Targeting Oxidative Stress, Mitochondrial Dysfunctions and Neuroinflammation as Therapeutic Strategies for Psychiatric and Neurological Disorders

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (20 May 2023) | Viewed by 5858

Special Issue Editors


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Guest Editor
Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, 09124 Cagliari, CA, Italy
Interests: neurosteroids; neuroactive steroids; cannabinoids; neuropsychiatric disorders; schizophrenia; bipolar disorders; sleep deprivation; Parkinson’s disease
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Guest Editor
Department of Pharmacological and Biomolecular Sciences, University of Milano, Via Balzaretti 9, 20133 Milan, Italy
Interests: neuroactive steroids; finasteride; antidepressants; diabetes mellitus; sex differences

Special Issue Information

Dear Colleagues,

Converging clinical and preclinical evidence documents that oxidative stress plays a critical role in the etiopathogenesis of psychiatric and neurological disorders. Mitochondria are a major source and target of reactive oxygen species (ROS) triggered by intense bioenergetic processes within cells, including neurons and glia.

Imbalances in neuronal redox status towards the excessive production of ROS as side products lead to the hyperactivation of astrocytes and microglia, resulting in the enhancement of ROS generation and the overactivation of inflammatory pathways. In numerous clinical studies, markers of oxidative stress are elevated in patients with neuropsychiatric disorders, and antioxidant treatment has provided promising results in the management of both psychiatric and neurological symptoms, either as monotherapy or adjunctive therapy. For example, through its antioxidant effects, the reduction of cytokine activity, the modulation of dopamine and glutamate transmission, and the reversal of mitochondrial dysfunction, the acetylated precursor of L-cysteine (N-acetyl-L-cysteine) has shown therapeutic properties for the treatment of multiple psychiatric disorders, including schizophrenia, anxiety, and substance-use disorders (SUDs). Similarly, thanks to its marked anti-inflammatory and antioxidant properties, the broad-spectrum antibiotic minocycline has been proposed as an adjuvant treatment for neurodegenerative and psychiatric diseases featuring an inflammatory basis. On the other hand, aberrant inflammatory markers have been linked to poor response to antidepressant medications, and numerous clinical trials have documented a positive correlation between antipsychotic efficacy and restoration of the imbalance of pro- and anti-inflammatory cytokine levels in patients with schizophrenia.

The aim of this Special Issue is to collect research and/or review articles that may help to understand the complex interplay among oxidative stress, mitochondrial dysfunction, and neuroinflammation in the pathophysiology of neuropsychiatric disorders, with the final goal of introducing novel therapeutic intervention strategies. We especially welcome the submission of articles focusing on the role of genetic and non-genetic risk factors (environmental pollutants, bad lifestyle habits, food contaminants, obesity) on the pathological crosstalk between ROS and inflammation in the CNS.

Dr. Roberto Frau
Dr. Silvia Giatti
Guest Editors

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Keywords

  • superoxide
  • hydroxyl radical
  • hydrogen peroxide
  • antioxidant
  • neuropsychiatric disorders
  • schizophrenia
  • bipolar disorders
  • glial cells
  • astrocytes
  • N-Acetylcysteine
  • minocycline
  • antidepressants
  • antipsychotics
  • neuroprotective agents
  • anti-inflammatory drugs

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Published Papers (2 papers)

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Research

22 pages, 3378 KiB  
Article
Three-Dimensional Analysis of Sex- and Gonadal Status- Dependent Microglial Activation in a Mouse Model of Parkinson’s Disease
by Amandine Isenbrandt, Katherine Coulombe, Marc Morissette, Mélanie Bourque, Jérôme Lamontagne-Proulx, Thérèse Di Paolo and Denis Soulet
Pharmaceuticals 2023, 16(2), 152; https://doi.org/10.3390/ph16020152 - 20 Jan 2023
Cited by 5 | Viewed by 2124
Abstract
Parkinson’s disease (PD) is characterized by neurodegeneration and neuroinflammation. PD prevalence and incidence are higher in men than in women and modulation of gonadal hormones could have an impact on the disease course. This was investigated in male and female gonadectomized (GDX) and [...] Read more.
Parkinson’s disease (PD) is characterized by neurodegeneration and neuroinflammation. PD prevalence and incidence are higher in men than in women and modulation of gonadal hormones could have an impact on the disease course. This was investigated in male and female gonadectomized (GDX) and SHAM operated (SHAM) mice. Dutasteride (DUT), a 5α-reductase inhibitor, was administered to these mice for 10 days to modulate their gonadal sex hormones. On the fifth day of DUT treatment, mice received 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to model PD. We have previously shown in these mice the toxic effect of MPTP in SHAM and GDX males and in GDX females on dopamine markers and astrogliosis whereas SHAM females were protected by their female sex hormones. In SHAM males, DUT protected against MPTP toxicity. In the present study, microglial density and the number of doublets, representative of a microglial proliferation, were increased by the MPTP lesion only in male mice and prevented by DUT in SHAM males. A three-dimensional morphological microglial analysis showed that MPTP changed microglial morphology from quiescent to activated only in male mice and was not prevented by DUT. In conclusion, microgliosis can be modulated by sex hormone-dependent and independent factors in a mice model of PD. Full article
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17 pages, 3030 KiB  
Article
Piracetam as a Therapeutic Agent for Doxorubicin-Induced Cognitive Deficits by Enhancing Cholinergic Functions and Reducing Neuronal Inflammation, Apoptosis, and Oxidative Stress in Rats
by Vasudevan Mani, Syed Imam Rabbani, Ali Shariq, Palanisamy Amirthalingam and Minhajul Arfeen
Pharmaceuticals 2022, 15(12), 1563; https://doi.org/10.3390/ph15121563 - 14 Dec 2022
Cited by 11 | Viewed by 3089
Abstract
Cancer chemotherapy is known to cause cognitive defects in patients. Our study investigated the effect of piracetam (PIRA; 200 or 400 mg/kg) against doxorubicin (DOX)-induced cognitive deficits in a rat model. The cognitive parameters were analyzed using elevated plus-maze, novel object recognition, and [...] Read more.
Cancer chemotherapy is known to cause cognitive defects in patients. Our study investigated the effect of piracetam (PIRA; 200 or 400 mg/kg) against doxorubicin (DOX)-induced cognitive deficits in a rat model. The cognitive parameters were analyzed using elevated plus-maze, novel object recognition, and Y-maze tests. Acetylcholinesterase (AChE), neuroinflammatory mediators (cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nuclear factor-κB (NF-κB), tumor necrosis factor-alpha (TNF-α)), apoptotic proteins (B-cell lymphoma-2 (Bcl-2), Bcl2 associated X protein (Bax), cysteine aspartate specific protease-3 (caspase-3)), oxidative parameters (malondialdehyde (MDA), catalase (CAT), and glutathione (GSH)) were also determined in the brain. PIRA administration offered significant protection against DOX-induced cognitive deficits in all maze tests and restored cholinergic functions via a significant reduction in AChE levels. Additionally, PIRA suppressed DOX-induced neuroinflammatory mediators (COX-2, PGE2, NF-κB, and TNF-α), pro-apoptotic proteins (Bax and caspase-3), and oxidative stress (MDA). Besides, it facilitated antioxidant (CAT and GSH) levels. Hence, our study highlighted that the neuroprotective activity of PIRA against DOX-induced cognitive deficits can be linked to reductions of AChE levels, neuro-inflammatory mediators, pro-apoptotic proteins, and oxidative stress. Full article
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