ExSTED microscopy reveals contrasting functions of dopamine and somatostatin CSF-c neurons along the lamprey central canal.

Cerebrospinal fluid-contacting (CSF-c) neurons line the central canal of the spinal cord and a subtype of CSF-c neurons expressing somatostatin, forms a homeostatic pH regulating system. Despite their importance, their intricate spatial organization is poorly understood. The function of another subtype of CSF-c neurons expressing dopamine is also investigated. Imaging methods with a high spatial resolution (5-10 nm) are used to resolve the synaptic and ciliary compartments of each individual cell in the spinal cord of the lamprey to elucidate their signalling pathways and to dissect the cellular organization. Here, light-sheet and expansion microscopy resolved the persistent ventral and lateral organization of dopamine- and somatostatin-expressing CSF-c neuronal subtypes. The density of somatostatin-containing dense-core vesicles, resolved by stimulated emission depletion microscopy, was shown to be markedly reduced upon each exposure to either alkaline or acidic pH and being part of a homeostatic response inhibiting movements. Their cilia symmetry was unravelled by stimulated emission depletion microscopy in expanded tissues as sensory with 9 + 0 microtubule duplets. The dopaminergic CSF-c neurons on the other hand have a motile cilium with the characteristic 9 + 2 duplets and are insensitive to pH changes. This novel experimental workflow elucidates the functional role of CSF-c neuron subtypes in situ paving the way for further spatial and functional cell-type classification.

Discovery of Novel Biomarkers for Diagnosing and Predicting the Progression of Multiple Sclerosis Using TMT-Based Quantitative Proteomics.

Objective: Here, we aimed to identify protein biomarkers that could rapidly and accurately diagnose multiple sclerosis (MS) using a highly sensitive proteomic immunoassay. Methods: Tandem mass tag (TMT) quantitative proteomic analysis was performed to determine the differentially expressed proteins (DEPs) in cerebrospinal fluid (CSF) samples collected from 10 patients with MS and 10 non-inflammatory neurological controls (NINCs). The DEPs were analyzed using bioinformatics tools, and the candidate proteins were validated using the ELISA method in another cohort comprising 160 samples (paired CSF and plasma of 40 patients with MS, CSF of 40 NINCs, and plasma of 40 healthy individuals). Receiver operating characteristic (ROC) curves were used to determine the diagnostic potential of this method. Results: Compared to NINCs, we identified 83 CSF-specific DEPs out of a total of 343 proteins in MS patients. Gene ontology (GO) enrichment analysis revealed that these DEPs are mainly involved in platelet degranulation, negative regulation of proteolysis, and post-translational protein modification. Pathway enrichment analysis revealed that the complement and coagulation cascades, Ras signaling pathway, and PI3K-Akt signaling pathway are the main components. Insulin-like growth factor-binding protein 7 (IGFBP7), insulin-like growth factor 2 (IGF2), and somatostatin (SST) were identified as the potential proteins with high scores, degree, and centrality in the protein-protein interaction (PPI) network. We validated the expression of these three proteins using ELISA. Compared to NINCs, the level of CSF IGFBP7 was significantly upregulated, and the level of CSF SST was significantly downregulated in the MS group. Conclusion: Our results suggest that SST and IGFBP7 might be associated with the pathogenesis of MS and would be helpful in diagnosing MS. Since IGFBP7 was used to classify relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) patients, therefore, it may act as a potential key marker and therapeutic target in MS.

Somatostatin preserved blood brain barrier against cytokine induced alterations: possible role in multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory neurological disorder associated with demyelination, impaired blood brain barrier (BBB), axonal damage and neuronal loss. In the present study, we measured somatostatin (SST) and tumor necrosis factor-α (TNF-α) like immunoreactivity in CSF samples from MS and non-MS patients. We also examined the role of SST in cytokines and lipopolysaccharide (LPS)-induced damage to the BBB using human brain endothelial cells in culture. Most of the cerebrospinal fluid (CSF) samples studied from definite MS patients exhibited lower somatostatin (SST)-like immunoreactivity and higher expression of TNF-α in comparison to non-MS patients. Treatment of cells with cytokines and LPS blocked SST secretion and decreased SST expression. Human brain endothelial cells expressed all five somatostatin receptors (SSTRs) with increased expression of SSTR2 and 4 upon treatment with cytokines and LPS. Cytokines and LPS-induced disruption of the tight junction proteins Zonula occludens (ZO-1) organization was restored in presence of SST, SSTR2 or SSTR4 selective agonists. Furthermore, inflammation induced changes in extracellular signal-regulated kinases (ERK1/2 and ERK5) signaling and altered expression of endothelial and inducible nitric oxide synthase are modulated in presence of SST. These data indicate that decreased levels of SST contribute to failure of the BBB in MS.

A systematic literature review of cerebrospinal fluid biomarkers in delirium.

BACKGROUND: Cerebrospinal fluid (CSF) analysis has great potential to advance understanding of delirium pathophysiology. METHODS: A systematic literature review of CSF studies of DSM or ICD delirium was performed. RESULTS: In 8 studies of 235 patients, delirium was associated with: elevated serotonin metabolites, interleukin-8, cortisol, lactate and protein, and reduced somatostatin, ß-endorphin and neuron-specific enolase. Elevated acetylcholinesterase predicted poor outcome after delirium and higher dopamine metabolites were associated with psychotic features. CONCLUSIONS: No clear conclusions emerged, but the current literature suggests multiple areas for further investigation with more detailed studies.

Effects of estrogen on growth hormone pulsatility in peripheral blood and neuropeptide profiles in the cerebrospinal fluid of goats.

We previously reported that growth hormone (GH) pulses were negatively associated with neuropeptide Y (NPY) profiles in cerebrospinal fluid (CSF) of the third ventricle of Shiba goats. In addition, while most GH pulses were coincident with GH-releasing hormone (GHRH) pulses, there was no correlation between GH and somatostatin (SRIF) levels. The present study was performed to elucidate the relationship between GH pulses and these neuropeptide levels in CSF when estradiol (1.0 mg/head) was subcutaneously administered to ovariectomized goats. CSF and plasma samples were collected every 15 min for 18 h (from 6 h before to 12 h after injection). GH levels in peripheral blood and GHRH, SRIF and NPY levels in CSF were measured by radioimmunoassay. Pulse/trough characteristics and correlations were assessed by the ULTRA algorithm and cross-correlation analysis. Before estradiol was injected, significant coincidence was found between GHRH pulses and GH pulses, and negative coincidence was found between NPY troughs and GH pulses. Six to 12 h after estradiol injection, the amplitude and area under the curve (AUC) of the GH pulses were markedly increased. The duration and AUC of the GHRH pulses in the CSF were also increased, and stronger synchrony of GHRH with GH was observed. In contrast, the baseline of NPY was significantly decreased, and the negative correlation between the GH pulses and NPY troughs disappeared. The parameters of SRIF troughs were not clearly changed. These observations suggest that estrogen enhances the pattern of secretion of GH in the goat via enhancement of GHRH pulses and decrease of NPY levels.

[Effects of moxibustion at head-points on levels of somatostatin and arginine vasopressin from cerebrospinal fluid in patients with vascular dementia: a randomized controlled trial].

BACKGROUND: There are obvious changes in neuropeptides from plasma and cerebrospinal fluid in patients with vascular dementia (VaD), and regulating the levels of neuropeptides is a key for prevention and treatment of VaD. OBJECTIVE: To observe the clinical efficacy of moxibustion at head-points in treatment of vascular dementia (VaD), and assess its effects on memory-related neuropeptides. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 65 VaD patients from Acupuncture Hospital, Anhui University of Traditional Chinese Medicine, were randomly divided into moxibustion group (33 cases) and Western medicine group (32 cases). Patients in the moxibustion group were treated with indirect moxibustion with common monkshood cake for 20 min. Patients in the Western medicine group were orally administered piracetam tablets, 0.8 g for three times a day. One treatment course was 4 weeks, and they were treated for 4 treatment courses. MAIN OUTCOME MEASURES: The scores of Hasegawa's Dementia Scale (HDS), Mini-Mental State Examination (MMSE), and Activity of Daily Living Scale (ADL), as well as the levels of learning and memory-related neuropeptides from cerebrospinal fluid such as somatostatin (SS) and arginine vasopressin (AVP) were measured before and after treatment in the two groups. RESULTS: Total response rate was significantly higher in the moxibustion group than in the Western medicine group (P<0.01). There were significant differences in scores of HDS, MMSE and ADL between before and after treatment in the two groups(P<0.05 or P<0.01). After treatment, the scores of HDS, MMSE and ADL in the moxibustion group were more improved as compared with those in the Western medicine group (P<0.05 or P<0.01). The levels of SS and AVP after treatment were higher than those before treatment in the two groups(P<0.01). After treatment, the increased levels of SS and AVP were higher in the moxibustion group than in the Western medicine group (P<0.01). CONCLUSION: Moxibustion is effective in improving the clinical symptom scores and regulating the levels of neuropeptides associated with learning and memory in VaD patients.

Negative correlation between neuropeptide Y profile in the cerebrospinal fluid and growth hormone pulses in the peripheral circulation in goats.

BACKGROUND/AIMS: Growth hormone (GH) is secreted in pulsatile fashion, but the involvement of neuropeptides in the generation of GH pulses is not fully understood. The present study was conducted to elucidate the relationship between GH pulses and neuropeptide levels in the cerebrospinal fluid (CSF) of the third ventricle in ovariectomized goats. METHODS: CSF and plasma samples were collected every 15 min. Levels of plasma GH and profiles of GH-releasing hormone (GHRH), somatostatin (SRIH) and neuropeptide Y (NPY) in the CSF were measured by radioimmunoassay. Pulse/trough characteristics and correlations were assessed by the ULTRA algorithm, cross-correlation analysis and approximate entropy test. RESULTS: The periodicity of GH pulses was 2.20 h. Although most GH pulses were associated with GHRH peaks, there was no correlation between GH and GHRH or GH and SRIH. NPY levels in the CSF fluctuated episodically at 2.03-hour intervals. GH pulse peaks occurred 0-30 min after NPY troughs, and there was a significant negative cross-correlation and negative synchronicity between GH and NPY profiles. In addition, intracerobroventricular infusion of NPY suppressed GH secretagogue (KP102)-induced GH release. CONCLUSION: The periodic decrease in NPY may be involved in the generation of GH pulsatility in goats.

Growth hormone and insulin-like growth factor-I as an endocrine axis in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment with insidious onset. Neuropathological analysis of AD-affected brains reveals extensive atrophy and an accumulation of neurofibrillary tangles. Taken together, the neurochemical changes in the brain in patients with AD indicate multiple disturbances, and it seems likely that the changes are secondary to more fundamental changes in the brain. The IGF-I is a potent neurotrophic as well as a neuroprotective factor found in the brain, with a wide range of actions in both the central and the peripheral nervous systems. There is a physiological decline of the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis with ageing, and the possibility that the GH/IGF-I axis is involved in cognitive deficits has been recognized for several years. IGF-I is a critical promoter of brain development and neuronal survival, and plays a role in neuronal rescue during degenerative diseases. The investigations of GH-releasing stimulation tests, and especially of GHRH in AD, are equivocal and in some cases contradictory. The results of several studies addressing this point show varied results: superimposable response of GH to GHRH than response of GH to GHRH in controls; blunted GH to GHRH response in AD patients; higher GH concentrations in the morning; greater increase of GH to GHRH in AD patients than in controls. When an acetylcholinesterase inhibitor, such as rivastigmine, a drug for AD, is acutely administered, the area under the curve of the GH response to GHRH doubles, showing that rivastigmine is a powerful drug in the enhancement of GH release. Consequently, an emerging clinical target for improving the clinical manifestations of AD may be the activation of GH/IGF-I, which rejuvenates the axis, so resulting in an overall physiological benefit.

Somatostatin and Alzheimer's disease.

Alzheimer's disease (AD) is characterized by the cerebral deposition of senile plaques that are mainly composed of a set of peptides referred to as amyloid beta-peptides (Abeta). Among the numerous neuropeptides produced in intrinsic cortical and hippocampal neurons, somatostatin (SRIF) has been found to be the most consistently reduced in the brain and cerebrospinal fluid of AD patients. SRIF receptors (SSTR), which mediate the neuromodulatory signals of SRIF, are also markedly depleted in the AD brain, there being subtype-selective alterations in cortical areas. In the rat temporal cortex, we have shown that intracerebroventricular infusion of Abeta25-35 results in a decrease in SRIF-like immunoreactivity and in SRIF receptor subtype 2 (SSTR2) mRNA and protein levels, in correlation with a decrease in SSTR functionality. Insulin-like growth factor-I prevents the reduction in these parameters induced by Abeta25-35. Abeta has recently been demonstrated to be degraded primarily by a neutral endopeptidase, neprilysin, in the brain. SRIF regulates brain Abeta levels via modulation of neprilysin activity. Because SRIF expression in the brain declines upon aging in various mammals, including rodents, apes and humans, the aging-dependent reduction of SRIF has been hypothesized to trigger accumulation of Abeta in the brain by suppressing neprilysin action. Here we present an overview of recent advances on the role of SRIF in AD and its relationship with Abeta peptides.

Glial cell line-derived neurotrophic factor and somatostatin levels in cerebrospinal fluid of patients affected by chronic migraine and fibromyalgia.

The aim of the present study was to verify cerebrospinal fluid (CSF) levels of glial cell line-derived neurotrophic factor (GDNF) and somatostatin, both measured by sensitive immunoassay, in: 16 chronic migraine (CM) patients, 15 patients with an antecedent history of migraine without aura diagnosed as having probable chronic migraine (PCM) and probable analgesic-abuse headache (PAAH), 20 patients affected by primary fibromyalgia syndrome (PFMS), and 20 control subjects. Significantly lower levels of GDNF and somatostatin were found in the CSF of both CM and PCM + PAAH patients compared with controls (GDNF =P < 0.001, P < 0.002; somatostatin = P < 0.002, P < 0.0003), without significant difference between the two groups. PFMS patients, with and without analgesic abuse, also had significantly lower levels of both somatostatin and GDNF (P < 0.0002, P < 0.001), which did not differ from those of CM and PCM + PAAH patients. A significant positive correlation emerged between CSF values of GDNF and those of somatostatin in CM (r = 0.70, P < 0.02), PCM + PAAH (r = 0.78, P < 0.004), and PFMS patients (r = 0.68, P < 0.008). Based on experimental findings, it can be postulated that reduced CSF levels of GDNF and somatostatin in both CM and PCM + PAAH patients can contribute to sustained central sensitization underlying chronic head pain. The abuse of simple or combination analgesics does not seem to influence the biochemical changes investigated, which appear to be more strictly related to the chronic pain state, as demonstrated also for fibromyalgia.

Relationship between growth hormone (GH) pulses in the peripheral circulation and GH-releasing hormone and somatostatin profiles in the cerebrospinal fluid of goats.

Growth hormone (GH) is secreted in a pulsatile manner, but the underlying mechanisms of GH pulse generation remain to be resolved. In the present study, we investigated the relationship between GH pulses in the peripheral circulation and GH-releasing hormone (GHRH) and somatostatin (SRIF) profiles in the cerebrospinal fluid (CSF) of male goats. The effects of an intracerebroventricular (icv) injection of neuropeptide Y (NPY), galanin and ghrelin were also analyzed. Blood and CSF samples were collected every 15 min for 8 hr from the jugular vein and third ventricle, respectively. GH pulsatility in the goat was found to consist of distinct large pulses of 5 hr periodicity and small pulses of 1 hr periodicity. GHRH and SRIF in the CSF fluctuated in a pulsatile manner with 1 hr periodicity, and most of the descending phase of SRIF pulses were associated with the initiation of GH pulses. Icv injections of NPY, galanin and ghrelin stimulated GHRH release without affecting SRIF release. In addition, NPY suppressed, and galanin and ghrelin induced large GH pulses, although ghrelin was much more effective than galanin. These results suggest that an hourly fall in SRIF is involved in generating intrinsic circhoral rhythm of GH pulsatility. The mechanisms underlying the generation of large GH pulses of 5 hr periodicity remain unknown, while direct action of NPY and/or ghrelin on the pituitary might be involved.

Corticotropin-releasing factor in posttraumatic stress disorder (PTSD) with secondary psychotic symptoms, nonpsychotic PTSD, and healthy control subjects.

BACKGROUND: Recent studies have reported a high comorbidity between posttraumatic stress disorder (PTSD) and psychotic symptoms, and it has been hypothesized that PTSD with comorbid psychosis is a severe form of PTSD. Few studies have examined the neurobiology of PTSD with comorbid psychosis. If PTSD with secondary psychotic symptoms (PTSD-SP) is a severe form of PTSD, then it might be expected to show more extreme perturbations in the neuroendocrine patterns that characterize PTSD. METHODS: Patients with PTSD with secondary psychotic symptoms (PTSD-SP), PTSD without psychosis, and healthy comparison subjects were compared for differences in cerebrospinal fluid concentrations of corticotropin-releasing factor (CRF) and somatotropin-release-inhibiting hormone (SRIF). RESULTS: The PTSD-SP subjects had significantly higher mean levels of CRF than either the PTSD or control subjects (p <.01). The three groups showed similar SRIF levels. CONCLUSIONS: These data implicate abnormalities in the secretion of CRF with the production of secondary psychotic symptoms in PTSD. This finding supports the validity of PTSD-SP as a PTSD subtype and as a severe form of PTSD.

Correlation between spontaneous feeding behavior and neuropeptide Y profile in the third ventricular cerebrospinal fluid of goats.

Feeding behavior is regulated by neural signals in the hypothalamus, but secretory activities of these signals in vivo and their relationship with spontaneous feeding remain to be solved. In the present study, we investigated the correlation between neuropeptide Y (NPY) and somatostatin (SRIF) profiles in cerebrospinal fluid (CSF) and spontaneous feeding behavior in goats. CSF samples were collected every 15 min for 8 h from the third ventricle and feeding behavior was observed throughout the experimental period. The spontaneous feeding behavior, the mean duration of which was 58 min, occurred with an interval of 146 min. NPY in the CSF fluctuated in an episodic fashion with a 145 min interval. Each NPY episode was followed by spontaneous feeding with a time lag of 24 min. SRIF levels in CSF changed more frequently in a pulsatile manner and were related to neither NPY profiles nor feeding behavior. These results suggest that NPY, but not SRIF, is a physiological signal to drive feeding in goats.

Low CSF somatostatin associated with response to nimodipine in patents with affective illness.

BACKGROUND: In patients with depression, treatment with nimodipine has been shown to increase cerebrospinal fluid (CSF) somatostatin (SRIF) and ameliorate baseline global cerebral hypometabolism. This study was conducted to assess whether a low baseline level of CSF SRIF was associated with response to nimodipine treatment. METHODS: Twenty-one depressed patients underwent lumbar puncture for analysis of CSF somatostatin-like immunoreactivity (SRIF-LI) during a medication-free period and after at least 6 weeks of nimodipine monotherapy. Twenty-five healthy control subjects were utilized as a comparison group. Clinical improvement was assessed using the Clinical Global Impression Scale for Bipolar Illness. RESULTS: As predicted, baseline CSF SRIF-LI was significantly lower in eventual nimodipine responders (33.1 +/- 2.8 pg/mol) compared to eventual nonresponders [41.9 +/- 2.6 pg/mL; t(19) = 1.98, p =.03, one-tailed]. CONCLUSIONS: Low baseline CSF somatostatin in depression may be associated with response to nimodipine, which in turn may be related to the ability of nimodipine to increase CSF somatostatin.

Alzheimer disease - effect of continuous intracerebroventricular treatment with GM1 ganglioside and a systematic activation programme.

Five patients with the early-onset form of Alzheimer disease (AD) received GM1 ganglioside by continuous injection into the frontal horns of the lateral ventricles for a period of 12 months. The optimal GM1 dose varied between 20 and 30 mg/24 h. The patients were trained twice a week for 4-5 h with an individually designed cognitive programme, which included the use of a word processor. Neurological, neuropsychological, psychiatric and neurochemical examinations were performed a week before surgery and on days 30, 90, 180, 270 and 365 after surgery. The cerebrospinal fluid levels of the monoamine metabolites homovanillic acid and 5-hydroxyindoleacetic acid and the neuropeptide somatostatin increased. The regional cerebral blood flow showed a tendency to increase. The progression of deterioration was stopped, and motor performance and neuropsychological assessments improved. The patients became more active and felt safer in relation to other people and performing various activities. They had improved reading comprehension and a better feeling for language. They were able to write reports and short letters on a word processor. When interviewed at the end of the study, all 5 patients stated that they felt better, and their relatives reported that they had regained integrity and their joie de vivre.

A follow up study of suicide attempters: increase of CSF-somatostatin but no change in CSF-CRH.

Concentrations of somatostatin and corticotrophin releasing hormone (CRH), measured in cerebrospinal fluid (CSF) have been reported to be low in suicidal patients with major depressive disorder (MDD). Often have MDD patients in general, high CSF-CRH and low CSF-somatostatin concentrations, which both seem to normalise with clinical recovery. The present study was designed to look for CSF-CRH and CSF-somatostatin alterations along with clinical changes in patients studied repeatedly after a suicide attempt. Sixteen patients with different diagnoses, initially inpatients after a suicide attempt (baseline), participated. Lumbar punctures and ratings according to the Suicidal Assessment Scale (SUAS) and the Montgomery-Asberg Depression Rating Scale (MADRS) were performed while patients were drug-free (baseline) and after a median of 7 (5 to 9) months. At follow up MADRS- and SUAS-scores were significantly decreased (P<0.05), whereas CSF-somatostatin was significantly increased (P=0.013) and CSF-CRH had not changed significantly. Thus, the patients showed long-lasting low CSF-CRH concentrations, in spite of changed CSF-somatostatin concentrations and clinical amelioration.

Shunt related changes in somatostatin, neuropeptide Y, and corticotropin releasing factor concentrations in patients with normal pressure hydrocephalus.

OBJECTIVES: Recent data indicate that alterations in brain neuropeptides may play a pathogenic role in dementia. Neuropeptide Y (NPY), somastostatin (SOM), and corticotropin releasing factor (CRF) are neuropeptides involved in cognitive performance. Decreased SOM and NPY concentrations have been found in patients with normal pressure hydrocephalus and are probably the result of neuronal dysfunction, which could potentially be restored by shunting. The effects of shunt surgery on preoperative SOM, NPY, and CRF concentrations were studied. Any improvements in neuropeptide concentrations that could lead to clinically significant neuropsychological and functional changes were also investigated. METHODS: A prospective study was performed in 14 patients with normal pressure hydrocephalus syndrome with a duration of symptoms between 3 months and 12 years. Diagnosis was based on intracranial pressure (ICP) monitoring and CSF dynamics. Concentrations of SOM, NPY, and CRF in lumbar CSF were determined before shunting and again 6-9 months after surgery. A battery of neuropsychological tests and several rating functional scales were also given to patients before and after shunting. RESULTS: After shunting, SOM and CRF concentrations were significantly increased in all patients. Concentrations of NPY were increased in 12 of the 14 patients studied. The clinical condition of 13 of the 14 patients was significantly improved 6 months after surgery. This improvement was more pronounced in gait disturbances and sphincter dysfunction than in cognitive impairment. No significant differences in any of the neuropsychological tests were seen for the group of patients as a whole despite the increased neuropeptide concentrations. CONCLUSIONS: Shunting can restore SOM, NPY, and CRF concentrations even in patients with longstanding normal pressure hydrocephalus. However, despite the biochemical and clinical improvement in some areas such as ambulation and daily life activities, cognitive performance did not significantly improve. The role of neuropeptides in the diagnosis and treatment of patients with normal pressure hydrocephalus syndrome is discussed.

Processing of neuropeptide Y, galanin, and somatostatin in the cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are two prevalent neurodegenerative disorders for which the causes are unknown, except in rare familial cases. Several changes in neuropeptide levels as measured by radioimmunoassay (RIA) have been observed in these illnesses. Somatostatin (SOM) levels in cerebrospinal fluid (CSF) are consistently decreased in AD and FTD. Neuropeptide Y (NPY) levels are decreased in AD, but normal in FTD. Galanin (GAL) levels increase with the duration of illness in AD patients. The majority of studies of neuropeptides in CSF have not been verified by HPLC. The observed decrease in a neuropeptide level as measured by RIA may therefore reflect an altered synthesis or extracellular processing, resulting in neuropeptide fragments that may or may not be detected by RIA. Matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-MS) has been shown to be a powerful technique in the analysis of biological materials without any pre-treatment, by detecting peptides and proteins at a specific mass-to-charge (m/z) ratio. We studied the processing of the neuropeptides NPY, NPY, SOM and GAL in the cerebrospinal fluid of patients with AD (n = 3), FTD (n = 3) and controls (n = 2) using MALDI-MS. We found that considerable inter-individual variability exists in the rate of neuropeptide metabolism in CSF, as well as the number of peptide fragments formed. Certain patients showed differences in the processing of specific neuropeptides, relative to other patients and controls. This analysis of the metabolic processing of neuropeptides in CSF yielded a large amount of data for each individual studied. Further studies are required to determine the changes in neuropeptide processing that can be associated with AD and FTD. With further investigations using MALDI-MS analysis, it may be possible to identify a neuropeptide fragment or processing enzyme that can be correlated to these disease states.

Cerebrospinal fluid somatostatin levels in febrile seizures and epilepsy in children.

We analysed the level of cerebrospinal fluid (CSF) somatostatin in children with febrile seizures and epilepsy. In the febrile seizure group (n = 23), the somatostatin level was 83.9 +/- 11.2 pg/ml, which was significantly higher than that of age-matched controls. CSF samples obtained within 3 h of the last seizure had higher somatostatin levels (106.1 +/- 12.4 pg/ml;n = 14) than did the CSF obtained after 3 h (49.4 +/- 15.6 pg/ml;n = 9). The mean somatostatin level in the epilepsy group was 35.3 +/- 4.3 pg/ml (n = 34), and was distributed as follows: 27.6 +/- 3.6 pg/ml in the idiopathic generalized epilepsy group (n = 16), 44.0 +/- 9.4 pg/ml in the symptomatic generalized epilepsy group (n = 13), and 37.2 +/- 10.1 pg/ml in the partial epilepsy group (n = 5). The levels in each group were significantly higher than those in age-matched controls. Somatostatin is a hypothalamic tetradecapeptide with excitatory effects on neurons in children with febrile seizures and epilepsy. The finding that patients with convulsive disease had elevated levels of CSF somatostatin suggests that somatostatin release is somehow related to seizure activity. It remains to be determined whether this is due to increased release from over-active excitatory neurons or leakage from damaged or anoxic neurons, secondary to seizure activity.

Neurochemistry and delirium.

Acute confusional state or delirium is one of the most common organic brain syndromes especially in the elderly. It develops suddenly, within hours or days, and often during a period of hospitalization. In this paper we review the results of our studies on the neurochemistry of delirium.