool for the study of functional effect of CNS lesions in vivo.

Animals↗

PubMed2003

Expression of metabotropic glutamate receptors in rat meningeal and brain microvasculature and choroid plexus.

This study investigated the distribution of metabotropic glutamate receptors (mGluRs) in meningeal and parenchymal microvasculature and in choroid plexus by means of Western blot analysis and immunohistochemistry. Western blot analysis demonstrated mGluR expression in both rat and human leptomeningeal tissues. In the rat, mGluR expression was developmentally regulated, with only mGluR2/3 showing expression at the embryonic day 19 developmental stage. In contrast, mGluR1 alpha, mGluR2/3, mGluR4a, and mGluR7 were expressed in leptomeninges from adult rats. Immunohistochemical analyses showed intense mGluR1 alpha immunoreactivity in the pia mater and blood vessels in the subarachnoid space and in the arachnoid layer of the meninges. mGluR2/3, mGluR4a, mGluR5, and mGluR7 were also expressed in meningeal microvasculature. In addition, the parenchymal microvasculature and choroid plexus were strongly immunoreactive for mGluR1 alpha, mGluR2/3, mGluR4a, mGluR5, and mGluR7. We used antibodies specific for phenotypic markers of microvascular and glial cells to characterize the cell type(s) immunopositive for mGluRs. Comparison of staining with anti-von Willebrand factor antibody and anti-mGluR antibodies revealed that mGluR immunoreactivity was present in cells that surrounded the luminal surface labeled by the endothelial cell marker. In these cells, smooth muscle actin and mGluR immunoreactivity overlapped, suggesting that, in addition to endothelial cells, pericytes within the microvasculature also express mGluRs. Furthermore, expression of mGluR1 alpha was also observed in pure pericyte cultures isolated from bovine retina. These data suggest that glutamate by means of activation of mGluRs may have a broad sphere of physiological influence in the brain which in addition to modulating synaptic transmission may also have a role in determining microvascular function and dysfunction.

Animals↗

PubMed1997

No changes in cerebrospinal fluid levels of nitrite, nitrate and cyclic GMP with aging. Short communication.

Nitric oxide (NO) is a free radical gas that plays a role in various signal transduction processes. NO has been proposed to have a function in the mechanism of synaptic plasticity, including long-term potentiation and memory formation in vivo. Because a failure in synaptic plasticity is considered to be involved in aging-associated brain dysfunction, NO production in the brain may be altered by aging. In the present study, we measured the levels of NO metabolites, nitrite and nitrate, and cyclic GMP in the cerebrospinal fluid (CSF) of human subjects without neurological or psychiatric disorders. There were no age-related changes in the CSF levels of either nitrite, nitrate or cyclic GMP. These results suggest that NO production in the brain may be maintained during the aging process.

Adult↗

PubMed1989

VIP and autonomic neurotransmission.

A variety of peptides have been proposed as transmitter candidates in non-cholinergic, non-adrenergic nerves. The nerves containing vasoactive intestinal polypeptide (VIP), which innervate blood vessels, non-vascular smooth muscle, mucosal epithelium and glands comprise a major and wide-spread population of the peptide-containing systems. There is now experimental data supporting the view that VIP is a transmitter in non-adrenergic, non-cholinergic nerves in the digestive tract, respiratory tract and urogenital tract, controlling smooth muscle tone and motility, blood flow and secretion. It is possible that impairment of VIP-containing nerves is involved in a number of autonomic dysfunctions.

Animals↗