TY - JOUR
T1 - Heterogeneity of melanized neurons expressing neurotensin receptor messenger RNA in the substantia nigra and the nucleus paranigralis of control and Parkinson's disease brain
AU - Yamada, M.
AU - Yamada, M.
AU - Richelson, E.
N1 - Funding Information:
Human brain tissuesw ere obtained fromM ayo Clinic JacksonvilleB rain Bank (JacksonvilleF, L, supportedin part by NationalI nstituteo n Aging), Medical Pathology, Mayo Clinic (RochesterM, N) and NationalN eurological ResearchS pecimenB ank,V eteranAs ffairsM edicalC enter (Los Angeles, CA, supported bNy ational Instituteo f NeurologicaDl isordersa nd Stroke/NationaInl stituteo f MentalH ealth,N ationaMl ultipleS clerosisS ocietyH, eredi-tary Disease FoundationC, omprehensivEep ilepsy Program, Tourette SyndromAses ociationD, ystoniaM edical ResearchF oundationa nd VeteransH ealth Servicesa nd ResearcAh dministrationD,e partmenotf VeteranAs ffairs). The diagnosiso f Parkinson'ds iseasew as madec linically and additionahl istopathologicdaila gnosisw as verifieda t NationalN eurologicaRl esearchS pecimenB ank. Table 1 summarizetsh e sourceso f humanb raint issueu sedfor in situ hybridizationT. he midbrains ectionsw ere obtained from foucr ontrosl ubject(st hreem alesa ndo nef emalea, ged 57 80,p ost mortem delay2 0 26.5h ) and four Parkinson's diseasep atient(sf ourm alesa, ged 79-80po, st mortem delay 5-21.5h ). The sampleso f the heado f the caudaten ucleus, putamenw ere obtainedfr om threec ontrols ubjects( two males and one female,a ged 57-80, post mortem delay 20-26.5h ). The sampleso f nucleusa ccumbenws ere ob-tainedf romtwo controls ubject(so ne malaen done female, aged5 7~58p, ost mortem delay2 ff 26.25h ). The brainsw ere fixed in 20% (w/v) sucrose4, % (w:v) paraformaldehyidne 0 .1 M phosphatbeu ffer( pH 7.2) for two days. After the fixation and cryoprotectiont,h e brains were sectioneda t a thicknesso f 25/~mu sing a sliding microtomeo r cryostat.F ree floatingc oronalsec-tions were fixed again with 4% (w/v) paraformaldehyde in 0.1 M phosphateb uffer overnighta nd processedfo r in situ hybridization.
Funding Information:
Acknowledgements--The authors thankP rof. W. W. Tourtellottef rom the National Neurological Research SpecimenB ank for kindly supplyingt he brain samples. We thank Dr P. J. Isackson, Dr M. Mckinney and Dr C. Bolden-Watsofno r their help wiitnh situ hybridization histochemistryD, r K. Sugaya for helpful dis- cussions,D r J. Takeuchi for continuouse ncouragement and Mr M. A. Watson and Miss N. J. Coleman for excellentt echnicala ssistanceT. his work was supported by the Mayo Foundation,S anaruko Neuro-psychiatric Hospital and Grant MH 27692 from the U.S.P.H.S. (N.I.M.H.).
PY - 1995/1
Y1 - 1995/1
N2 - We have recently cloned the neurotensin receptor from human substantia nigra. Using in situ hybridization techniques, with an 35S-labeled antisense RNA probe complementary to this receptor complementary DNA, we studied the expression of the human neurotensin receptor in the brain from control and Parkinson's disease subjects. We also performed an analogous study with rat brain. Neurotensin receptor messenger RNA was present in high levels in melanized neurons of the substantia nigra pars compacta and the nucleus paranigralis (the ventral tegmental area for rat brain). Background levels of signals for neurotensin receptor messenger RNA were detected in the nucleus ruber, the colliculus inferior and the striatal subdivisions (the nucleus caudatus, the putamen and the nucleus accumbens) of both human and rat brain. All these areas, except the nucleus ruber and the collicus inferior, contain very high to high levels of neurotensin receptor binding sites. Additionally, Parkinson's disease brains had markedly fewer melanized (possibly dopaminergic) neurons, as expected, and correspondingly very low or background levels of messenger RNA for neurotensin receptor. We have also demonstrated heterogeneity among the melanized cells expressing messenger RNA encoding the neurotensin receptor in the substantia nigra and the nucleus paranigralis of human brain. The neurons in the nucleus paranigralis had lower melanin pigmentation and higher expression of neurotensin receptor messenger RNA. In general, the expression of the messenger RNA within the highly and evenly melanized neurons was lower than that found in low or unevenly pigmented neurons. The neurons in the nucleus paranigralis had lower melanin pigmentation and higher expression of neurotensin receptor messenger RNA. The low pigmented neurons in the ventral tier of the substantia nigra had relatively high expression. On the other hand, highly and evenly melanized neurons in these regions of the brain had low expression of neurotensin receptor messenger RNA. Together with the previous binding data, it is suggested that not only in rat brain, but also in human brain, melanized (possibly dopaminergic) neurons in the substantia nigra and the nucleus paranigralis (ventral tegmental area of rat brain) synthesize neurotensin receptors and express them in their perikarya and the terminal regions. Additionally, the heterogeneity of the melanized neurons in human brain may play a role in the normal function of dopaminergic systems and probably in the etiology of some neurological and psychiatric disorders.
AB - We have recently cloned the neurotensin receptor from human substantia nigra. Using in situ hybridization techniques, with an 35S-labeled antisense RNA probe complementary to this receptor complementary DNA, we studied the expression of the human neurotensin receptor in the brain from control and Parkinson's disease subjects. We also performed an analogous study with rat brain. Neurotensin receptor messenger RNA was present in high levels in melanized neurons of the substantia nigra pars compacta and the nucleus paranigralis (the ventral tegmental area for rat brain). Background levels of signals for neurotensin receptor messenger RNA were detected in the nucleus ruber, the colliculus inferior and the striatal subdivisions (the nucleus caudatus, the putamen and the nucleus accumbens) of both human and rat brain. All these areas, except the nucleus ruber and the collicus inferior, contain very high to high levels of neurotensin receptor binding sites. Additionally, Parkinson's disease brains had markedly fewer melanized (possibly dopaminergic) neurons, as expected, and correspondingly very low or background levels of messenger RNA for neurotensin receptor. We have also demonstrated heterogeneity among the melanized cells expressing messenger RNA encoding the neurotensin receptor in the substantia nigra and the nucleus paranigralis of human brain. The neurons in the nucleus paranigralis had lower melanin pigmentation and higher expression of neurotensin receptor messenger RNA. In general, the expression of the messenger RNA within the highly and evenly melanized neurons was lower than that found in low or unevenly pigmented neurons. The neurons in the nucleus paranigralis had lower melanin pigmentation and higher expression of neurotensin receptor messenger RNA. The low pigmented neurons in the ventral tier of the substantia nigra had relatively high expression. On the other hand, highly and evenly melanized neurons in these regions of the brain had low expression of neurotensin receptor messenger RNA. Together with the previous binding data, it is suggested that not only in rat brain, but also in human brain, melanized (possibly dopaminergic) neurons in the substantia nigra and the nucleus paranigralis (ventral tegmental area of rat brain) synthesize neurotensin receptors and express them in their perikarya and the terminal regions. Additionally, the heterogeneity of the melanized neurons in human brain may play a role in the normal function of dopaminergic systems and probably in the etiology of some neurological and psychiatric disorders.
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U2 - 10.1016/0306-4522(94)00395-L
DO - 10.1016/0306-4522(94)00395-L
M3 - Article
C2 - 7700529
AN - SCOPUS:0028812406
SN - 0306-4522
VL - 64
SP - 405
EP - 417
JO - Neuroscience
JF - Neuroscience
IS - 2
ER -