Metformin and fluoxetine improve depressive-like behavior in a murine model of Parkinsońs disease through the modulation of neuroinflammation, neurogenesis and neuroplasticity

Mendonça, Ingrid Prata; Paiva, Igor Henrique Rodrigues de; Duarte-Silva, Eduardo; Melo, M. T. de; Silva, Rodrigo Soares da; Oliveira, W.; Costa, Belmira da Silveira Andrade da Lara; Peixoto, Christina Alves

doi:10.1016/j.intimp.2021.108415

Cited by 24 publications

(6 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This was accompanied by a global upregulation of the anti-inflammatory marker Arg1, as well as a remarkable increase in the expression of neuroprotective and neurotrophic/growth factors, all known to exert a range of protective effects in the CNS [34]. Rotenone is known to reduce the expression of BDNF in vulnerable CNS regions [35]. This was partly seen in the hippocampus and amygdala, whereas levels were increased in the midbrain and prefrontal cortex.…”

Section: Discussionmentioning

confidence: 99%

The Anxiolytic Drug Buspirone Prevents Rotenone-Induced Toxicity in a Mouse Model of Parkinson’s Disease

Broome

Castorina

2022

IJMS

View full text Add to dashboard Cite

A pharmacological and genetic blockade of the dopamine D3 receptor (D3R) has shown to be neuroprotective in models of Parkinson’s disease (PD). The anxiolytic drug buspirone, a serotonin receptor 1A agonist, also functions as a potent D3R antagonist. To test if buspirone elicited neuroprotective activities, C57BL/6 mice were subjected to rotenone treatment (10mg/kg i.p for 21 days) to induce PD-like pathology and were co-treated with increasing dosages of buspirone (1, 3, or 10 mg/kg i.p.) to determine if the drug could prevent rotenone-induced damage to the central nervous system (CNS). We found that high dosages of buspirone prevented the behavioural deficits caused by rotenone in the open field test. Molecular and histological analyses confirmed that 10 mg/kg of buspirone prevented the degeneration of TH-positive neurons. Buspirone attenuated the induction of interleukin-1β and interleukin-6 expression by rotenone, and this was paralleled by the upregulation of arginase-1, brain-derived neurotrophic factor (BDNF), and activity-dependent neuroprotective protein (ADNP) in the midbrain, striatum, prefrontal cortex, amygdala, and hippocampus. Buspirone treatment also improved mitochondrial function and antioxidant activities. Lastly, the drug prevented the disruptions in the expression of two neuroprotective peptides, pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP). These results pinpoint the neuroprotective efficacy of buspirone against rotenone toxicity, suggesting its potential use as a therapeutic agent in neurodegenerative and neuroinflammatory diseases, such as PD.

show abstract

Section: Discussionmentioning

confidence: 99%

The Anxiolytic Drug Buspirone Prevents Rotenone-Induced Toxicity in a Mouse Model of Parkinson’s Disease

Broome

Castorina

2022

IJMS

View full text Add to dashboard Cite

show abstract

“…The common mechanism of uoxetine antidepressant is through anti-in ammatory and promotes neurogenesis [24,25,26,27]. M1-like microglia and A1-like astrocytes with neurotoxic phenotypes are often found in different brain regions of pain and depression model and serve as important sources of in ammatory factors [28,29].…”

Section: Discussionmentioning

confidence: 99%

Fluoxetine attenuates pain-like and depression-related behaviors via reducing neuroinflammation and synaptic deficits in bone cancer mice

Jiang

Yang

Qian

et al. 2022

Preprint

View full text Add to dashboard Cite

Background Bone cancer patients are often accompanied with pain and depression, which seriously affects their quality of life and survival time. Fluoxetine, a selective serotonin reuptake inhibitor, has been reported to be effective not only in reducing depression-like behaviors but also in alleviating cancer pain. However, the specific mechanisms involved remain obscure. Methods Bone cancer mice were treated with fluoxetine for 7 consecutive days after the formation of pain and depression symptoms. Neuroinflammation and synaptic changes at the basolateral amygdala (BLA) after treatment were examined with western blotting, immunofluorescence and Golgi-Cox staining. Results Compared with the tumor group, fluoxetine significantly improved the mechanical allodynia and sugar water preference ratio, and reduced the immobility time of forced swimming. In addition, we found fluoxetine had an inhibitory effect on reactive glial cells and neurotoxic glial cells of bone cancer pain (BCP) mice. Meanwhile, fluoxetine could improve synaptic function in the bone cancer mice basolateral amygdala regions. Conclusions Fluoxetine can effectively alleviate pain-like and depression-related behaviors in BCP model. The concerned mechanisms may be related to reducing neurotoxic glial cells activation and promoting synapse formation at BLA.

show abstract

“…It was able to reduce levels of phosphorylated NF-κB and iNOS. Furthermore, in combination with fluoxetine it lucratively reduced Iba-1 and GFAP levels . The novel molecule O -cyclic phytosphingosine-1-phosphate (cPS1P) is a sphingosine derivative, and it is found to be effective against neuroinflammation in PD.…”

Section: Novel Targets For Improved Pd Therapeuticsmentioning

confidence: 99%

Uncovering Novel Therapeutic Targets for Parkinson’s Disease

Soni

Delvadia

Joharapurkar

et al. 2023

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Parkinson's disease (PD) is the second most prevailing progressive disorder leading to neurodegeneration, typically in people above 65 years of age. Motor clinical manifestations of PD appear in a much later stage and include rigidity, tremors, akinesia, and gait dysfunction. There are also nonmotor symptoms like GI and olfactory dysfunction. However, they cannot be considered for diagnosis of the disease, as they are unspecific. PD pathogenesis is mainly characterized by deposits of inclusion bodies on dopaminergic (DA) neurons in substantia nigra pars compacta region (SNpc) of the brain. The major component of these inclusion bodies, are αsynuclein aggregates. α-Synuclein undergoes misfolding and oligomerization to form aggregates and fibrils. These aggregates gradually propagate PD pathology. Other prominent features of this pathological development include mitochondrial dysfunction, neuroinflammation, oxidative stress, and impaired autophagy. These all contribute to neuronal degeneration. Besides this, there are many underlying factors which influence these processes. These factors comprise molecular proteins and signaling cascades. In this review, we have listed out underexplored molecular targets that may aid in development of neoteric and advanced therapeutics.

show abstract

Metformin and fluoxetine improve depressive-like behavior in a murine model of Parkinsońs disease through the modulation of neuroinflammation, neurogenesis and neuroplasticity

Cited by 24 publications

References 56 publications

The Anxiolytic Drug Buspirone Prevents Rotenone-Induced Toxicity in a Mouse Model of Parkinson’s Disease

The Anxiolytic Drug Buspirone Prevents Rotenone-Induced Toxicity in a Mouse Model of Parkinson’s Disease

Fluoxetine attenuates pain-like and depression-related behaviors via reducing neuroinflammation and synaptic deficits in bone cancer mice

Uncovering Novel Therapeutic Targets for Parkinson’s Disease

Contact Info

Product

Resources

About