Biomaterial Database

Intranigral fetal dopamine grafts induce behavioral compensation in the rat Parkinson model. 1994

G Nikkhah, and C Bentlage, and M G Cunningham, and A Björklund

Department of Medical Cell Research, University of Lund, Sweden.

Neural transplantation in experimental Parkinsonism has so far focused on the ectopic placement of fetal ventral mesencephalic (VM) neurons into the dopamine-denervated caudate-putamen. VM grafts are effective in restoring dopamine neurotransmission in the grafted caudate-putamen and in partial amelioration of behavioral deficits. Recent pharmacological and physiological data have provided strong evidence that dopamine released from dendrites of the substantia nigra pars compacta (SNc) neurons within the pars reticulata (SNr) plays an important role in the regulation of the basal ganglia output pathways. Using a novel microtransplantation approach, multiple small cell suspension grafts (250 nl) derived from the VM of E14 rat embryos were implanted into the SNr of unilaterally 6-hydroxydopamine-lesioned rats. Behavioral changes in drug-induced rotation asymmetry were monitored for up to 14 weeks postgrafting, followed by a quantitative assessment and correlation of tyrosine hydroxylase (TH)-positive cell survival. The reduction in rotational asymmetry caused by the intranigral VM grafts was 64% for SKF 38393 (D1 agonist), 54% for apomorphine (mixed D1 and D2 agonist), and 67% for quinpirole (D2 agonist) when compared to a control spinal cord graft group. By contrast, amphetamine-induced rotation was completely unaffected. The correlation between number of TH-positive cells and behavioral compensation was highest for the D1 agonist (R = -0.729), though clear-cut also for the mixed D1/D2 agonist apomorphine (R = -0.664) and the D2 agonist quinpirole (R = -0.642). Favorable morphological features of the VM micrografts included extensive migration of the dopaminergic neurons into the host SNr and the formation of dense patches of dendrite-like TH-positive terminal networks within the SNr. The results demonstrate a novel pattern of behavioral recovery induced by intranigral VM transplants in the rat Parkinson model. This may have important implications for the understanding of how the nigrostriatal dopamine system influences motor control in the basal ganglia as well as for the development of optimal transplantation strategies in Parkinson's disease.

UI	MeSH Term	Description	Entries
D008636	Mesencephalon	The middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the PONS and the DIENCEPHALON. Midbrain contains two major parts, the dorsal TECTUM MESENCEPHALI and the ventral TEGMENTUM MESENCEPHALI, housing components of auditory, visual, and other sensorimoter systems.	Midbrain,Mesencephalons,Midbrains
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010300	Parkinson Disease	A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)	Idiopathic Parkinson Disease,Lewy Body Parkinson Disease,Paralysis Agitans,Primary Parkinsonism,Idiopathic Parkinson's Disease,Lewy Body Parkinson's Disease,Parkinson Disease, Idiopathic,Parkinson's Disease,Parkinson's Disease, Idiopathic,Parkinson's Disease, Lewy Body,Parkinsonism, Primary
D004298	Dopamine	One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.	Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004873	Ergolines	A series of structurally-related alkaloids that contain the ergoline backbone structure.	Ergoline
D005260	Female		Females
D006085	Graft Survival	The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.	Graft Survivals,Survival, Graft,Survivals, Graft
D000661	Amphetamine	A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.	Desoxynorephedrin,Levoamphetamine,Phenopromin,l-Amphetamine,Amfetamine,Amphetamine Sulfate,Amphetamine Sulfate (2:1),Centramina,Fenamine,Mydrial,Phenamine,Thyramine,levo-Amphetamine,Sulfate, Amphetamine,l Amphetamine,levo Amphetamine
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
D001522	Behavior, Animal	The observable response an animal makes to any situation.	Autotomy Animal,Animal Behavior,Animal Behaviors