TY - CHAP AU - Luiten, P AU - Nyakas, Csaba AU - Eisel, U AU - van der Zee, E ED - Donald, W Pfaff TI - Aging of the Brain T2 - Neuroscience in the 21st Century PB - Springer New York CY - New York, New York SN - 9781461419969 PY - 2013 SP - 2239 EP - 2272 PG - 34 DO - 10.1007/978-1-4614-1997-6_84 UR - https://m2.mtmt.hu/api/publication/2334998 ID - 2334998 LA - English DB - MTMT ER - TY - JOUR AU - Nyakas, Csaba AU - Granic, I AU - Halmy, L G AU - Banerjee, P AU - Luiten, P G M TI - The basal forebrain cholinergic system in aging and dementia.. Rescuing cholinergic neurons from neurotoxic amyloid-β42 with memantine TS - Rescuing cholinergic neurons from neurotoxic amyloid-β42 with memantine JF - BEHAVIOURAL BRAIN RESEARCH J2 - BEHAV BRAIN RES VL - 221 PY - 2011 IS - 2 SP - 594 EP - 603 PG - 10 SN - 0166-4328 DO - 10.1016/j.bbr.2010.05.033 UR - https://m2.mtmt.hu/api/publication/1661647 ID - 1661647 N1 - Megjegyzés-21950932 : FN Thomson Reuters Web of Knowledge Z9: 1 WC: Behavioral Sciences; Neurosciences Megjegyzés-21943155 Chemicals/CAS: acetylcholine, 51-84-3, 60-31-1, 66-23-9; acetylcholinesterase, 9000-81-1; choline acetyltransferase, 9012-78-6; glutamic acid, 11070-68-1, 138-15-8, 56-86-0, 6899-05-4; memantine, 19982-08-2, 41100-52-1; Amyloid beta-Peptides; Memantine, 19982-08-2; Peptide Fragments; Receptors, N-Methyl-D-Aspartate; amyloid beta-protein (1-42) Manufacturers: Forest, United States Megjegyzés-21943134 Chemicals/CAS: acetylcholine, 51-84-3, 60-31-1, 66-23-9; acetylcholinesterase, 9000-81-1; choline acetyltransferase, 9012-78-6; glutamic acid, 11070-68-1, 138-15-8, 56-86-0, 6899-05-4; memantine, 19982-08-2, 41100-52-1; Amyloid beta-Peptides; Memantine, 19982-08-2; Peptide Fragments; Receptors, N-Methyl-D-Aspartate; amyloid beta-protein (1-42) Manufacturers: Forest, United States AB - The dysfunction and loss of basal forebrain cholinergic neurons and their cortical projections are among the earliest pathological events in the pathogenesis of Alzheimer's disease (AD). The evidence pointing to cholinergic impairments come from studies that report a decline in the activity of choline acetyltransferase (ChAT) and acetylcholine esterase (AChE), acetylcholine (ACh) release and the levels of nicotinic and muscarinic receptors, and loss of cholinergic basal forebrain neurons in the AD brain. Alzheimer's disease pathology is characterized by an extensive loss of synapses and neuritic branchings which are the dominant scenario as compared to the loss of the neuronal cell bodies themselves. The appearance of cholinergic neuritic dystrophy, i.e. aberrant fibers and fiber swelling are more and more pronounced during brain aging and widely common in AD. When taking amyloid-β (Aβ) deposition as the ultimate causal factor of Alzheimer's disease the role of Aβ in cholinergic dysfunction should be considered. In that respect it has been stated that ACh release and synthesis are depressed, axonal transport is inhibited, and that ACh degradation is affected in the presence of Aβ peptides. β-Amyloid peptide 1-42, the principal constituent of the neuritic plaques seen in AD patients, is known to trigger excess amount of glutamate in the synaptic cleft by inhibiting the astroglial glutamate transporter and to increase the intracellular Ca2+ level. Based on the glutamatergic overexcitation theory of AD progression, the function of NMDA receptors and treatment with NMDA antagonists underlie some recent therapeutic applications. Memantine, a moderate affinity uncompetitive NMDA receptor antagonist interacts with its target only during states of pathological activation but does not interfere with the physiological receptor functions. In this study the neuroprotective effect of memantine on the forebrain cholinergic neurons against Aβ42 oligomers-induced toxicity was studied in an in vivo rat dementia model. We found that memantine rescued the neocortical cholinergic fibers originating from the basal forebrain cholinergic neurons, attenuated microglial activation around the intracerebral lesion sides, and improved attention and memory of Aβ42-injected rats exhibiting impaired learning and loss of cholinergic innervation of neocortex. © 2010 Elsevier B.V. LA - English DB - MTMT ER - TY - JOUR AU - Nyakas, Csaba AU - Felszeghy, Klára AU - Szabó, R AU - Keijser, J N AU - Luiten, P G M AU - Szombathelyi, Zsolt AU - Tihanyi, Károly TI - Neuroprotective effects of vinpocetine and its major metabolite cis-apovincaminic acid on nmda-induced neurotoxicity in a rat entorhinal cortex lesion model JF - CNS NEUROSCIENCE & THERAPEUTICS J2 - CNS NEUROSCI THER VL - 15 PY - 2009 IS - 2 SP - 89 EP - 99 PG - 11 SN - 1755-5930 DO - 10.1111/j.1755-5949.2009.00078.x UR - https://m2.mtmt.hu/api/publication/1661654 ID - 1661654 AB - Vinpocetine (ethyl-apovincaminate, Cavinton), a synthetic derivative of the Vinca minor alkaloid vincamine, has been used now for decades for prevention and treatment of cerebrovascular diseases predisposing to development of dementia. Both vinpocetine and its main metabolite cis-apovincaminic acid (cAVA) exert a neuroprotective type of action. Bilateral N- methyl-D-aspartate (NMDA)-induced neurodegeneration in the entorhinal cortex of rat was used as a dementia model to confirm the neuroprotective action of these compounds in vivo. NMDA- lesioned rats were treated 60 min before lesion and throughout 3 postoperative days with a 10 mg/kg intraperitoneal dose of vinpocetine or cAVA. Behavioral tests started after termination of drug treatment and consisted of novel object recognition, social discrimination, and spontaneous alternation in a Y-maze, and spatial learning in the Morris water maze. At the end of behavioral testing brains were perfused with fixative and the size of the excitotoxic neuronal lesion and that of microglial activation around the lesion were assayed quantitatively on brain sections immunostained for neuron-specific nuclear protein (NeuN) and integrin CD11b, respectively. Entorhinal NMDA lesions impaired recognition of novel objects and the new social partner, and suppressed spontaneous alternation and spatial learning performance in the Morris maze. Both vinpocetine and cAVA effectively attenuated the behavioral deficits, and significantly decreased lesion size and the region of microglia activation. Both lesion-induced attention deficit and learning disabilities were markedly alleviated by vinpocetine and cAVA. The morphological findings corroborated the behavioral observations and indicated reduced lesion size and microglia activation especially after vinpocetine treatment which supports an in vivo neuroprotective mode of action of vinpocitine and a less potent action of cAVA. © 2009 Blackwell Publishing Ltd. LA - English DB - MTMT ER -