Neonatal Reserpine Administration Produces Widespread Neuronal Losses and ⍺-Synuclein Inclusions in a Rat Model.

Publisher: Springer Country of Publication: United States NLM ID: 100929017 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-3524 (Electronic) Linking ISSN: 10298428 NLM ISO Abbreviation: Neurotox Res Subsets: MEDLINE

Publication: <2009-> : New York : Springer
Original Publication: [Amsterdam?] : Harwood Academic Publishers,

Brain/*drug effects ; Inclusion Bodies/*drug effects ; Prenatal Exposure Delayed Effects/*chemically induced ; Reserpine/*adverse effects ; alpha-Synuclein/*metabolism; Animals ; Brain/pathology ; Female ; Inclusion Bodies/pathology ; Neurons/drug effects ; Neurons/pathology ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Reserpine/administration & dosage

Historically, reserpine was widely used as an antihypertensive drug. However, severe motor and non-motor symptoms such as dyskinesia and depression led to the discontinuation of reserpine as a first-line treatment for hypertension. Reserpine functions by inhibiting vesicular monoamine transporter 2 (VMAT2), reducing sequestration of monoamines into synaptic vesicles. The consequent reduction in monoamines, most notably dopamine, serotonin and norepinephrine, in the central nervous system, causes well-defined symptoms such as catalepsy, hypoactivity and sedation in animals, and these motor and non-motor symptoms are well defined for reserpine treatment. However, no gross neuropathological changes in response to reserpine treatment have been reported previously in any animal model. In contrast, reducing VMAT2 expression in genetically modified VMAT2 LO mice leads to the production of ⍺-synuclein-positive aggregates and progressive nigrostriatal neuronal loss. These VMAT2 LO mice have reduced VMAT2 functionality during critical brain developmental stages and this could be the key to producing a reserpine model with matching histopathologies. The aim of this study was therefore to investigate the effect of neonatal reserpine administration on brain histology. We report here that a single dose of 5 mg kg ^-1 reserpine administered subcutaneously to neonatal rats on postnatal day 3 leads to widespread neuronal loss in various brain regions including the substantia nigra pars compacta, ventral tegmental area, striatum, hippocampus, locus coeruleus, amygdala and cerebral cortex, and the presence of ⍺-synuclein-positive inclusions in the substantia nigra pars compacta and the dorsal striatum within 30 days of administration.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Achor RWP, Hanson NO, Gifford RW (1955) Hypertension treated with Rauwolfia serpentina (whole root) and with reserpine. JAMA 159(9):841–845. https://doi.org/10.1001/jama.1955.02960260011004. (PMID: 10.1001/jama.1955.02960260011004)
Baloyannis SJ, Costa V, Baloyannis IS (2006) Morphological alterations of the synapses in the locus coeruleus in Parkinson’s disease. J Neurol Sci 248:35–40. https://doi.org/10.1016/j.jns.2006.05.006. (PMID: 10.1016/j.jns.2006.05.00616753180)
Bamford NS, Robinson S, Palmiter RD, Joyce JA, Moore C, Meshul CK (2004) Dopamine modulates release from corticostriatal terminals. J Neurosci 24:9541–9552. https://doi.org/10.1523/JNEUROSCI.2891-04.2004. (PMID: 10.1523/JNEUROSCI.2891-04.2004155097416730145)
Barrett CE, Hennessey TM, Gordon KM, Ryan SJ, McNair ML, Ressler KJ, Rainnie DG (2017) Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally. Mol Autism 8:42. https://doi.org/10.1186/s13229-017-0160-x. (PMID: 10.1186/s13229-017-0160-x287758275539636)
Bayer SA, Altman J (1974) Hippocampal development in the rat: cytogenesis and morphogenesis examined with autoradiography and low-level irradiation. J Comp Neurol 125:55–80. https://doi.org/10.1002/cne.901580105. (PMID: 10.1002/cne.901580105)
Berdel B, Moryś J, Maciejewska B (1997) Neuronal changes in the basolateral complex during development of the amygdala of the rat. Int J Dev Neurosci 15:755–765. https://doi.org/10.1016/s0736-5748(97)00022-1. (PMID: 10.1016/s0736-5748(97)00022-19402226)
Berman SB, Hastings TG (1999) Dopamine oxidation alters mitochondrial respiration and induces permeabiity transition in brain mitochondria: implications for Parkinson’s disease. J Neurochem 73:1127–1137. https://doi.org/10.1046/j.1471-4159.1999.0731127.x. (PMID: 10.1046/j.1471-4159.1999.0731127.x10461904)
Bertler Å (1961) Effect of reserpine on the storage of catecol amines in brain and other tissues. Acta Physiol Scand 51:75–83. https://doi.org/10.1111/j.1748-1716.1961.tb02115.x. (PMID: 10.1111/j.1748-1716.1961.tb02115.x)
Boi L, Pisanu A, Palmas MF, Fusco G, Carboni E, Casu MA, Satta V, Scherma M, Janda E, Mocci I, Mulas G, Ena A, Spiga S, Fadda P, De Simone A, Carta AR (2020) Modeling Parkinson’s disease neuropathology and symptoms by intranigral inoculation of preformed human ⍺-synuclein oligomers. Int J Mol Sci 21:8535. https://doi.org/10.3390/ijms21228535. (PMID: 10.3390/ijms212285357696693)
Bourin M (1990) Is it possible to predict the activity of a new antidepressant in animals with simple psychopharmacological tests? Fundam Clin Pharmacol 4:49–64. https://doi.org/10.1111/j.1472-8206.1990.tb01016.x. (PMID: 10.1111/j.1472-8206.1990.tb01016.x2187784)
Braak H, Ghebremedhin E, Rüb U, Bratzke H, Tredici KD (2004) Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 318:121–134. https://doi.org/10.1007/s00441-004-0956-9. (PMID: 10.1007/s00441-004-0956-915338272)
Brimblecombe KR, Vietti-Michelina S, Platt NJ, Kastli R, Hnieno A, Gracie CJ, Cragg SJ (2019) Calbindin-D28k limits dopamine release in ventral but not dorsal striatum by regulating Ca ²⁺ availability and dopamine transporter function. ACS Chem Neurosci 10:3419–3426. https://doi.org/10.1021/acschemneuro.9b00325. (PMID: 10.1021/acschemneuro.9b0032531361457)
Brodie BB, Tomich EG, Kuntzman R, Shore PA (1957) On the mechanism of action of reserpine: effect of reserpine on capacity of tissues to bind serotonin. J Pharmacol Exp Ther 119(4):461–467. (PMID: 13429453)
Carlsson A, Lindqvist M, Magnusson T (1957a) 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature 180:1200. https://doi.org/10.1038/1801200a0. (PMID: 10.1038/1801200a013483658)
Carlsson A, Rosengren E, Bertler Å, Nilsson J (1957b) Effect of reserpine on the metabolism of catechol amines. In: Garatinni S, Ghetti V (eds) Psychotropic Drugs. Elsevier (Amsterdam), pp 363–372.
Caudle WM, Richardson JR, Wang MZ, Taylor TN, Guillot TS, McCormack AL, Colebrooke RE, Di Monte DA, Emson PC, Miller GW (2007) Reduced vesicular storage of dopamine causes progressive nigrostriatal neurodegeneration. J Neurosci 27(3):8138–8148. https://doi.org/10.1523/JNEUROSCI.0319-07.2007. (PMID: 10.1523/JNEUROSCI.0319-07.2007176526046672727)
Celada P, Puig MV, Artigas F (2013) Serotonin modulation of cortical neurons and networks. Front Integr Neurosci 7:25. https://doi.org/10.3389/fnint.2013.00025. (PMID: 10.3389/fnint.2013.00025236265263630391)
Chan CS, Guzman JN, Ilijic E, Mercer JN, Rick C, Tkatch T, Meredith GE, Surmeier DJ (2007) ‘Rejuvenation’ protects neurons in mouse models of Parkinson’s disease. Nature 447:1081–1086. https://doi.org/10.1038/nature05865. (PMID: 10.1038/nature0586517558391)
Chareyron LJ, Lavenex PB, Lavenex P (2012) Postnatal development of the amygdala: a stereological study in rats. J Comp Neurol 520:3745–3763. https://doi.org/10.1002/cne.23132. (PMID: 10.1002/cne.23132)
Deutch AY, Colbran RJ, Winder DJ (2007) Striatal plasticity and medium spiny neuron dendritic remodeling in parkinsonism. Parkinsonism Relat Disord 13(Suppl 3):S251–S258. https://doi.org/10.1016/S1353-8020(08)70012-9. (PMID: 10.1016/S1353-8020(08)70012-9182672464820336)
Doyle AE, McQueen EG, Smirk FH (1955) Treatment of hypertension with reserpine, with reserpine in combination with pentapyrrolidinium, and with reserpine in combination with veratrum alkaloids. Circulation 11:170–181. https://doi.org/10.1161/01.CIR.11.2.170. (PMID: 10.1161/01.CIR.11.2.17013231254)
Erekat NS (2018) Chapter 4: Apoptosis and its role in Parkinson’s disease. In: Parkinson’s Disease: Pathogenesis and Clinical Aspects. Stoker TB, Greenland JC (eds). Codon Publications. Brisbane, Australia.
Feinstein DL, Kalinin S, Braun D (2016) Causes, consequence, and cures for neuroinflammation mediated via the locus coeruleus: noradrenergic signaling system. J Neurochem 139:154–178. https://doi.org/10.1111/jnc.13447. (PMID: 10.1111/jnc.1344726968403)
Fernandes HB, Raymond LA (2009) Chapter 2: NMDA receptors and Huntington’s disease. In: Van Dongen AM (ed) Biology of the NMDA Receptor. CRC Press/Taylor & Francis.
Fernandes VS, Santos JR, Leão AHFF, Medeiros AM, Melo TG, Izídio GS, Cabral A, Ribeiro RA, Abílio VC, Ribeiro AM, Silva RH (2012) Repeated treatment with a low dose of reserpine as a progressive model of Parkinson’s disease. Behav Brain Res 213:154–163. https://doi.org/10.1016/j.bbr.2012.03.008. (PMID: 10.1016/j.bbr.2012.03.008)
Galceran J, Miyashita-Lin EM, Devaney E, Rubenstein JL, Grosschedl R (2000) Hippocampus development and generation of dentate gyrus granule cells is regulated by LEF1. Development 127:469–482. (PMID: 10.1242/dev.127.3.469)
Gao W-J, Krimer LS, Goldman-Rakic PS (2001) Presynaptic regulation of recurrent excitation by D1 receptors in prefrontal circuits. Proc Natl Acad Sci USA 98:295–300. https://doi.org/10.1073/pnas.011524298. (PMID: 10.1073/pnas.01152429811134520)
Giorgi FS, Biagioni F, Galgani A, Pavese N, Lazzeri G, Fornai F (2020) Locus coeruleus modulates neuroinflammation in parkinsonism and dementia. Int J Mol Sci 21:8630. https://doi.org/10.3390/ijms21228630. (PMID: 10.3390/ijms212286307697920)
Glat MJ, Stefanova N, Wenning GK, Offen D (2020) Genes to treat excitotoxicity ameliorate the symptoms of the disease in mice models of multisystem atrophy. J Neural Transm (Vienna) 127:205–212. https://doi.org/10.1007/s00702-020-02158-2. (PMID: 10.1007/s00702-020-02158-2)
Hajós M, Gartside SE, Varga V, Sharp T (2003) In vivo inhibition of neuronal activity in the rat ventromedial prefrontal cortex by midbrain-raphe nuclei: role of 5-HT 1A receptors. Neuropharmacology 45:72–81. https://doi.org/10.1016/s0028-3908(03)00139-4. (PMID: 10.1016/s0028-3908(03)00139-412814660)
Hernández-López S, Tkatch T, Perez-Garci E, Galarrage E, Bargas J, Hamm H, Surmeier DJ (2000) D 2 dopamine receptors in striatal medium spiny neurons reduce L-type Ca ²⁺ currents and excitability via a novel PLCβ1-IP 3 -calcineurin-signaling cascade. J Neurosci 20:8987–8995. https://doi.org/10.1523/JNEUROSCI.20-24-08987.2000. (PMID: 10.1523/JNEUROSCI.20-24-08987.2000111249746773013)
Hess SM, Shore PA, Brodie BB (1956) Persistence of reserpine action after the disappearance of drug from brain: effect on serotonin. J Pharmacol Exp Ther 118(1):84–89. (PMID: 13368044)
Iansek R (1980) The effects of reserpine on motor activity and pallidal discharge in monkeys: implications for the genesis of akinesia. J Physiol 301:457–466. https://doi.org/10.1113/jphysiol.1980.sp013217. (PMID: 10.1113/jphysiol.1980.sp01321774114431279410)
Jellinger KA (2014) Neuropathology of multiple system atrophy: new thoughts about pathogenesis. Mov Disord 29:1720–1741. https://doi.org/10.1002/mds.26052. (PMID: 10.1002/mds.2605225297524)
Jones DC, Gunasekar PG, Borowitz JL, Isom EG (2000) Dopamine-induced apoptosis is mediated by oxidative stress and is enhanced by cyanide in differentiated PC12 cells. J Neurochem 74:2296–2304. https://doi.org/10.1046/j.1471-4159.2000.0742296.x. (PMID: 10.1046/j.1471-4159.2000.0742296.x10820189)
Khan FH, Sen T, Maiti AK, Jana S, Chatterjee U, Chakrabarti S (2005) Inhibition of rat brain mitochondrial electron transport chain activity by dopamine oxidation products during extended in vitro incubation: implications for Parkinson’s disease. Biochim Biophys Acta 1741:65–74. https://doi.org/10.1016/j.bbadis.2005.03.013. (PMID: 10.1016/j.bbadis.2005.03.01315925494)
Kline NS (1954) Use of Rauwolfia serpentina Benth. In neuropsychiatric conditions. Ann NY Acad Sci 59(1):107–132. https://doi.org/10.1111/j.1749-6632.1954.tb45922.x. (PMID: 10.1111/j.1749-6632.1954.tb45922.x13198043)
Kroeze Y, Oti M, Van Beusekom E, Cooijmans RHM, Van Bokhoven H, Kolk SM, Homberg JR, Zhou H (2017) Transcriptome analysis identifies multifaceted regulatory mechanisms dictating a genetic switch from neural network establishment to maintenance during postnatal prefrontal cortex development. Cereb Cortex 2017:1–19. https://doi.org/10.1093/cercor/bhw407. (PMID: 10.1093/cercor/bhw407)
Lee SM, Tole S, Grove E, McMahon AP (2000) A local Wnt-3a signal is required for development of the mammalian hippocampus. Development 127:457–467. (PMID: 10.1242/dev.127.3.457)
Li X, Zhu W, Roh M-S, Friedman AB, Rosborough K, Jope RS (2004) In vivo regulation of glycogen synthase kinase-3β by serotonergic activity in mouse brain. Neuropsychopharmacology 29:1426–1431. https://doi.org/10.1038/sj.npp.1300439. (PMID: 10.1038/sj.npp.130043915039769)
Lieberman OJ, McGuirt AF, Mosharov EV, Pigulevskiy I, Hobson BD, Choi S, Frier MD, Santini E, Borgkvist A, Sulzer D (2018) Dopamine trigger the maturation of striatal spiny projection neuron excitability during a critical period. Neuron 99:540–554. https://doi.org/10.1016/j.neuron.2018.06.044. (PMID: 10.1016/j.neuron.2018.06.044300572046602586)
Lugo-Candelas C, Cha J, Hong S et al (2018) Associations between brain structure and connectivity in infants and exposure to selective serotonin reuptake inhibitors during pregnancy. Jama Pediatr 172:525–533. https://doi.org/10.1001/jamapediatrics.2017.5227. (PMID: 10.1001/jamapediatrics.2017.5227296306926137537)
Masato A, Plotegher N, Boassa D, Bubacco L (2019) Impaired dopamine metabolism in Parkinson’s disease pathogenesis. Mol Neurodegeneration 14:35. https://doi.org/10.1186/s13024-019-0332-6. (PMID: 10.1186/s13024-019-0332-6)
Menzaghi F, Whelan KT, Risbrough VB, Rao TS, Lloyd GK (1997) Interactions between a novel cholinergic ion channel agonist, SIB-1765F and L-DOPA in the reserpine model of Parkinson’s disease in rats. J Pharmacol Exp Ther 280:393–401. (PMID: 8996220)
Mishra A, Singh S, Tiwari V, Parul SS (2018) Dopamine D1 receptor activation improves adult hippocampal neurogenesis and exerts anxiolytic and antidepressant-like effect via activation of WNT/β-catenin pathways in rat model of Parkinson’s disease. Neurochem Int 122:170–186. https://doi.org/10.1016/j.neuint.2018.11.020. (PMID: 10.1016/j.neuint.2018.11.02030500462)
Müller JM, Schlittler E, Bein HJ (1952) Reserpin, der sedative Wirkstoff aus Rauwolfia serpentina Benth. Experientia 8:338. https://doi.org/10.1007/BF02174406. (PMID: 10.1007/BF0217440612998611)
Murthy S, Niquille M, Hurni N, Limoni G, Frazer S, Chameau P, Van Hooft JA, Vitalis T, Dayer A (2014) Serotonin receptor 3A controls interneuron migration into the neocortex. Nat Commun 5:5524. https://doi.org/10.1038/ncomms6524. (PMID: 10.1038/ncomms652425409778)
Pan P-Y, Ryan TA (2012) Looser coupling of calcium entry and exocytosis in mid-brain dopamine neurons allows Calbindin to control release probability. Nat Neurosci 15:813–815. https://doi.org/10.1038/nn.3099. (PMID: 10.1038/nn.3099225443123703651)
Post MR, Lieberman OJ, Mosharov EV (2018) Can interactions between ⍺-synuclein, dopamine and calcium explain selective neurodegeneration in Parkinson’s disease? Front Neurosci 12:161. https://doi.org/10.3389/fnins.2018.00161. (PMID: 10.3389/fnins.2018.00161295934915861202)
Puig MV, Gulledge AT (2011) Serotonin and prefrontal cortex function: neurons, networks, and circuits. Mol Neurobiol 44:449–464. https://doi.org/10.1007/s12035-011-8214-0. (PMID: 10.1007/s12035-011-8214-0220766063282112)
Quetsch RM, Achor RWP, Litin EM, Faucett RL (1959) Depressive reactions in hypertensive patients: a comparison of those treated with Rauwolfia and those receiving no specific antihypertensive treatment. Circulation 19:366–375. https://doi.org/10.1161/01.cir.19.3.366. (PMID: 10.1161/01.cir.19.3.36613629798)
Ramaswamy S, McBride JL, Kordower JH (2007) Animal models of Huntington’s disease. ILAR J 48:356–373. https://doi.org/10.1093/ilar.48.4.356. (PMID: 10.1093/ilar.48.4.35617712222)
Sarmento-Silva AJ, Lima RH, Cabral A, Meurer Y, Ribeiro AM, Silva RH (2014) Alpha-tocopherol counteracts cognitive and motor deficits induced by repeated treatment with reserpine. Biochem Pharmacol (Los Angel) 3:153. https://doi.org/10.4172/2167-0501.1000153. (PMID: 10.4172/2167-0501.1000153)
Schubert D, Martens GJM, Kolk SM (2015) Molecular underpinnings of prefrontal cortex development in rodents provide insight into the etiology of neurodevelopmental disorders. Mol Psychiatry 20:795–809. https://doi.org/10.1038/mp.2014.147. (PMID: 10.1038/mp.2014.14725450230)
Shah R, Courtiol E, Castellanos FX, Teixeira CM (2018) Abnormal serotonin levels during perinatal development lead to behavioral deficits in adulthood. Front Behav Neurosci 12:114. https://doi.org/10.3389/fnbeh.2018.00114. (PMID: 10.3389/fnbeh.2018.00114299281945997829)
Sinclair D, Purves-Tyson TD, Allen KM, Weickert CS (2014) Impacts of stress and sex hormones on dopamine neurotransmission in the adolescent brain. Psychopharmacology 231:1581–1599. https://doi.org/10.1007/s00213-013-3415-z. (PMID: 10.1007/s00213-013-3415-z244815653967083)
Skalisz LL, Beijamini V, Joca SL, Vital MABF, Da Cunha C, Andreatini R (2002) Evaluation of the face validity of reserpine administration as an animal model of depression-Parkinson’s disease association. Prog Neuropsychopharmacol Biol Psychiatry 26:879–883. https://doi.org/10.1016/s0278-5846(01)00333-5. (PMID: 10.1016/s0278-5846(01)00333-512369260)
Stankov A, Belakaposka-Srpanova V, Bitoljanu N, Cakar L, Cakar Z, Rosoklija G (2015) Visualization of microglia with the use of immunohistochemical double staining method for CD68and Iba-1 of cerebral tissue samples in cases of brain contusions. Pril (Makedon Akad Nauk Umet Odd Za Med Nauki) 36(2):141–145. https://doi.org/10.1515/prilozi-2015-0062. (PMID: 10.1515/prilozi-2015-0062)
Stefanova N, Wenning GK (2015) Animal models of multiple system atrophy. Clin Auton Res 25:9–17. https://doi.org/10.1007/s10286-014-0266-6. (PMID: 10.1007/s10286-014-0266-6255859104412689)
Stuppy LJ, Tober JN (1955) Treatment of hypertension with reserpine (Serpasil) alone and in combination with hydralazine (Apresoline). Angiology 6(3):253–259. https://doi.org/10.1177/000331975500600308. (PMID: 10.1177/00033197550060030813275730)
Suarez LM, Alberquilla S, García-Mortes JR, Moratalla R (2018) Differential synaptic remodeling by dopamine in direct and indirect striatal projection neurons in Pitx3 ^-/- mice, a genetic model of Parkinson’s disease. J Neurosci 38(15):3619–3630. https://doi.org/10.1523/JNEUROSCI.3184-17.2018. (PMID: 10.1523/JNEUROSCI.3184-17.2018294832816705913)
Tepper JM, Sharpe NA, Koós TZ, Trent F (1998) Postnatal development of the rat neostriatum: electrophysiological, light- and electron-microscopic studies. Dev Neurosci 20:125–145. https://doi.org/10.1159/000017308. (PMID: 10.1159/0000173089691188)
Vakil RJ (1949) A clinical trial of Rauwolfia serpentina in essential hypertension. Br Heart J 11(4):350–355. https://doi.org/10.1136/hrt.11.4.350. (PMID: 10.1136/hrt.11.4.35018140347503638)
Varela-Nallar L, Inestrosa NC (2013) Wnt signaling in the regulation of adult hippocampal neurogenesis. Front Cell Neurosci 7:100. https://doi.org/10.3389/fncel.2013.00100. (PMID: 10.3389/fncel.2013.00100238050763693081)
Waldvogel HJ, Kim EH, Tippett LJ, Vonsattel J-PG, Faull RLM (2014) The neuropathology of Huntington’s disease. Curr Top Behav Neurosci 33-80. https://doi.org/10.1007/7854_2014_354.
Wilkins RW, Judson WE, Stone RW, Hollander W, Huckabee WE, Friedman IH (1954) Reserpine in the treatment of hypertension: a note on the relative dosage and effects. N Engl J Med 250(11):477–478. https://doi.org/10.1056/NEJM195403182501107. (PMID: 10.1056/NEJM19540318250110713144980)
Yan W, Wilson CC, Haring JH (1997) Effects of neonatal serotonin depletion on the development of rat dentate granule cells. Brain Res Devl Brain Res 98:177–184. https://doi.org/10.1016/s0165-3806(96)00176-9. (PMID: 10.1016/s0165-3806(96)00176-9)
Yu DX, Marchetto MC, Gage FH (2014) How to make a hippocampal dentate gyrus granule neuron. Development 141:2366–2375. https://doi.org/10.1242/dev.096776. (PMID: 10.1242/dev.09677624917496)
Zeron MM, Chen N, Moshaver A, Lee AT-C, Wellington CL, Hayden MR, Raymond LA (2001) Mutant huntingtin enhances excitotoxic cell death. Mol Cell Neurosci 17:41–53. https://doi.org/10.1006/mcne.2000.0909. (PMID: 10.1006/mcne.2000.090911161468)
Zhong P, Yuen EY, Yan Z (2008) Modulation of neuronal excitability by serotonin-NMDA interactions in the prefrontal cortex. Mol Cell Neurosci 38(2):290–299. https://doi.org/10.1016/j.mcn.2008.03.003. (PMID: 10.1016/j.mcn.2008.03.003184554312477738)
Zhou C-J, Zhao C, Pleasure SJ (2004) Wnt signaling mutants have decreased dentate granule cell production and radial glial scaffolding abnormalities. J Neurosci 24:121–126. https://doi.org/10.1523/JNEUROSCI.4071-03.2004. (PMID: 10.1523/JNEUROSCI.4071-03.2004147159456729560)

Keywords: Developmental neurotoxicity; Lewy bodies; Neuronal loss; Neuropathology; Parkinson’s disease; Reserpine

0 (alpha-Synuclein)
8B1QWR724A (Reserpine)

Date Created: 20211102 Date Completed: 20220330 Latest Revision: 20220330

20231215

10.1007/s12640-021-00434-x

34727322