THIRD INTERNATIONAL CONFERENCE ON ALZHEIMER’S DISEASE

Histochemical staining of the frozen sections from rats administered the WGA-HRP solution revealed COnCentratiO" Of the label in the olfactory nerve fiber and glomerular layers Of the olfactory bulb while rats given saline alone showed no detectable label. Spectrophotometric assays demonstrated that the concentration of enzymatically active WGA-HRP in the treated rats was 11 + 1.4 "g/g wet weight of tissue (about 180 nM) compared to only 0.5 + 0.2 uglg for rats give" 0"lY saline. This is the first quantitative assessment Of transneuronal transport of a substance into the brain following intranasal administration. The ability to achieve nanomolar concentrations of WGA-HRP in the brain is encouraging since potential therapeutic agents such as nerve growth factor, as well as diagnostic agents such as superparamagnetic MRI contrast agents, are active in the nanomolar range.

525 NEUROTROPHIC EFFECTS OF THE NOOTROPIC DRUG CEREBROLYSINR - A SUMMARY

M. WINDISCH, E. ALBRECHT, U. EGGENREICH, B. PAIER Inst.Zool.; Dept.Metabolic Physiol.; Universitat Graz, Austria

Cerebrolysin, a drug produced by biotechnological methods, using a standardized enzymatic breakdown of pig brain proteins, is successfully used in the therapy of neurodegenerative, ischemic and traumatic cerebral disorders. It consists of free amino acids and biologically active small peptides (MW < 10 kD). Experimental series proved that the drug action is mainly depending on these peptides, having metabolic and neuromodulatory activities. Histological studies of the drug effects on brain developement (1) were delivering the first results demonstrating an influence on neuronal differentiation. Similar results could be reproduced by other authors (2,3) proving the effects of Cerebrolysin on brain development and neuronal plasticity in vivo and in vitro. In the year 1988 first reports were dealing with a Nerve-Growth- factor like activity of Cerebrolysin. It was very recently possible to show a significant, dose dependent neurotrophic action of this drug on cultured neurons from different regions of the brain of chicken embryos. In vivo it was possible to show that treatment with Cerebrolysin is able to rescue the cholinergic neurons in the medial septum of the rat after fimbria fornix transsection (4). The experimental data could explain the useful actions of Cerebrolysin in the treatment of patients suffering from neurodegenerative disorders. In contrary to high-molecular growth factors having a limited applicability it could be emphasized that the small peptides of Cerebrolysin penetrate blood-brain-barrier, exerting a protective effect on sick neurons.

Cerebrolysin is produced by EBEWE Arzneimittel GesmbH, Austria

526 EFFECTOFPHOSPHATIDYLSERINEON GLUCORTICOIDSECRETIONINAGED RATS, A. Zanotti. M.G. Nunzi and D. Cocchi’. Fidia Research Labs, Abano Terme and ‘Dept. Phanacology 8 Biology, University of Bari. Italy. It has been suggesfed that high steroid levels may alter brain cell metabo. lism, the result of which may perhaps contribute to the occurrence of age- related neuro-degenerative processes. Hypothalamic- pituitary- adrenal (HPA) activity tends lo increase with age in rodents, as a function of dampened glucocorticoid negative feedback. A diminished sensitivity of Ihe feedback regulation of the HPA system lo glucocorlicoids has also been found in aged humans, particularly in demented subjects. The increased exposure lo Ihe highly catabolic adrenal hormones appears to be associated with the loss Of hippacampal neurons and the emergence of cognitive deficits in the aged rats and. most likely, in humans. Phosphatidylserine (PS), a membrane phospholipid currently used for the treatment of cognitive disturbances of the elderly, has been shown lo positively affect learning capabilities and morphological parameters in aged animals. In this work we investigated the effect of a chronic treatmenl with PS on the activity of the HPA axis in aged rats. Male and female inbred rats (Wistar- KYoto, Charles River, Calco). 19 and 20 months of age respectively (at the beginning of the trealment) ware used. PS was administered 81 the dose of 50 mg/kgldaily in the drinking water for 8 weeks. Ar the end of treatment rats

underwent a dexamethasone (DEX, 5 and lOpg/kg) suppression lest and, one week later. were exposed lo an ether Stress (2 min.) for evaluation of corticostsrone (B) secrelion. Chronic PS administration significantly reduced baseline B levels in aged rats of both sexes. without altering the Inhibitory effect of exogenously administered DEX on HPA activity. Exposure lo ether slgniflcantly increased B secretion in ~1s of both sexes independenlly from PS treatment. In rats receiving PS. however, Ihe ether- induced mcrease of 6 plasma levels was significantly lower. The above results indicate that a chronic treatment with PS 1s able lo reduce the activity of the HPA axis in aged rats. This effecr of PS might likely play a beneficial role m preventing or reducing the potential neurotoxicity 01 high circulating adrenal cortlcosterold levels associated with age-related impalrmsnt of HPA negative feed back.

527 FXOZkfJS CM-1 G?MZImIDE MAY INC!RFi!SE AUDmRY P300 LATENCY IN MZHE3MWS DISEASE T.A. Ala, J.W. lUllc& and W.H. Frey, II, Cept of Neurolcgy, Ramsey Clinic/St. Paul-RwseyMedical CenterandLhhersity ofMimes&a, St. Paul, MN 55101 U.S.A. OBTEcI?vEs: E&ermi~iftrea~ofAlzheimer's

disease (AD) patientswith theneurotrcphic factora-1 garqliceide results ina cimqe inthepatients' P300 event-related @entials. Lktemme if any dmqe may haveaclinical correlate.

BACKGKUND: Wehavereport&thattreatixntwithcM-1 for 12 weeks does not appear to have a synptcmtic effect in AD (Ala TA, et al. m Neural. 1990; 47:1126-1130). In that pilot stulywealso rem- P300 potentials as an independent, objective measure of pcssible treatment effect.

DESIGN/MEIliOffi: AD patients received 100 nq m-1 II4 daily or plac&a for 12 we&s in the double-blind sm. P300 reaxdirqs and cognitive assesgRents were done at baseline, week 12, and week 24. RESUEE: me P300 latency of the G4-1-trwlted qmup

mcrwmxl significantly frm baseline to week 12 (+20.6 _+ 31.4 met, n = 14; p = 0.029): the latemy of the placebo group did not significantly change (-1.4 _+ 34.1 msec, n = 20; p > 0.1). Themeanlatmcies of the tm groups were not statistically different at baseline, w?ek 12, or week 24. No correlation of the latency charqe with the cognitive assessnentswasnohd. amCuJs1CNs: Treabnentof AD patients with GM-lmy

resultinaninmease inthepatimts' P300 latency. Furtherstudiesare remmmwdedtodetenninethe clinicalrelemnce of this finding. Am: 'Ihis study was supported by Fidia

FharmaceUtiCal Corpomtion, Washk$on, D.C., U.S.A.

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