Neurons exhibiting dopamine D2 receptor immunoreactivity in the substantia nigra of the mutant weaver mouse. 1999

S G Xu, and C Prasad, and D E Smith
Department of Cell Biology and Anatomy, LSU Medical Center, New Orleans, LA 70112, USA.

Neurons exhibiting D2 receptor-like immunoreactivity were investigated in the substantia nigra pars compacta of weaver mice at the light and electron microscope levels using immunocytochemical techniques. At the light microscope level, there was significant loss of D2-like immunoreactive cells in weaver mice and the remaining labeled cells exhibited less intense immunoreactivity. At the ultrastructural level, there was a decrease in the number of immunoreactive profiles and fewer synapses were observed abutting labeled dendritic profiles. In addition, degenerative changes were noted in some of the D2 receptor-like immunoreactive profiles. Double labeling with D2 and tyrosine hydroxylase indicated that the majority of the labeled profiles were double labeled. Eight-week-old homozygous weavers were paired with wild-type littermates as controls and perfused with a buffered solution of acrolein/paraformadehyde. Midbrain sections were reacted immunocytochemically either with an antiserum to D2 or with antisera to D2 and tyrosine hydroxylase, using a double-labeling technique. Sections were processed for light and electron microscopy by standard methods. The results of this study confirm the autoreceptor-like activity of D2 receptors on nigral dopamine neurons. The cell degeneration, down-regulation of D2 receptors, and decreased dendritic and synaptic components in the neuropil suggest that the synaptic integrity of the substantia nigra has been compromised, which in turn would affect the functional efficacy of the basal ganglia circuitry. This altered circuity is expressed in the Parkinson-like symptoms displayed by this mutant mouse.

UI MeSH Term Description Entries
D008818 Mice, Neurologic Mutants Mice which carry mutant genes for neurologic defects or abnormalities. Lurcher Mice,Nervous Mice,Reeler Mice,Staggerer Mice,Weaver Mice,Chakragati Mice,Chakragati Mouse,Lurcher Mouse,Mice, Neurological Mutants,Mouse, Neurologic Mutant,Mouse, Neurological Mutant,Nervous Mouse,Neurologic Mutant Mice,Neurological Mutant Mouse,Reeler Mouse,Staggerer Mouse,Weaver Mouse,ckr Mutant Mice,Mice, Chakragati,Mice, Lurcher,Mice, Nervous,Mice, Neurologic Mutant,Mice, Reeler,Mice, Staggerer,Mice, Weaver,Mice, ckr Mutant,Mouse, Chakragati,Mouse, Lurcher,Mouse, Nervous,Mouse, Reeler,Mouse, Staggerer,Mouse, Weaver,Mutant Mice, Neurologic,Mutant Mice, ckr,Mutant Mouse, Neurologic,Neurologic Mutant Mouse
D008854 Microscopy, Electron Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen. Electron Microscopy
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
D003712 Dendrites Extensions of the nerve cell body. They are short and branched and receive stimuli from other NEURONS. Dendrite
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
D013378 Substantia Nigra The black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce DOPAMINE, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored MELANIN is a by-product of dopamine synthesis. Nigra, Substantia,Nigras, Substantia,Substantia Nigras
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
D014446 Tyrosine 3-Monooxygenase An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC 1.14.16.2. Tyrosine Hydroxylase,3-Monooxygenase, Tyrosine,Hydroxylase, Tyrosine,Tyrosine 3 Monooxygenase
D016923 Cell Death The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. Death, Cell

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