Biomaterial Database

Animal models of Alzheimer's disease: experimental cholinergic denervation. 1988

G Smith

Department of Biological Psychiatry, New York State Psychiatric Institute, New York 10032.

Several animal models of AD have been developed, based upon the consistent finding of a presynaptic cholinergic deficit in AD. Significant cell loss in the NBM, the primary cortical cholinergic afferent, has been reported in AD. Lesions of the corresponding nuclei in the rodent and primate produce a persistent cholinergic deficit, but no consistent change in other neurotransmitter systems. Significant mnestic and cerebral metabolic deficits are observed acutely after lesion, which are responsive to pharmacological reversal and recover over time. Administration of AF64A produces similar mnestic and cholinergic deficits as NBM lesion, but these effects may be less responsive to pharmacological reversal. Administration of scopolamine, a muscarinic receptor antagonist, produces transient receptor blockade, mnestic deficits and deficits in cerebral metabolism, which can be reversed with a variety of pharmacological agents. The primary dissociations between these models and the deficits in AD are the lack of pharmacological response and recovery of function in AD patients and the presence of non-cholinergic neurochemical and cytoskeletal abnormalities. Future research should focus upon the systematic production and analysis of non-cholinergic neurotransmitter and cytoskeletal abnormalities to determine the contribution of these factors to the pathology seen in AD and the production of deficit in aged animals, which may more closely approximate the deficits in AD. The analysis of factors involved in recovery of function and pharmacological response in animal models may provide insight into potential treatment approaches to AD.

UI	MeSH Term	Description	Entries
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002799	Cholinergic Fibers	Nerve fibers liberating acetylcholine at the synapse after an impulse.	Cholinergic Fiber,Fiber, Cholinergic,Fibers, Cholinergic
D003704	Dementia	An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness.	Senile Paranoid Dementia,Amentia,Familial Dementia,Amentias,Dementia, Familial,Dementias,Dementias, Familial,Dementias, Senile Paranoid,Familial Dementias,Paranoid Dementia, Senile,Paranoid Dementias, Senile,Senile Paranoid Dementias
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000544	Alzheimer Disease	A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)	Acute Confusional Senile Dementia,Alzheimer's Diseases,Dementia, Alzheimer Type,Dementia, Senile,Presenile Alzheimer Dementia,Senile Dementia, Alzheimer Type,Alzheimer Dementia,Alzheimer Disease, Early Onset,Alzheimer Disease, Late Onset,Alzheimer Sclerosis,Alzheimer Syndrome,Alzheimer Type Senile Dementia,Alzheimer's Disease,Alzheimer's Disease, Focal Onset,Alzheimer-Type Dementia (ATD),Dementia, Presenile,Dementia, Primary Senile Degenerative,Early Onset Alzheimer Disease,Familial Alzheimer Disease (FAD),Focal Onset Alzheimer's Disease,Late Onset Alzheimer Disease,Primary Senile Degenerative Dementia,Senile Dementia, Acute Confusional,Alzheimer Dementias,Alzheimer Disease, Familial (FAD),Alzheimer Diseases,Alzheimer Type Dementia,Alzheimer Type Dementia (ATD),Alzheimers Diseases,Dementia, Alzheimer,Dementia, Alzheimer-Type (ATD),Familial Alzheimer Diseases (FAD),Presenile Dementia,Sclerosis, Alzheimer,Senile Dementia
D012601	Scopolamine	An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Its many uses include an anesthetic premedication, the treatment of URINARY INCONTINENCE and MOTION SICKNESS, an antispasmodic, and a mydriatic and cycloplegic.	Hyoscine,Scopolamine Hydrobromide,Boro-Scopol,Isopto Hyoscine,Kwells,Scoburen,Scopace,Scopoderm TTS,Scopolamine Cooper,Transderm Scop,Transderm-V,Travacalm HO,Vorigeno,Boro Scopol,Transderm V
D013377	Substantia Innominata	Tissue in the BASAL FOREBRAIN inferior to the anterior perforated substance, and anterior to the GLOBUS PALLIDUS and ansa lenticularis. It contains the BASAL NUCLEUS OF MEYNERT.	Innominata, Substantia