vasoactive-intestinal-peptide and Epilepsy

The neural elements of the rostral diencephalon in the mammal have been implicated in the regulation of body temperature. Moreover, it may be the neural elements within this region of the brain which activate the febrile mechanisms in response to pyrogen. Is it possible that the neuropeptides located within this area of the brain serve as neurochemical intermediaries involved in temperature regulation, fever, and (or) antipyresis? Central administration of several neuropeptides can elicit marked changes in the core temperature of an animal. Although most of these purative neuroregulators exert only a very minor influence on thermoregulation, a small number of the neuropeptides have been shown to have a profound effect on the system controlling this basic vegetative function. One of these peptides, arginine vasopressin (AVP) may play a role as an endogenous antipyretic. The neuroanatomical localization of this peptide, as well as its axonal projections, are consistent with such a role for this neurohypophyseal peptide in the mediation of antipyresis. In addition, current evidence suggests that AVP does function as a neurotransmitter. Examination of the febrile response to pyrogen in both the periparturient animal and the neonate indicates that an elevation in plasma levels of AVP is closely correlated with the diminution in the febrile response. Also, when AVP is perfused into punctate regions of the brain, a pyrogen-induced fever may be markedly suppressed AVP appears to act primarily within the septal area, 2- to 3-mm rostral to the anterior commissure. During the development of fever, the release of AVP is altered within these same loci. As body temperature decreases during the febrile state, there is a concomitant increase in the amount of AVP released into the extracellular fluid of these septal sites. Very recent findings suggest that AVP may have additional central neurochemical functions. For example, this peptide may be involved in the etiology of some forms of convulsive disorders. The precise manner in which body temperature is regulated by the central nervous system normally and during fever is not well understood.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adrenocorticotropic Hormone; Angiotensin II; Animals; Arginine Vasopressin; Body Temperature Regulation; Bombesin; Diencephalon; Epilepsy; Fever; Nerve Tissue Proteins; Thyrotropin-Releasing Hormone; Vasoactive Intestinal Peptide

The subiculum, a key output region of the hippocampus, is increasingly recognized as playing a crucial role in seizure initiation and spread. The subiculum consists of glutamatergic pyramidal cells, which show alterations in intrinsic excitability in the course of epilepsy, and multiple types of GABAergic interneurons, which exhibit varying characteristics in epilepsy. In this study, we aimed to assess the role of the vasoactive intestinal peptide interneurons (VIP-INs) of the ventral subiculum in the pathophysiology of temporal lobe epilepsy. We observed that an anatomically restricted inhibition of VIP-INs of the ventral subiculum was sufficient to reduce seizures in the intrahippocampal kainic acid model of epilepsy, changing the circadian rhythm of seizures, emphasizing the critical role of this small cell population in modulating TLE. As we expected, permanent unilateral or bilateral silencing of VIP-INs of the ventral subiculum in non-epileptic animals did not induce seizures or epileptiform activity. Interestingly, transient activation of VIP-INs of the ventral subiculum was enough to increase the frequency of seizures in the acute seizure model. Our results offer new perspectives on the crucial involvement of VIP-INs of the ventral subiculum in the pathophysiology of TLE. Given the observed predominant disinhibitory role of the VIP-INs input in subicular microcircuits, modifications of this input could be considered in the development of therapeutic strategies to improve seizure control.

Topics: Animals; Epilepsy; Epilepsy, Temporal Lobe; Hippocampus; Interneurons; Kainic Acid; Seizures; Vasoactive Intestinal Peptide

The anterior part of the piriform cortex (the APC) has been the focus of cortical-level studies of olfactory coding and associative processes and has attracted considerable attention as a result of a unique capacity to initiate generalized tonic-clonic seizures. Based on analysis of cytoarchitecture, connections, and immunocytochemical markers, a new subdivision of the APC and an associated deep nucleus are distinguished in the rat. As a result of its ventrorostral location in the APC, the new subdivision is termed the APC(VR). The deep nucleus is termed the pre-endopiriform nucleus (pEn) based on location and certain parallels to the endopiriform nucleus. The APC(VR) has unique features of interest for normal function: immunostaining suggests that it receives input from tufted cells in the olfactory bulb in addition to mitral cells, and it provides a heavy, rather selective projection from the piriform cortex to the ventrolateral orbital cortex (VLO), a prefrontal area where chemosensory, visual, and spatial information converges. The APC(VR) also has di- and tri-synaptic projections to the VLO via the pEn and the submedial thalamic nucleus. The pEn is of particular interest from a pathological standpoint because it corresponds in location to the physiologically defined "deep piriform cortex" ("area tempestas") from which convulsants initiate temporal lobe seizures, and blockade reduces ischemic damage to the hippocampus. Immunostaining revealed novel features of the pEn and APC(VR) that could alter excitability, including a near-absence of gamma-aminobutyric acid (GABA)ergic "cartridge" endings on axon initial segments, few cholecystokinin (CCK)-positive basket cells, and very low gamma-aminobutyric acid transporter-1 (GAT1)-like immunoreactivity. Normal functions of the APC(VR)-pEn may require a shaping of neuronal activity by inhibitory processes in a fashion that renders this region susceptible to pathological behavior.

Topics: Animals; Axons; Biotin; Calbindin 2; Calbindins; Carrier Proteins; Cholecystokinin; Dextrans; Epilepsy; GABA Plasma Membrane Transport Proteins; gamma-Aminobutyric Acid; Glutamate Decarboxylase; Immunohistochemistry; Isoenzymes; Male; Membrane Proteins; Membrane Transport Proteins; Neural Pathways; Neurons; Olfactory Pathways; Organic Anion Transporters; Parvalbumins; Phytohemagglutinins; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; S100 Calcium Binding Protein G; Smell; Vasoactive Intestinal Peptide

Basket cells, defined by axons that preferentially contact cell bodies, were studied in rat piriform (olfactory) cortex with antisera to gamma-aminobutyric acid (GABA)ergic markers (GABA, glutamate decarboxylase) and to peptides and calcium binding proteins that are expressed by basket cells. Detailed visualization of dendritic and axonal arbors was obtained by silver-gold enhancement of staining for vasoactive intestinal peptide (VIP), cholecystokinin (CCK), parvalbumin, and calbindin. Neuronal features were placed into five categories: soma-dendritic and axonal morphologies, laminar distributions of dendritic and axonal processes, and molecular phenotype. Although comparatively few forms were distinguished within each category, a highly varied co-expression of features from different categories produced a "combinatorial explosion" in the characteristics of individual neurons. Findings of particular functional interest include: dendritic distributions suggesting that somatic inhibition is mediated by feedforward as well as feedback pathways, axonal variations suggesting a differential shaping of the temporal aspects of somatic inhibition from different basket cells, evidence that different principal cell populations receive input from different combinations of basket cells, and a close association between axonal morphology and molecular phenotype. A finding of practical importance is that light microscopic measurements of boutons were diagnostic for the molecular phenotype and certain morphological attributes of basket cells. It is argued that the diversity in basket cell form in the piriform cortex, as in other areas of the cerebral cortex, reflects requirements for large numbers of specifically tailored inhibitory processes for optimal operation that cannot be met by a small number of rigidly defined neuronal populations.

Topics: Animals; Axons; Calbindins; Cell Size; Cholecystokinin; Dendrites; Epilepsy; gamma-Aminobutyric Acid; Glutamate Decarboxylase; Immunohistochemistry; Interneurons; Isoenzymes; Male; Neural Inhibition; Olfactory Pathways; Parvalbumins; Presynaptic Terminals; Rats; Rats, Sprague-Dawley; S100 Calcium Binding Protein G; Vasoactive Intestinal Peptide

To further explore the action of vasoactive intestinal polypeptide(VIP) in epileptogenesis, we made an immunocytochemical analysis and observed the alterations in VIP-energic neurons of the cerebral cortex, hippocampus and amygdaloid in rats. The animals were divided into three groups: the control, the epileptic group in which seizure was induced by injected Penicillin(PNC) intraperitoneally, and the nimodipline(NIM) group in which seizure was impressed by giving PNC after NIM, a dihydropyridine calcium entry blocker, was injected. The results showed that the number of neurons of epileptic group increased, compared with that of control group (P < 0.01), the neuronic number of the epileptic group was higher than that of the NIM group(P < 0.01), whereas there was no significant difference in neuronic number between the control group and the NIM group(P > 0.05). These suggest that VIP and Ca2+ participate in the process of epileptogenesis.

Topics: Animals; Calcium; Epilepsy; Female; Immunohistochemistry; Male; Neurons; Penicillins; Random Allocation; Rats; Rats, Wistar; Vasoactive Intestinal Peptide

The possible involvement of vasoactive intestinal polypeptide-related peptides in pentylenetetrazol (PTZ)-induced seizures in rats was investigated. The chemoconvulsant PTZ was administered (45 mg/kg i.p.) either acutely or chronically for three days. The detailed time course of changes in VIP-(1-28) and VIP-(22-28) was examined in several rat brain areas 5 and 20 min and 24 h after acute treatment and after three days chronic treatment. Ir-VIP levels dramatically decreased in all areas 5 min after PTZ injection, remained low after 20 min and progressively increased back to control values after 24 h and after three days of repeated treatment (except for the cortex). Chromatographic analysis of extracts prepared from PTZ-treated rats revealed a concomitant decrease in VIP-(1-28) and increase in VIP-(22-28). Thus VIP-(22-28) might be a product of the internal cleavage of the precursor VIP-(1-28) after its neuronal release; alternatively, VIP-(22-28) might be generated by post-transcriptional processing of VIP-(1-28), and thus be an 'independent' neuropeptide. The results suggest that VIP-(1-28)/VIP-(22-28)-containing neurons might be involved in PTZ-induced seizures in rat brain, and that VIP-(22-28) might play a role in these experimental seizures.

Topics: Amino Acid Sequence; Animals; Brain; Chromatography, High Pressure Liquid; Epilepsy; Injections, Intraperitoneal; Male; Molecular Sequence Data; Pentylenetetrazole; Peptide Fragments; Rats; Rats, Sprague-Dawley; Vasoactive Intestinal Peptide

The El (epileptic) mouse is a model of hereditary sensory precipitated temporal lobe epilepsy. We compared vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI), somatostatin-like immunoreactivity (SS-LI), and gamma-aminobutyric acid-like immunoreactivity (GABA-LI) in the mid-hippocampal region of El and C57BL/6 mice. Specific interneuron populations with VIP-LI and GABA-LI were elevated in the El mice, whereas SS-LI populations were unchanged. These neurochemical alterations may be contributing to the epileptic predisposition of El mice.

Topics: Animals; Epilepsy; gamma-Aminobutyric Acid; Hippocampus; Immunohistochemistry; Mice; Mice, Inbred C57BL; Peptides; Vasoactive Intestinal Peptide

The occurrence of seizure activity in human temporal lobe epilepsy or status epilepticus is often associated with a characteristic pattern of cell loss in the hippocampus. An experimental model that replicates this pattern of damage in normal animals by electrical stimulation of the afferent pathway to the hippocampus was developed to study changes in structure and function that occur as a result of repetitive seizures. Hippocampal granule cell seizure activity caused a persistent loss of recurrent inhibition and irreversibly damaged adjacent interneurons. Immunocytochemical staining revealed unexpectedly that gamma-aminobutyric acid (GABA)-containing neurons, thought to mediate inhibition in this region and predicted to be damaged by seizures, had survived. In contrast, there was a nearly complete loss of adjacent somatostatin-containing interneurons and mossy cells that may normally activate inhibitory neurons. These results suggest that the seizure-induced loss of a basket cell-activating system, rather than a loss of inhibitory basket cells themselves, may cause disinhibition and thereby play a role in the pathophysiology and pathology of the epileptic state.

Topics: Animals; Cholecystokinin; Disease Models, Animal; Electric Stimulation; Epilepsy; gamma-Aminobutyric Acid; Hippocampus; Immunologic Techniques; Interneurons; Male; Neural Inhibition; Rats; Somatostatin; Time Factors; Vasoactive Intestinal Peptide