Methylphenidate and Rosmarinus officinalis improves cognition and regulates inflammation and synaptic gene expression in

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ORIGINAL ARTICLE

Methylphenidate and Rosmarinus officinalis improves cognition and regulates inflammation and synaptic gene expression in ­AlCl3induced neurotoxicity mouse model Anibah Khalid1 · Umme Aimen Abbasi1 · Sanila Amber1 · Sumera1 · Fatima Javed Mirza1 · Muhammad Asif2 · Aneela Javed1 · Saadia Zahid1  Received: 18 March 2020 / Revised: 4 September 2020 / Accepted: 25 September 2020 © Springer Nature B.V. 2020

Abstract Methylphenidate (MPH), a psychotropic medication is commonly used for children with attention deficit hyperactivity disorder (ADHD). In this study we elucidated the neuroprotective and anti-inflammatory effects of MPH and Rosmarinus officinalis (rosemary) extract, an ancient aromatic herb with several applications in traditional medicine. Briefly, six groups of mice (n = 8 each group), were specified for the study and behavioral analysis was performed to analyze spatial memory followed by histological assessment and gene expression analysis of synaptic (Syn I, II and III) and inflammatory markers (IL-6, TNFα and GFAP) via qRT-PCR, in an A ­ lCl3-induced mouse model for neurotoxicity. The behavioral analysis demonstrated significant cognitive decline, memory defects and altered gene expression in ­AlCl3-treated group. Rosemary extract significantly decreased the expression of inflammatory and synaptic markers to the similar levels as that of MPH. The present findings suggested the neuroprotective potential of Rosmarinus officinalis extract. However, further characterization of its anti-inflammatory and neuroprotective properties and MPH is required to strategize future treatments for several neurological and neurodegenerative disorders, including Alzheimer’s disease. Keywords Methylphenidate · Rosmarinus officinalis · Neurotoxicity · Neurodegeneration · Inflammation

Introduction Methylphenidate (MPH) is a central nervous system (CNS) stimulant commonly prescribed to alleviate the symptoms of attention deficit hyperactivity disorder (ADHD). It primarily blocks the reuptake and increases the cortical levels of dopamine (DA) and norepinephrine (NE), thus defining its

Anibah Khalid and Umme Aimen Abbasi have equal contribution. Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1103​3-020-05864​-y) contains supplementary material, which is available to authorized users. * Saadia Zahid [email protected]; [email protected] 1



Department of Healthcare Biotechnology, Atta‑ur‑Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan



Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan

2

efficacy in ADHD [1, 2]. MPH is known to enhance mood, depression, anxiety, and confusion in ADHD patients while pro-long administration in doses higher than those defined for therapeutic purposes leads to MPH addiction [3]. Similar symptoms are evident in Alzheimer’s disease (AD) patients [4]. The chronic administration of MPH alters the synaptic connections by