Atorvastatin ameliorates depressive behaviors and neuroinflammatory in streptozotocin-induced diabetic mice

Zhang, Haina; Yu, Xu-Ben; Tang, Congrong; Cao, Yancheng; Yang, Fan; Xu, Lei-Mei; Sun, Ryan; Ye-Zi,; Wang, Ye-Xuan; Liang, Jing

doi:10.1007/s00213-019-05406-w

Cited by 18 publications

(12 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, Na and colleagues reported that administration of atorvastatin to streptozotocin-induced diabetic mice rescued depressive behaviors, attenuated microglial activation in the prefrontal cortex, and reduced the expression of IL-1β, TNF-α, and NF-κB p65 expression in the prefrontal cortex. Overall, the data in animal models supports that statins reduce stress induced depression through amelioration of inflammation (169).…”

Section: Statinsmentioning

confidence: 65%

Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories

Hassamal

2023

Front. Psychiatry

105

View full text Add to dashboard Cite

In a subset of patients, chronic exposure to stress is an etiological risk factor for neuroinflammation and depression. Neuroinflammation affects up to 27% of patients with MDD and is associated with a more severe, chronic, and treatment-resistant trajectory. Inflammation is not unique to depression and has transdiagnostic effects suggesting a shared etiological risk factor underlying psychopathologies and metabolic disorders. Research supports an association but not necessarily a causation with depression. Putative mechanisms link chronic stress to dysregulation of the HPA axis and immune cell glucocorticoid resistance resulting in hyperactivation of the peripheral immune system. The chronic extracellular release of DAMPs and immune cell DAMP-PRR signaling creates a feed forward loop that accelerates peripheral and central inflammation. Higher plasma levels of inflammatory cytokines, most consistently interleukin IL-1β, IL-6, and TNF-α, are correlated with greater depressive symptomatology. Cytokines sensitize the HPA axis, disrupt the negative feedback loop, and further propagate inflammatory reactions. Peripheral inflammation exacerbates central inflammation (neuroinflammation) through several mechanisms including disruption of the blood–brain barrier, immune cellular trafficking, and activation of glial cells. Activated glial cells release cytokines, chemokines, and reactive oxygen and nitrogen species into the extra-synaptic space dysregulating neurotransmitter systems, imbalancing the excitatory to inhibitory ratio, and disrupting neural circuitry plasticity and adaptation. In particular, microglial activation and toxicity plays a central role in the pathophysiology of neuroinflammation. Magnetic resonance imaging (MRI) studies most consistently show reduced hippocampal volumes. Neural circuitry dysfunction such as hypoactivation between the ventral striatum and the ventromedial prefrontal cortex underlies the melancholic phenotype of depression. Chronic administration of monoamine-based antidepressants counters the inflammatory response, but with a delayed therapeutic onset. Therapeutics targeting cell mediated immunity, generalized and specific inflammatory signaling pathways, and nitro-oxidative stress have enormous potential to advance the treatment landscape. Future clinical trials will need to include immune system perturbations as biomarker outcome measures to facilitate novel antidepressant development. In this overview, we explore the inflammatory correlates of depression and elucidate pathomechanisms to facilitate the development of novel biomarkers and therapeutics.

show abstract

Section: Statinsmentioning

confidence: 65%

Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories

Hassamal

2023

Front. Psychiatry

105

View full text Add to dashboard Cite

show abstract

“…Simvastatin [ 189 – 193 ] and atorvastatin [ 194 ] reduce depressive-like symptoms in animals by decreasing neuroinflammation thanks to the suppression of pro-inflammatory cytokines, P2X7-inflammasome complex, and microglia activation. In addition, the reduction of circulating tumour necrosis factor (TNF)α by simvastatin [ 171 ] and atorvastatin [ 195 ] is likewise associated with improved depressive-like behaviour.…”

Section: Resultsmentioning

confidence: 99%

The pharmacological bases for repurposing statins in depression: a review of mechanistic studies

et al. 2023

View full text Add to dashboard Cite

Statins are commonly prescribed medications widely investigated for their potential actions on the brain and mental health. Pre-clinical and clinical evidence suggests that statins may play a role in the treatment of depressive disorders, but only the latter has been systematically assessed. Thus, the physiopathological mechanisms underlying statins’ putative antidepressant or depressogenic effects have not been established. This review aims to gather available evidence from mechanistic studies to strengthen the pharmacological basis for repurposing statins in depression. We used a broad, well-validated search strategy over three major databases (Pubmed/MEDLINE, Embase, PsychINFO) to retrieve any mechanistic study investigating statins’ effects on depression. The systematic search yielded 8068 records, which were narrowed down to 77 relevant papers. The selected studies (some dealing with more than one bodily system) described several neuropsychopharmacological (44 studies), endocrine-metabolic (17 studies), cardiovascular (6 studies) and immunological (15 studies) mechanisms potentially contributing to the effects of statins on mood. Numerous articles highlighted the beneficial effect of statins on depression, particularly through positive actions on serotonergic neurotransmission, neurogenesis and neuroplasticity, hypothalamic-pituitary axis regulation and modulation of inflammation. The role of other mechanisms, especially the association between statins, lipid metabolism and worsening of depressive symptoms, appears more controversial. Overall, most mechanistic evidence supports an antidepressant activity for statins, likely mediated by a variety of intertwined processes involving several bodily systems. Further research in this area can benefit from measuring relevant biomarkers to inform the selection of patients most likely to respond to statins’ antidepressant effects while also improving our understanding of the physiopathological basis of depression.

show abstract

“…As inflammAtory complex can induce the secretion of pro‐inflammatory cytokines, including IL‐1β and IL‐18, and/or the initiation of pyroptosis, which is a proinflammatory and lytic mode of cell death different from apoptosis. One important function of Ato was regulated downstream to neuroinflammation (Hai‐Na et al, 2020). So, we tested the hippocampal levels of IL‐1β and IL18.…”

Section: Resultsmentioning

confidence: 99%

Atorvastatin ameliorates early brain injury after subarachnoid hemorrhage via inhibition of pyroptosis and neuroinflammation

Chen

Zhang

Yan

et al. 2021

Journal Cellular Physiology

View full text Add to dashboard Cite

Subarachnoid hemorrhage (SAH) is a subtype of stroke with high mortality and morbidity due to the lack of effective therapy. Atorvastatin has been reported to alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH) via reducing reactive oxygen species, antiapoptosis, regulated autophagy, and neuroinflammation. Which was the related to the pyroptosis? Pyroptosis can be defined as a highly specific inflammatory programmed cell death, distinct from classical apoptosis and necrosis. However, the precise role of pyroptosis in atorvastatin‐mediated neuroprotection following SAH has not been confirmed. The present study aimed to investigate the neuroprotection and potential molecular mechanisms of atorvastatin in the SAH‐induced EBI via regulating neural pyroptosis using the filament perforation model of SAH in male C57BL/6 mice, and the hemin‐induced neuron damage model in HT‐22. Atorvastatin or vehicle was administrated 2 h after SAH and hemin‐induced neuron damage. The mortality, neurological score, brain water content, and neuronal death were evaluated. The results show that the atorvastatin treatment markedly increased survival rate, neurological score, greater survival of neurons, downregulated the protein expression of NLRP1, cleaved caspase‐1, interleukin‐1β (IL‐1β), and IL‐18, which indicated that atorvastatin‐inhibited pyroptosis and neuroinflammation, ameliorated neuron death in vivo/vitro subjected to SAH. Taken together, this study demonstrates that atorvastatin improved the neurological outcome in rats and reduced the neuron death by against neural pyroptosis and neuroinflammation.

show abstract

Atorvastatin ameliorates depressive behaviors and neuroinflammatory in streptozotocin-induced diabetic mice

Cited by 18 publications

References 56 publications

Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories

Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories

The pharmacological bases for repurposing statins in depression: a review of mechanistic studies

Atorvastatin ameliorates early brain injury after subarachnoid hemorrhage via inhibition of pyroptosis and neuroinflammation

Contact Info

Product

Resources

About