Biomaterial Database

Restoration of cholinergic circuitry in the hippocampus by foetal grafts. 1989

D J Clarke, and A Björklund

Department of Pharmacology, Oxford, England.

The pathway from medial septum to hippocampus is one of the major and most well-documented cholinergic connections in the rodent brain. Interruption of this pathway by either direct destruction of the cells of origin in the medial septum or by transection of the fimbria-fornix, the fibre tract along which the septohippocampal axons traverse, results in a virtually complete depletion of cholinergic markers within the hippocampal formation. Previous experiments have shown that grafts of foetal rat septal-diagonal band region placed into the denervated hippocampus can restore acetylcholinesterase (AChE) fibre density to 85-90% of control values (Björklund et al., Acta physiol. scand. Suppl. 522 (1983) 49-58). More recently, it has been demonstrated using the more specific technique of choline acetyltransferase (ChAT) immunocytochemistry in combination with electron microscopy that septal grafts are also able to restore the cholinergic connectivity at the synaptic level in the dorsal hippocampal formation. However, we have demonstrated that this restoration of both AChE and ChAT fibre density represents a specific mechanism and that the source of the foetal cholinergic neurons is crucial to the extent of reinnervation and pattern of connectivity achieved. In aged rats, judged as being behaviourally impaired with respect to their spatial memory, there appears to be an intrinsic denervation of the septohippocampal pathway such that the hippocampus is depleted of cholinergic markers. In these cases, transplantation can again restore cholinergic innervation but without the requirement of prior denervation by a fimbria-fornix transection--grafts are placed into the intact hippocampus. Results show that the grafts survive well in the aged, intact hippocampus and are able to ameliorate the behavioural impairments, perhaps by the formation of substantial numbers of cholinergic synapses between the graft and host brain. In conclusion, therefore, neural grafting of cholinergic neurons of appropriate type and origin is able to reinnervate the hippocampal formation previously denervated either by mechanical transection of the fimbria-fornix or as a result of an age-dependent deterioration.

UI	MeSH Term	Description	Entries
D012016	Reference Values	The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.	Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D002795	Choline O-Acetyltransferase	An enzyme that catalyzes the formation of acetylcholine from acetyl-CoA and choline. EC 2.3.1.6.	Choline Acetylase,Choline Acetyltransferase,Acetylase, Choline,Acetyltransferase, Choline,Choline O Acetyltransferase,O-Acetyltransferase, Choline
D005333	Fetus	The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN.	Fetal Structures,Fetal Tissue,Fetuses,Mummified Fetus,Retained Fetus,Fetal Structure,Fetal Tissues,Fetus, Mummified,Fetus, Retained,Structure, Fetal,Structures, Fetal,Tissue, Fetal,Tissues, Fetal
D006624	Hippocampus	A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.	Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D006651	Histocytochemistry	Study of intracellular distribution of chemicals, reaction sites, enzymes, etc., by means of staining reactions, radioactive isotope uptake, selective metal distribution in electron microscopy, or other methods.	Cytochemistry
D000109	Acetylcholine	A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.	2-(Acetyloxy)-N,N,N-trimethylethanaminium,Acetilcolina Cusi,Acetylcholine Bromide,Acetylcholine Chloride,Acetylcholine Fluoride,Acetylcholine Hydroxide,Acetylcholine Iodide,Acetylcholine L-Tartrate,Acetylcholine Perchlorate,Acetylcholine Picrate,Acetylcholine Picrate (1:1),Acetylcholine Sulfate (1:1),Bromoacetylcholine,Chloroacetylcholine,Miochol,Acetylcholine L Tartrate,Bromide, Acetylcholine,Cusi, Acetilcolina,Fluoride, Acetylcholine,Hydroxide, Acetylcholine,Iodide, Acetylcholine,L-Tartrate, Acetylcholine,Perchlorate, Acetylcholine
D000110	Acetylcholinesterase	An enzyme that catalyzes the hydrolysis of ACETYLCHOLINE to CHOLINE and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7.	Acetylcholine Hydrolase,Acetylthiocholinesterase,Hydrolase, Acetylcholine
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012688	Septum Pellucidum	A triangular double membrane separating the anterior horns of the LATERAL VENTRICLES of the brain. It is situated in the median plane and bounded by the CORPUS CALLOSUM and the body and columns of the FORNIX (BRAIN).	Septum Lucidum,Septum Pelusidum,Supracommissural Septum,Lucidum, Septum,Lucidums, Septum,Pellucidum, Septum,Pelusidum, Septum,Pelusidums, Septum,Septum Lucidums,Septum Pelusidums,Septum, Supracommissural,Septums, Supracommissural,Supracommissural Septums
D013569	Synapses	Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.	Synapse