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PubMed2026

Bidirectional causal relationships between plasma proteins, neuroimaging metrics and risk of Alzheimer's disease.

BACKGROUND: Changes in neuroimaging metrics are among the first detectable pathophysiological alterations in Alzheimer's disease (AD). Proteins are closely linked to fluctuations in neuroimaging metrics. Therefore, the analysis of the proteomic signature associated with neuroimaging metrics holds significant promise for uncovering therapeutic targets that contribute to AD. METHODS: GWAS data concerning the Brain Imaging Data Structure (BIDs). The AD cohort comprised a total of 401,661 individuals diagnosed with AD, alongside 10,520 control participants. For a bidirectional MR analysis involving neuroimaging metrics, proteomics, and AD, the methods utilized included inverse variance weighted (IVW), MR Egger, weighted median, weighted mode, and the Wald ratio approaches. RESULTS: We identified 12 neuroimaging metrics that demonstrate significant relevance to AD (thickness of the left total hemisphere, volume of the right thalamus, and et al.). These metrics are structural magnetic resonance imaging (MRI) biomarkers that remain stable throughout the entire course of AD, from the preclinical stage through mild cognitive impairment (MCI) to dementia. Additionally, we found a substantial number of 1633 proteins that also show a noteworthy causal relationship with AD. Functional enrichment analysis indicated that these proteins were predominantly focused within various pathways linked to AD, encompassing those involved in the synaptic vesicle cycle, synaptic membranes, neurotransmitter release, and the activity of GABA receptors. In addition, our research indicates that the significant relationships observed between the identified proteins and AD are influenced by neuroimaging metrics. Notably, we found that these neuroimaging metrics play a crucial role in mediating a substantial 67% of the inverse relationship that exists between PTPRC and the phenotypic characteristics associated with AD. CONCLUSIONS: This study successfully establishes a connection between proteomic and neuroimaging metrics, as well as the AD that influence them. By creating this relationship, the research offers important information that aids in comprehending the intricate mechanisms involved in AD.

Alzheimer Disease↗

PubMed1993

Activation of the medial septal area attenuates LTP of the lateral perforant path and enhances heterosynaptic LTD of the medial perforant path in aged rats.

Age-related memory impairments may be due to dysfunction of the septohippocampal system. The medial septal area (MSA) provides the major cholinergic projection to the hippocampus and is critical for memory. Knowledge of the neurobiological mechanisms by which the cholinergic system can attenuate age-related memory loss can facilitate the development of effective cognitive enhancers. At present, one of the best neurobiological models of memory formation is long-term potentiation/long-term depression (LTP/LTD). In previous studies, intraseptal infusion of the muscarinic agonist oxotremorine, which excites MSA neurons, improved memory in aged rats. The present study examined LTP and LTD in aged Fisher 344 rats following intraseptal infusion of oxotremorine. LTP and LTD were assessed using the slope of the EPSP recorded from the hilar region of the dentate gyrus. Induction of LTP was blocked in the lateral perforant path, but not in the medial perforant path, following intraseptal infusions of oxotremorine. The generation and amplitude of heterosynaptic LTD was enhanced in the medial perforant path, but not in the lateral perforant path. The results provide evidence that pharmacological activation of the MSA can modulate LTP and LTD in the hippocampus of aged rats. The implications of these results with respect to memory and synaptic plasticity in the hippocampus are discussed.

Aging↗

PubMed2004

The physiology of learning and memory: role of peptides and stress.

The neuropeptides, as well as their respective receptors, are widely distributed throughout the mammalian central nervous system. During learning and memory processes, besides structural synaptic remodeling, changes are observed at molecular and metabolic levels with the alterations in neurotransmitter and neuropeptide synthesis and release. While there is consensus that brain cholinergic neurotransmission plays a critical role in the processes related to learning and memory, it is also well known that these functions are influenced by a tremendous number of neuropeptides and non-peptide molecules. Arginine vasopressin (AVP), oxytocin, angiotensin II, insulin, growth factors, serotonin (5-HT), melanin concentrating hormone, histamine, bombesin and gastrin-releasing peptide (GRP), glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), dopamine, corticotropin releasing factor (CRF) have modulatory effects on learning and memory. Among these peptides CCK, 5-HT and CRF play strategic roles in the modulation of memory processes under stressful conditions. CRF is accepted as the main neuropeptide involved in both physical and emotional stress, with a protective role during stress, possibly through the activation of the hypothalamo-pitiuitary (HPA) axis. The peptide CCK has been proposed to facilitate memory processing and CCK-like immunoreactivity in the hypothalamus was observed upon stress exposure, suggesting that CCK may participate in the central control of stress response and stress-induced memory dysfunction. On the other hand, 5-HT appears to play a role in behaviors that involve a high cognitive demand and stress exposure activates serotonergic systems in a variety of brain regions. The physiological role and therapeutic efficacy of various neuropeptides and the impact of stress exposure in the acquisition and consolidation of memory will be reviewed thoroughly.

Animals↗

PubMed2003

Motor training compensates for cerebellar dysfunctions caused by oligodendrocyte ablation.

The role played by oligodendrocytes (OLs), the myelinating cells of the CNS, during brain development has not been fully explored. We have addressed this question by inducing a temporal and reversible ablation of OLs on postnatal CNS development. OL ablation in newborn mice leads to a profound alteration in the structure of the cerebellar cortex, which can be progressively rescued by newly generated cells, leading to a delayed myelination. Nevertheless, the temporal shift of the OL proliferation and myelinating program cannot completely compensate for developmental defects, resulting in impaired motor functions in the adult. Strikingly, we show that, despite these abnormalities, epigenetic factors, such as motor training, are able to fully rescue cerebellar-directed motor skills.

Animals↗

PubMed2004

Group I metabotropic glutamate receptor activation produces a direct excitation of identified septohippocampal cholinergic neurons.

Septohippocampal cholinergic neurons innervate the hippocampus and provide it with almost its entire acetylcholine. Axon collaterals of these neurons also release acetylcholine within the septum and thereby maintain the firing activity of septohippocampal GABAergic neurons. A loss of septohippocampal cholinergic neurons occurs in various neurodegenerative disorders associated with cognitive dysfunctions. group I metabotropic glutamate receptors have been implicated in septohippocampal-dependent learning and memory tasks. In the present study, we examined the physiological and pharmacological effects of a potent and selective group I metabotropic glutamate receptor (mGluR) agonist S-3,5-dihydroxyphenylglycine (DHPG) on rat septohippocampal cholinergic neurons that were identified in brain slices using a selective fluorescent marker. In whole cell recordings, DHPG produced a reversible, reproducible and a direct postsynaptic and concentration-dependent excitation in 100% of septohippocampal cholinergic neurons tested with an EC(50) of 2.1 microM. Pharmacologically, the effects of DHPG were partially/completely reduced by the mGluR1 antagonists, 7-hydrox-iminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester and (+)-2-methyl-4-carboxyphenylglycine. Addition of the mGluR5 antagonist, 2-methyl-6-(phenylethnyl)pyridine hydrochloride, reduced the remaining response to DHPG, suggesting involvement of both receptor subtypes in a subpopulation of septohippocampal cholinergic neurons. In double-immunolabeling studies, 74% of septohippocampal cholinergic neurons co-localized mGluR1alpha-immunoreactivity and 35% co-localized mGluR5-immunoreactivity. Double-immunolabeling studies at the light and electron-microscopic levels showed that vesicular glutamate transporter 2 terminals make asymmetric synaptic contacts with septohippocampal cholinergic neurons. These findings may be of significance in treatment of cognitive deficits associated with neurodegenerative disorders as a group I mGluR-mediated activation of septohippocampal cholinergic neurons would enhance the release of acetylcholine both in the hippocampus and in the septum.

Animals↗

PubMed1995

[Carbon-11 labeled diacylglycerol for signal transduction imaging by positron CT: evaluation of the quality and safety for clinical use].

To elucidate the synaptic transmission in the neural system, we have been developing fundamental studies for intracellular signaling. For clinical application of carbon-11 labeled diacylglycerol (1-[1-11C]butyryl-2-palmitoyl-rac-glycerol: 11C-DAG) using positron emission computed tomography (PET), we evaluated the quality and the safety of 11C-DAG as the solution for injection. As a result, 11C-DAG was synthesized within 50 minutes, including the preparation step for injection. The half life time and energy spectrum of 11C-DAG were the same as the physical character of carbon-11, and other radioisotopes were not detected. In the quality control, 11C-DAG solution was negative in the examination of bacterial contamination and the pyrogen test in three successive synthesis procedures. In the acute toxicity test by administration of 11C-DAG and 100 mumol/kg of non-radioactive DAG to the rat intravenously, the systemic condition of the rat was not changed and no abnormalities were found in any organ 24 hours after administration. These findings indicated the safety of 11C-DAG solution. Clinical application of 11C-DAG using positron emission tomography may be useful to elucidate the dysfunction of intracellular signaling in disorders of higher cortical function such as Alzheimer disease.

Animals↗

PubMed2004

Idiopathic pure sudomotor failure: anhidrosis due to deficits in cholinergic transmission.

BACKGROUND: Acquired idiopathic generalized anhidrosis (AIGA) represents a heterogeneous clinical syndrome including sudomotor neuropathy and failure of the sweat glands. However, most AIGA cases comprise idiopathic pure sudomotor failure (IPSF), a distinct subgroup without sudomotor neuropathy or sweat gland failure. METHODS: Eight patients with IPSF (mean +/- SD age 20 +/- 5 years) were assessed by thermoregulatory and pilocarpine-induced sweating tests, as well as emotional sweating using sudorometer (4 cases), microneurography of skin sympathetic nerve activity (2 cases), and skin biopsies from the forearm or axilla (3 cases). RESULTS: Clinical features of IPSF comprise early onset; acute or sudden onset; concomitant sharp pain or cholinergic urticaria over the entire body; lack of autonomic dysfunction other than generalized anhidrosis; elevated serum IgE levels; and marked response to steroid. Sudomotor function testing revealed complete absence of thermoregulatory sweating, but well-preserved emotional sweating; pilocarpine did not induce sweating, and microneurography revealed that bursts of skin sympathetic nerve activity were not decreased; and skin biopsy displayed no morphologic abnormalities in sweat glands. The first two findings suggest lesions on the postsynaptic side of the nerve-sweat gland junction. CONCLUSION: The lesions in IPSF may be in the muscarinic cholinergic receptors of sweat glands. Allergic mechanisms are probably involved in its pathophysiology.

Adolescent↗

PubMed1992

Effect of tetrodotoxin on the phasic and tonic responses of isolated rabbit urinary bladder smooth muscle to field stimulation.

The response of the rabbit urinary bladder to field stimulation (80 volts, 2-32 Hz, 1 msec duration) is biphasic, consisting of an initial phasic contraction mediated by cholinergic and purinergic neurotransmitters, followed by a prolonged tonic contraction which is solely cholinergic. Obstructive hypertrophy of the bladder induces a variety of contractile alterations including a significantly greater reduction in the tonic component of the contractile response as compared to the phasic component. This results in a severe dysfunction in the ability of the bladder to empty. One possibility is that the inability of the bladder to maintain tension and empty efficiently may be related to a degeneration of nerves innervating the bladder smooth muscle. In addition to the well documented neuropathy, the bladder undergoes hypertrophy +/- hyperplasia of both smooth muscle and interstitial cellular elements, alterations in the metabolism of substrates, alterations in the synthesis of structural and smooth muscle proteins, and alterations in the deposition of collagen. The purpose of this study was to 1) to create a specific neuropathy in the absence of the additional structural, smooth muscle, and metabolic changes that are induced by partial outlet obstruction; and 2) determine if the contractile dysfunctions induced by the neuropathy have properties similar to the contractile dysfunctions induced by outlet obstruction. In the present study, a progressive "smooth muscle neuropathy" was induced in isolated strips of male rabbit urinary bladder smooth muscle by incubating isolated strips of urinary bladder body in the presence of increasing concentrations of tetrodotoxin (15-1500 nM). In these studies, we determined the effect of increasing concentrations of tetrodotoxin (TTX) on the response to field stimulation utilizing 2 Hz and 32 Hz, at 80 V and 1 ms duration. The effects of TTX on maximum rate of contraction, peak contraction and tonic contraction were monitored. In addition, the effects of atropine (cholinergic muscarinic blockage) and ATP-desensitization (purinergic inhibition) on the effects of TTX were also determined. The results can be summarized as follows: 1) Both atropine and ATP desensitization individually inhibited significantly the peak response to field stimulation. 2) Atropine abolished the tonic response. 3) TTX inhibited the tonic contraction at significantly lower concentrations than it inhibited peak contraction. Thus, at low concentrations of TTX, a condition similar to that seen in obstructive hypertrophy was created. 4) The ED50 in the presence of atropine was significantly greater than the ED50 following ATP desensitization. This may indicate that there are separate synaptic elements for cholinergic and purinergic transmission.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

PubMed1996

Pyramidal neurone modulation: a therapeutic target for Alzheimer's disease.

It is proposed that pyramidal neurones are central to the pathogenesis and cognitive dysfunction of AD on the basis that they are the site of tangle formation and the mismetabolism of APP and degenerate, and that such cells are the focus of neurotransmitter abnormalities. Anatomical studies in animal and human brain are revealing which neurotransmitter receptors are present on populations of pyramidal neurones and a microdialysis approach has demonstrated the ability of such receptors to alter neuronal activity. Specifically, it is proposed that cholinomimetics used for the symptomatic treatment of AD may work by influencing the activity of pyramidal neurones and that this action may be potentiated by a 5-HT1A antagonist. The contribution of pyramidal neurone transmission failure to the spread of pathology in AD is the subject of continuing investigation.

Alzheimer Disease↗

PubMed2006

Behavioral motor dysfunction in Kv3-type potassium channel-deficient mice.

The voltage-gated potassium channels Kv3.1 and Kv3.3 are expressed in several distinct neuronal subpopulations in brain areas known to be involved in motor control such as cortex, basal ganglia and cerebellum. Depending on the lack of Kv3.1 or Kv3.3 channel subunits, mutant mice show different Kv3-null allele-dependent behavioral alterations that include constitutive hyperactivity, sleep loss, impaired motor performance and, in the case of the Kv3.1/Kv3.3 double mutant, also severe ataxia, tremor and myoclonus (Espinosa et al. 2001, J Neurosci 21, 6657-6665, Genes, Brain Behav 3, 90-100). The lack of Kv3.1 channel subunits is mainly responsible for the constitutively increased locomotor activity and for sleep loss, whereas the absence of Kv3.3 subunits affects cerebellar function, in particular Purkinje cell discharges and olivocerebellar system properties (McMahon et al. 2004, Eur J Neurosci 19, 3317-3327). Here, we describe two sensitive and non-invasive tests to reliably quantify normal and abnormal motor functions, and we apply these tests to characterize motor dysfunction in Kv3-mutant mice. In contrast to wildtype and Kv3.1-single mutants, Kv3.3-single mutants and Kv3 mutants lacking three and four Kv3 alleles display Kv3-null allele-dependent gait alterations. Although the Kv3-null allele-dependent gait changes correlate with reduced motor performance, they appear to not affect the training-induced improvement of motor performance. These findings suggest that altered cerebellar physiology in the absence of Kv3.3 channels is responsible for impaired motor task execution but not motor task learning.

Animals↗

PubMed2002

Lambert-Eaton myasthenic syndrome in children.

Lambert-Eaton myasthenic syndrome is a presynaptic disorder of neuromuscular transmission. It is characterized by muscle weakness, hyporeflexia, and autonomic dysfunction. It is most often associated with small cell carcinomas of the lung. Rare cases have been reported in children. We recently encountered two children with Lambert-Eaton myasthenic syndrome associated with antibodies to P/Q-type calcium channel but without evidence of neoplasms. Both patients showed prolonged and significant improvement following cyclosporin treatment. The diagnosis of Lambert-Eaton myasthenic syndrome should be considered in children with progressive weakness and a negative work-up for the usual causes. High-frequency repetitive nerve stimulation and P/Q-type calcium-channel antibodies may confirm the diagnosis.

Autoantibodies↗

PubMed1995

Neuromuscular complications of sepsis in children.

Sepsis occurs frequently in the pediatric intensive care unit and is a significant cause of morbidity and mortality. Multiple organ systems are adversely affected by sepsis. Approximately 70% of adult patients with sepsis have peripheral nervous system dysfunction on electrophysiologic studies, of whom 30% are symptomatic. Neuromuscular dysfunction in children with sepsis is increasingly reported; however, the incidence remains undefined. Flaccid quadriplegia with the inability to wean from ventilatory support despite full cardiopulmonary recovery is the typical presentation. However, lesser degrees of weakness may be demonstrated with careful evaluation. Electrophysiologic studies often demonstrate the presence of axonal polyneuropathies, abnormalities of neuromuscular transmission, or acute myopathies. Identifiable neuromuscular syndromes in children with sepsis include critical illness polyneuropathy, pure motor polyneuropathy, thick-filament myopathy, and necrotizing myopathy. The common underlying pathogenic process in these syndromes appears to be sepsis, which may be accentuated by the administration of steroids or neuromuscular blocking agents. Recovery in strength usually occurs over a period of weeks to months.

Adult↗

PubMed1997

Expression of myosin VIIA during mouse embryogenesis.

The gene encoding myosin VIIA is responsible for the mouse shaker-1 phenotype, which consists of deafness and balance deficiency related to cochlear and vestibular neuroepithelial defects. In humans, a defective myosin VIIA gene is responsible for Usher syndrome type IB, which associates congenital deafness, vestibular dysfunction and retinitis pigmentosa. In an attempt to progress in the understanding of the function(s) of myosin VIIA, we studied the expression of the myosin VIIA gene during mouse embryonic development. Embryos from day 9 (E9) to E18 were analyzed by in situ hybridization and immunohistofluorescence. The myosin VIIA mRNA and protein were consistently detected in the same embryonic tissues throughout development. Myosin VIIA was first observed in the otic vesicle at E9, and later in a variety of tissues. The olfactory epithelium and the liver express it as early as E10. In the retinal pigment epithelium, choroid plexus, adrenal gland and tongue, expression begins at E12 and in the testis and the adenohypophysis at E13. In the small intestine, kidney and hair follicles of the vibrissae, expression of myosin VIIA starts only at E15. Myosin VIIA expression was observed only in epithelial cell types, most of which possess microvilli or cilia. Interestingly, myosin VIIA expression seems to be concomitant with the appearance of these structures in the epithelial cells, suggesting a role for this myosin in their morphogenesis. The cellular location of myosin VIIA within sensory hair cells and olfactory receptor neurons also argues for a role of this protein in the synaptic vesicle trafficking.

Adrenal Glands↗

PubMed1997

Impairment of glucose and glutamate transport and induction of mitochondrial oxidative stress and dysfunction in synaptosomes by amyloid beta-peptide: role of the lipid peroxidation product 4-hydroxynonenal.

Deposits of amyloid beta-peptide (A beta), reduced glucose uptake into brain cells, oxidative damage to cellular proteins and lipids, and excitotoxic mechanisms have all been suggested to play roles in the neurodegenerative process in Alzheimer's disease. Synapse loss is closely correlated with cognitive impairments in Alzheimer's disease, suggesting that the synapse may be the site at which degenerative mechanisms are initiated and propagated. We report that A beta causes oxyradical-mediated impairment of glucose transport, glutamate transport, and mitochondrial function in rat neocortical synaptosomes. A beta induced membrane lipid peroxidation in synaptosomes that occurred within 1 h of exposure; significant decreases in glucose transport occurred within 1 h of exposure to A beta and decreased further with time. The lipid peroxidation product 4-hydroxynonenal conjugated to synaptosomal proteins and impaired glucose transport; several antioxidants prevented A beta-induced impairment of glucose transport, indicating that lipid peroxidation was causally linked to this adverse action of A beta. FeSO4 (an initiator of lipid peroxidation), A beta, and 4-hydroxynonenal each induced accumulation of mitochondrial reactive oxygen species, caused concentration-dependent decreases in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction, and reduced cellular ATP levels significantly. A beta also impaired glutamate transport, an effect blocked by antioxidants. These data suggest that A beta induces membrane lipid peroxidation, which results in impairment of the function of membrane glucose and glutamate transporters, altered mitochondrial function, and a deficit in ATP levels; 4-hydroxynonenal appears to be a mediator of these actions of A beta. These data suggest that oxidative stress occurring at synapses may contribute to the reduced glucose uptake and synaptic degeneration that occurs in Alzheimer's disease patients. They further suggest a sequence of events whereby oxidative stress promotes excitotoxic synaptic degeneration and neuronal cell death in a variety of different neurodegenerative disorders.

Aldehydes↗

PubMed1979

Pathobiology of cortical neurons in metabolic and unclassified amentias.

Visualization of the neuron in its entirety through the use of the rapid Golgi method has permitted detection of several pathobiological features of neurons that are intimately associated with profound mental retardation in infants and children. In cases of unclassified mental retardation, dendrites and particularly dendritic spines exhibit severe developmental abnormalities. Dendritic spines, the postsynaptic components of axospinodendritic synapses, may be absent or abnormally long and thin in retardates. Evidence is presented that some cases of progressive neurobehavioral deterioration in infancy and early childhood may be due to progressive degeneration of dendritic spine systems (dendritic spine "dysgenesis"). Golgi and electron microscopic studies of neurons in human and feline ganglioside storage diseases indicate that ganglioside accumulation in cortical neurons initiates several complex alterations in neuronal geometry and morphology. Small and medium pyramidal cells form massive structural compartments (meganeurites) that frequently give rise to secondary neurites and other embryonic growth processes. Meganeurites may possess spines and spine-synapses. Other cells such as large pyramidal neurons may exhibit many somatic spines, whereas intrinsic cells of the cortex (and caudate) are unaffected morphologically by ganglioside accumulation. It is suggested that neuronal geometry distortion and aberrant synaptogenesis are important factors in the onset of neuronal dysfunction in ganglioside storage disorders. These studies also point to an important role of gangliosides in neurite formation in immature mammalian cortical neurons. Perisomatic processes and somatic spines are normal morphological components of the cell body of Purkinje cells through the 28th fetal week of human gestation. By 36 weeks the Purkinje cell somas exhibit a smooth surface contour. Prominent polydendritic processes, perisomatic protuberances, and somatic spines are detectable by Golgi methods applied to Purkinje cells in Menkes' disease and Down's syndrome long after these somatic components should normally disappear. Thus Purkinje cell soma membrane differentiation is a particularly sensitive process that can provide information on mechanisms of site-specific membrane regulation.

Brain Diseases, Metabolic↗

PubMed2006

[Intraoperative neuromonitoring of the recurrent laryngeal nerve - results and learning curve].

Intraoperative neuromonitoring was introduced in thyroid surgery several years ago resulting in a facilitated identification of the recurrent laryngeal nerve and less recurrent laryngeal nerve injuries. Between 1999 and 2004 data of all patients (n=937) undergoing thyroid resection were recorded prospectively and analyzed yearly. The intraoperative identification of recurrent laryngeal nerve succeeded in 99.2% (1665 nerves at risk). The percentage of completely resecting surgical procedures raised from 17% to 56%. Minimal vocal cord dysfunction associated with hematoma and edema in most cases was diagnosed laryngosopically in 1.4-2.4%. Transient recurrent nerve palsies were seen in 2.3% without changes throughout the years. The permanent palsy rate of 0.8% in the first years decreased. No permanent palsies were diagnosed in the last 3 years. Routine introduction of intraoperative neuromonitoring in thyroid surgery is associated with a demonstrable learning curve lasting several years. Permanent palsy rate is decreased. The rate of minimal vocal cord movement disorders and transient recurrent laryngeal nerve palsies is not changed.

Adult↗

PubMed2004

Orexin (hypocretin)/dynorphin neurons control GABAergic inputs to tuberomammillary neurons.

High activity of the histaminergic neurons in the tuberomammillary (TM) nucleus increases wakefulness, and their firing rate is highest during waking and lowest during rapid eye movement sleep. The TM neurons receive a prominent innervation from sleep-active gamma-aminobutyric acidergic (GABAergic) neurons in the ventrolateral preoptic nucleus, which inhibits them during sleep. They also receive an excitatory input from the orexin- and dynorphin-containing neurons in the lateral hypothalamus, which are critically involved in sleep regulation and whose dysfunction causes narcolepsy. We have used intracellular recordings and immunohistochemistry to study if orexin neurons exert control over the GABAergic inputs to TM neurons in rat hypothalamic slices. Dynorphin suppressed GABAergic inputs and thus disinhibits the TM neurons, acting in concert with orexin to increase the excitability of these neurons. In contrast, both orexin-A and orexin-B markedly increased the frequency of GABAergic potentials, while co-application of orexin and dynorphin produced responses similar to dynorphin alone. Thus, orexins excite TM neurons directly and by disinhibition, gated by dynorphin. These data might explain some of the neuropathology of narcolepsy.

Animals↗

PubMed1995

Autonomic neuropathy in chronic alcoholism: evaluation of cardiovascular, pupillary and sympathetic skin responses.

Autonomic nerve function was evaluated in 30 alcoholics and 30 healthy subjects by means of cardiovascular function tests, pupil cycle time (PCT), and sympathetic skin responses (SSR). Nutritional status was assessed by anthropometric parameters. Autonomic cardiovascular dysfunction was classified as early involvement in 5 patients, definite in 8, severe in 6 and atypical in 3. PCT was abnormal in 17 alcoholics. The duration of PCT became progressively longer as the severity of cardiovascular involvement increased. SSR was absent in 4 alcoholics in the palm and in 16 in the sole. These findings indicate that sympathetic and parasympathetic mediated functions are abnormal in chronic alcoholics with a similar frequency, involving different sites of the autonomic nervous system under variable patterns. Significant correlations between nutritional status and autonomic neuropathy were found.

Adult↗