Oral methylphenidate effects on GAP43 and PSD95 expression in the developing brains of Wistar Kyoto rats

Authors

  • Patrícia Soares-Couto Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal; UCIBIO -Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050‐313 Porto, Portugal https://orcid.org/0000-0003-4714-0695
  • Vera Marisa Costa Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal; UCIBIO -Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050‐313 Porto, Portugal
  • Ana Dias-Carvalho Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal; UCIBIO -Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050‐313 Porto, Portugal
  • Susana Isabel Sá CINTESIS@RISE, Department of Biomedicine, Unit of Anatomy, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
  • Mariana Ferreira Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal; UCIBIO -Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050‐313 Porto, Portugal
  • Félix Carvalho Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal; UCIBIO -Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050‐313 Porto, Portugal
  • João Paulo Capela Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal; UCIBIO -Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050‐313 Porto, Portugal; FP-I3ID, Faculty of Health Sciences, University of Fernando Pessoa, Porto, Portugal

DOI:

https://doi.org/10.48797/sl.2024.195

Keywords:

Poster

Abstract

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neuropsychiatric disorder in childhood and adolescence [1]. Differences in brain structure, function, and connectivity were seen between ADHD and healthy individuals [2,3] but the underlying cellular and neurobiological mechanisms of ADHD are not fully understood [3,4]. Objective: To evaluate how clinically relevant oral doses of methylphenidate (MPH), a first-line ADHD treatment, affect body growth and the expression of brain proteins involved in synaptic plasticity, integrity, and neuronal growth. Methods: Wistar-Kyoto rats (18 males and 19 females) were randomly assigned to two groups. The treated group received a daily dose of MPH (5mg/kg in a 5% sucrose solution) by gavage, while the control group received an equivalent volume of 5% sucrose solution [5]. Administration began on postnatal day 15 (equivalent to childhood in humans) and lasted for 15 days, with the doses adjusted individually based on the animal’s weight (25g per 100 microL of drug or vehicle). The animal’s weight was monitored throughout the experiment. On postnatal day 30, the animals were sacrificed, the brain was dissected in separate relevant areas. Liver, heart, and kidneys were also collected. Subsequently, the brain areas were processed by Western Blotting. Results: No statistically significant changes in body and peripheral organ weight were noticed among the control and treated groups in either males or female rats. Furthermore, MPH did not affect the expression of GAP43 and PSD95 proteins in the diencephalon and prefrontal cortex. Moreover, no notable sex differences were observed for these same parameters. Conclusions: Although MPH induced no significant changes in the analyzed parameters in males, females and even no sex related changes, further investigation into new brain areas, markers, and mainly ADHD models is crucial to understand the role of MPH on development.

References

1. Banaschewski, T.; Becker K.; Döpfner, M.; Holtmann, M.; Rösler, M.; Romanos M. Attention-Deficit/Hyperactivity Disorder. Dtsch Arztebl Int. (2017) 114(9),149-59.

2. da Silva B.S.; Grevet, E.H.; Silva, L.C.F.; Ramos, J.K.N.; Rovaris, D.L.; Bau, C.H.D. An overview on neurobiology and therapeutics of attention-deficit/hyperactivity disorder. Discover Mental Health (2023) 3(1):2.

3. Posner, J.; Polanczyk, G.V.; Sonuga-Barke, E. Attention-deficit hyperactivity disorder. Lancet (2020) 395(10222):450-62.

4. Faraone, S.V.; Asherson, P.; Banaschewski, T.; Biederman, J.; Buitelaar, J.K.; Ramos-Quiroga, J.A.; et al. Attention-deficit/hyperactivity disorder. Nat Rev Dis Primers (2015) 1:15020.

5. Loureiro-Vieira, S.; Costa, V.M.; Duarte, J.A.; Duarte-Araújo, M.; Gonçalves-Monteiro, S.; Maria de Lourdes, B.; et al. Methylphenidate clinically oral doses improved brain and heart glutathione redox status and evoked renal and cardiac tissue injury in rats. Biomed Pharmacother (2018) 100:551-63.

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Published

2024-05-01

How to Cite

Soares-Couto, P., Costa, V. M., Dias-Carvalho, A., Sá, S. I., Ferreira, M., Carvalho, F., & Capela, J. P. (2024). Oral methylphenidate effects on GAP43 and PSD95 expression in the developing brains of Wistar Kyoto rats. Scientific Letters, 1(Sup 1). https://doi.org/10.48797/sl.2024.195

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