Biomaterial Database

An animal model for coexisting tardive dyskinesia and tardive parkinsonism: a glutamate hypothesis for tardive dyskinesia. 1993

L M Gunne, and P E Andrén

Department of Psychiatry, Ulleråker, Uppsala University, Sweden.

There is now ample evidence for long-term malfunctioning within five different brain GABAergic pathways in a monkey model for tardive dyskinesia (TD). Three of these GABA connections (GPe-STN, CP-SNr, and CP-GPi) are chronically downregulated during neuroleptic treatment and after some years they do not seem to regain their normal activity, even when the neuroleptics are discontinued. The persistent downregulation of these three GABA connections, evidenced by depressions of terminal GAD activity and GABA levels, appears to be a conceivable mechanism behind tardive parkinsonism (TP), often reported to coexist with TD in the clinic. The TD patients' well-known lack of awareness of their symptoms may be due to their parkinsonian "sensory neglect." Another two GABA malfunctioning connections were found in our monkey model: SNr-VA/VL and GPi-VA/VL. These pathways are upregulated during chronic neuroleptic treatment, partly due to an elevated glutamate release within subthalamofugal pathways. This chronic glutamatergic hyperactivity may have acted via an excitotoxic mechanism and consequently both GPi and VA/VL had a low synaptic activity in our dyskinetic monkeys, as measured by 2-deoxyglucose uptake, even 4 months after the last neuroleptic dose. It is hypothesized that TD may be due to an excitotoxic lesion of the inhibitory GABAergic VA/VL afferents, while TP has to do with persistent malfunctioning of downregulated SNr and GPi afferents.

UI	MeSH Term	Description	Entries
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
D001923	Brain Chemistry	Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.	Chemistry, Brain,Brain Chemistries,Chemistries, Brain
D002428	Cebus	A genus of the family CEBIDAE, subfamily CEBINAE, consisting of gracile or untufted capuchin species. Tufted capuchins belong to genus SAPAJUS. Members include C. capucinus, C. nigrivultatus, and C. albifrons. Cebus inhabits the forests of Central and South Americas.	Cebu,Gracile Capuchins,Monkey, Capuchin,Monkey, Ring-Tail,Monkey, Ringtail,Monkey, Ringtailed,Untufted Capuchins,White-Fronted Capuchin,Monkey, Ring-Tailed,Capuchin Monkey,Capuchin Monkeys,Capuchin, Gracile,Capuchin, Untufted,Capuchin, White-Fronted,Gracile Capuchin,Monkey, Ring Tail,Monkey, Ring Tailed,Ring-Tail Monkey,Ring-Tail Monkeys,Ring-Tailed Monkey,Ring-Tailed Monkeys,Ringtail Monkey,Ringtail Monkeys,Ringtailed Monkey,Ringtailed Monkeys,Untufted Capuchin,White Fronted Capuchin,White-Fronted Capuchins
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
D004409	Dyskinesia, Drug-Induced	Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)	Dyskinesia, Medication-Induced,Medication-Induced Dyskinesia,Drug-Induced Dyskinesia,Drug-Induced Dyskinesias,Dyskinesia, Drug Induced,Dyskinesia, Medication Induced,Dyskinesias, Drug-Induced,Dyskinesias, Medication-Induced,Medication Induced Dyskinesia,Medication-Induced Dyskinesias
D005680	gamma-Aminobutyric Acid	The most common inhibitory neurotransmitter in the central nervous system.	4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
D005968	Glutamate Decarboxylase	A pyridoxal-phosphate protein that catalyzes the alpha-decarboxylation of L-glutamic acid to form gamma-aminobutyric acid and carbon dioxide. The enzyme is found in bacteria and in invertebrate and vertebrate nervous systems. It is the rate-limiting enzyme in determining GAMMA-AMINOBUTYRIC ACID levels in normal nervous tissues. The brain enzyme also acts on L-cysteate, L-cysteine sulfinate, and L-aspartate. EC 4.1.1.15.	Glutamate Carboxy-Lyase,Glutamic Acid Decarboxylase,Acid Decarboxylase, Glutamic,Carboxy-Lyase, Glutamate,Decarboxylase, Glutamate,Decarboxylase, Glutamic Acid,Glutamate Carboxy Lyase
D005971	Glutamates	Derivatives of GLUTAMIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure.	Glutamic Acid Derivatives,Glutamic Acids,Glutaminic Acids
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
D018698	Glutamic Acid	A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.	Aluminum L-Glutamate,Glutamate,Potassium Glutamate,D-Glutamate,Glutamic Acid, (D)-Isomer,L-Glutamate,L-Glutamic Acid,Aluminum L Glutamate,D Glutamate,Glutamate, Potassium,L Glutamate,L Glutamic Acid,L-Glutamate, Aluminum