Abstract Extensive evidence indicates that disruption of cholinergic funtion is characteristic of aging and Alzheimer's disease (AD), and experimental manipulation of the cholinergic system in laboratory animals suggests age‐related cholinergic dysfunction may play an important role in cognitive deterioration associated with aging and AD. Recent research, however, suggests that cholinergic dysfunction does not provide a complete account of age‐related congnitive deficits and that age‐related changes in cholinergic function typically occur within the context of changes in several other neurmoudulatory systems. Evidence reviewed in this paper suggests that interactions between the cholinergic system and serveral of these neurotransmitters and neuromodulators—including norepinephrine, dopamine, serotonin, GABA, opioid peptides, galanin, substance P, and angiotensin II—may be important in learning and memory. Thus, it is important to consider not only the independent contributions of age‐related changes in neuromodulatory systems to cognitive decline, but also the contribution of interactions between these systems to the learning and memory deficits associated with again and AD.
In this review the various chemical structures of allosteric agonists and modulators of the muscarinic acetylcholine receptor subtype 1 (mAChR1 or M1) and their relevance for possible treatment of Alzheimer's disease (AD) are discussed. Furthermore, their design principles, common structural properties and their unique features with regard to structure–activity relationships (SARs), such as 'molecular switches' and 'steep/flat' SARs, are highlighted. M1 bitopic ligands and hybrid molecules are also considered. All these differently designed M1 allosteric modulators open exciting new paths in medicinal chemistry with most promising therapeutic opportunities to fight AD.
Radiofrequency (RF) or quisqualate (QUIS) lesions of the septal area were made in rats, and acquisition of the radial-arm maze and the Morris water maze was assessed. Both RF and QUIS rats learned to find the hidden platform as quickly as sham-lesioned rats in the Morris water maze, whereas RF rats were markedly impaired and QUIS rats were mildly impaired on the radial-arm maze. A spatial-discrimination version of the Morris water maze, however, revealed a deficit in RF but not QUIS rats. Interestingly, the performance of RF rats on this task was not altered by a dose of scopolamine, a muscarinic antagonist, that disrupted the performance of sham-lesioned animals. Since the relative sensitivity of these spatial tasks to disruption by septal lesions was not clearly related to spatial-mapping requirements, impaired cognitive mapping does not completely account for septal-lesion effects on memory tasks.
Im Begriff »Technology Governance« spiegelt sich ein geändertes Verständnis der Steuerbarkeit technischen Wandels und der Beschaffenheit von Regelungsstrukturen, in denen öffentliche und private Akteure zusammenwirken. Technikfolgenabschätzung (TA) behauptet sich im Governance-Prozess als wissenschaftliches Reflexionselement und strategische Wissensressource. Im Kern versucht TA, Chancen und Risken neuer Technologien auszuloten sowie auf Entwicklung und Anwendung zum größtmöglichen gesellschaftlichen Nutzen einzuwirken. Die wachsende Bedeutung technischer Innovationen im globalen Wettbewerb verstärkt den Bedarf an Folgenwissen und damit an TA. Umso dringlicher ist es, sich ihrer geeigneten Ausrichtung und Ausstattung für effektive Beiträge zur Governance technologischer Entwicklungen und für erfolgreiche Problemlösungen zu vergewissern. Dieser Band bietet Ansätze zu einer Reflexion von Voraussetzungen und Reichweite der TA aus einer Governance-Perspektive, u.a. mit Blick auf verschiedene TA-Konzepte, mögliche Funktionen und Fragen des Timings von TA im Governance-Prozess sowie eine Analyse von Mikrostrukturen der Innovationsgestaltung. Die Beiträge nehmen exemplarisch Bezug auf zahlreiche kontrovers diskutierte Technisierungsprozesse der Gegenwart.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)