Study of the Effects of L-tryptophane Nanoparticles on Motor Behavior in Alzheimer's Experimental Models

Author(s): Andressa L. Miri*, Andressa P. Hosni, Jossinelma C. Gomes, Rubiana M. Mainardes, Najeh M. Khalil, Rossana G. del J.V. Marcano, Mário C. da S. Pereira, Ivo I. Kerppers.

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 18 , Issue 1 , 2019

Submit Manuscript
Submit Proposal

Graphical Abstract:


Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive and incapacitating decay of cognitive, neuropsychiatric, and behavioral manifestations. L-tryptophan is the precursor amino acid of serotonin, which is a neurotransmitter responsible for mood balance and the sense of well-being and can be administered in the form of nanoparticles. Objective: This study analyzed the effectiveness of L-tryptophan nanoparticles and L-tryptophan on behavioral physiological alterations resulting from AD in animal models.

Methods: The sample consisted of 50 Rattus norvegicus rats, divided in 10 groups with 5 animals each: one negative control (NC), three positive control groups (C3, C7, and C21), three groups treated with L-tryptophan nanoparticles (T3N, T7N, and T21N) at the concentration of 1.5 mg, and three groups treated with L-tryptophan (T3L, T7L, and T21L) at the concentration of 1.5 mg. The rats underwent stereotactic surgery to induce AD through the injection of amyloid beta-amyloid peptide1-42 in the intracerebroventricular region. All rats were submitted to pre- and post-surgery and post-treatment motor behavior evaluation through the Later Water Maze (LWM) and elevated cross-labyrinth (ECL). Histological analysis was performed to verify the presence of senile plaques, and the statistical analysis used the unpaired T-test.

Results: Significant intergroup differences were observed in some of the evaluated parameters between treated and untreated groups.

Conclusion: It was concluded that the treatment with L-tryptophan nanoparticles was beneficial to improve behavioral reactions in the Alzheimer's model.

Keywords: Dementia, serotonin, neuroinflammation, neurodegeneration, neuroscience, nanoscience.

Geda YE, Schneider LS, Gitlin LN, et al. Sintomas neuropsiquiátricos na doença de Alzheimer: Progresso passado e antecipação do futuro. Alzheimers Dement 2013; 9(5): 602-8.
Silagi ML, Bertoluccill PH, Ortizl KZ. Naming ability in patients with mild to moderate Alzheimer’s disease: What changes occur with the evolution of the disease? Clinics 2015; 70: 6.
Fichman HC, Oliveira RM, Fernandes CS. Neuropsychological and neurobiological markers of the preclinical stage of Alzheimer’s disease. Psychol Neurosci 2011; 4(2): 245-53.
Holtzman DM, Morris JC, Goate AM. Doença de Alzheimer: O desafio do segundo século. Medicina de tradução científica. 2017; 3: 77.
Frota NAF, Nitrini R, Forlenza O, et al. Critérios para o diagnóstico de doença de Alzheimer. Dement Neuropsychol 2011; 5(1): 5-10.
Studart NA, Nitrini R. Subjective cognitive decline: The first clinical manifestation of Alzheimer’s disease? Dement Neuropsychol 2016; 10(3): 170-7.
Fukushima RLM, Carmo EG. Pedroso R do V, Micali PN, Viola J, Fuzaro JG. Effects of cognitive stimulation on neuropsychiatric symptoms in elderly with Alzheimer’s disease: A systematic review. Dement Neuropsychol 2016; 10(3): 178-84.
Medeiros GE de, Rosas BO, Lessa A de SN. Perfil nutricional de idosos portadores de Alzheimer atendidos em home care. Rev Bras Neurol 2016; 52(4): 5-17.
Mestres MC, Morris JC, Roe CM. Sintomas “não cognitivos” da doença de Alzheimer precoce: Uma análise longitudinal. Neurologia 2015; 84(6): 617-22.
Ringman JM, Liang LJ, Zhou Y, et al. Mudanças precoce no comportamento da doença de Alzheimer familiar na rede de Alzheimer, hereditária. Cérebro 2015; 138(4): 1036-45.
Trillo L, Das D, Hsieh W, et al. Alterações ascendentes dos sistemas monoaminérgicos na doença de Alzheimer. Traduzindo ciências básicas em cuidados clínicos. Neurosci Biobehav Rev 2013; 37(8): 1363-79.
Vermeiren Y, Van Dam D, Aerts T, Engelborghs S, De Deyn PP. Alterações do neurotransmissor monoaminérgico nas regiões do cérebro pós-morte de pacientes deprimidos e agressivos com doença de Alzheimer. Envelhecimento Neurobiol 2014; 35(12): 2691-700.
Mossello E, Boncinelli M, Caleri V, et al. O tratamento antidepressivo associado ao declínio cognitivo reduzido na doença de Alzheimer? Dement Geriatr Cogn Disord 2008; 25: 372-9.
Walther DJ, Bader M. Uma isoforma central de hidroxilase de triptofano central. Biochem Pharmacol 2003; 66: 1673-80.
Muzerelle A, Scotto-Lomassese S, Bernard JF, Soiza-Reilly M, Gaspar P. O rastreamento anterógrado condicional revela alvos distintos de grupos de células de serotonina individuais (B5-B9) para o prosencéfalo e tronco encefálico. Brain Struct Funct 2016; 221: 535-61.
Albert PR, Ansari FV, Luckhart C. Serotonin-prefrontal cortical circuitry in anxiety and depression phenotypes: Pivotal role of pre- and post-synaptic 5-HT1A receptor expression. Front Behav Neurosci 2014; 8: 199.
Jenkins TA, Nguyen JCD, Polglaze KE, Bertrand PP. Influence of tryptophan and serotonin on mood and cognition with a possible role of the gut-brain axis. Nutrients 2016; 8(1): 56.
Mattos AC, Altmeyer C, Tominaga TT, Khalil NM, Mainardes RM. Polymeric nanoparticles for oral delivery of 5-fluorouracil: Formulation optimization, cytotoxicity assay and pre-clinical pharmacokinetics study. Eur J Pharm Sci 2016; 10(84): 83-91.
Antônio E, Antunes ODR. Junior, De Araújo IS, Khalil NM, Mainardes RM. Poly (lactic acid) nanoparticles loaded with ursolic acid: Characterization and in vitro evaluation of radical scavenging activity and cytotoxicity. Mater Sci Eng C Mater Biol Appl 2017; 71: 156-66.
Glikmann-Johnston Y, Saling MM, Reutens DC, Stout JC. Hippocampal 5-HT1A receptor and spatial learning and memory. Front Pharmacol 2015; 6: 289.
Miri AL, Hosni AP, Gomes JC, Kerppers II, Pereira MCS. Study of L-Tryptophan in an experimental model of depression caused by Alzheimer’s Disease. J Phisycal Edu 2017; 28: 1-8.
Mathew A, Fukuda T, Nagaoka Y. Curcumin loaded-PLGA nanoparticles conjugated with Tet-1 peptide for potential use in Alzheimer’s disease. PLoS One 2012; 7(3): e32616.
Lockman PR, Koziara JM, Mumper RJ, Allen DD. Nanoparticle surface charges alter blood-brain barrier integrity and permeability. J Drug Target 2004; 12: 635-1.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [44 - 51]
Pages: 8
DOI: 10.2174/1871527317666181105111157
Price: $58

Article Metrics

PDF: 17
PRC: 1