Lithium therapy subdues neuroinflammation to maintain pyramidal cells arborization and rescues neurobehavioural impairments in ovariectomized rats

Rana, Anil; Sharma, Supriya; Patial, Vikram; Singh, Damanpreet

doi:10.1007/s12035-021-02719-w

Cited by 13 publications

(6 citation statements)

References 81 publications

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“…The present finding of lithium treatment-induced enhancement of whole-brain functional connectivity is consistent with previous studies reporting that lithium can improve the cognitive impairment in patients diagnosed with mild cognitive impairment or dementia ( 34 , 35 ). Implicated mechanisms for these lithium benefits include inhibition of glycogen synthase kinase-3 and reduction of beta-amyloid and hyper-phosphorylated tau ( 34 , 35 ). Our data, from a large-scale imaging perspective, provide evidence suggesting that lithium can improve cognitive impairments by enhancing functional connectivity on a whole-brain level.…”

Section: Discussionsupporting

confidence: 93%

Transcranial direct current stimulation of the occipital lobes with adjunct lithium attenuates the progression of cognitive impairment in patients with first episode schizophrenia

et al. 2022

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BackgroundThere is no standard effective treatment for schizophrenia-associated cognitive impairment. Efforts to use non-invasive brain stimulation for this purpose have been focused mostly on the frontal cortex, with little attention being given to the occipital lobe.Materials and methodsWe compared the effects of nine intervention strategies on cognitive performance in psychometric measures and brain connectivity measured obtained from functional magnetic resonance imaging analyses. The strategies consisted of transcranial direct current stimulation (t-DCS) or repetitive transcranial magnetic stimulation (r-TMS) of the frontal lobe or of the occipital alone or with adjunct lithium, or lithium monotherapy. We measured global functional connectivity density (gFCD) voxel-wise.ResultsAlthough all nine patient groups showed significant improvements in global disability scores (GDSs) following the intervention period (vs. before), the greatest improvement in GDS was observed for the group that received occipital lobe-targeted t-DCS with adjunct lithium therapy. tDCS of the occipital lobe improved gFCD throughout the brain, including in the frontal lobes, whereas stimulation of the frontal lobes had less far-reaching benefits on gFCD in the brain. Adverse secondary effects (ASEs) such as heading, dizziness, and nausea, were commonly experienced by patients treated with t-DCS and r-TMS, with or without lithium, whereas ASEs were rare with lithium alone.ConclusionThe most effective treatment strategy for impacting cognitive impairment and brain communication was t-DCS stimulation of the occipital lobe with adjunct lithium therapy, though patients often experienced headache with dizziness and nausea after treatment sessions.

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Section: Discussionsupporting

confidence: 93%

Transcranial direct current stimulation of the occipital lobes with adjunct lithium attenuates the progression of cognitive impairment in patients with first episode schizophrenia

et al. 2022

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“…In addition to DrD2 signaling, lithium may also affect cyclic AMP driven signaling downstream of the D1 dopamine receptor (DrD1). Indeed, the transcription factor cAMP response element-binding protein (CREB) is a major target on which both DrD1 and GSK3 signaling can converge ( Wang et al, 1994 ; Beaulieu and Gainetdinov, 2011 ; Rana et al, 2022 ). To our knowledge, the possibility of an interaction between DrD1 and GSK3 modulation of CREB activity has not been directly tested in the context of a contribution to the full scope of lithium effects in rodents.…”

Section: Biological Functions Modulated By Gsk3 and Lithiummentioning

confidence: 99%

“…Analysis of protein interaction networks indicate that CREB can interact with several proteins encoded by GWAS-identified psychiatric disorder risk genes ( Xiao et al, 2018 ). Furthermore, chronic lithium treatment increases CREB Ser133 phosphorylation and BDNF levels, preventing cognitive impairments and unregulated stress response ( Grimes and Jope, 2001 ; Kopnisky et al, 2003 ; Miller et al, 2007 ; Fan et al, 2015 ; Rana et al, 2022 ).…”

Section: Direct Substrates Of Gsk3 Regulated By Lithiummentioning

confidence: 99%

“…Paradoxically, studies of chronic lithium treatment impact on CREB found decreased pSer133 CREB, as well as increased GluA1 internalization and decreased memory consolidation ( Chen et al, 1999 ; Tardito et al, 2007 ; Mavrikaki et al, 2014 ; Amiri et al, 2020 ). However, lithium can also increase CREB activity (by increasing pSer133; Grimes and Jope, 2001 ; Kopnisky et al, 2003 ; Miller et al, 2007 ; Fan et al, 2015 ; Rana et al, 2022 ). This suggests that lithium has both inhibitory and disinhibitory effects on CREB in different neuronal populations or experimental systems.…”

Section: Direct Substrates Of Gsk3 Regulated By Lithiummentioning

confidence: 99%

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Inhibition of glycogen synthase kinase 3 by lithium, a mechanism in search of specificity

Chatterjee

Beaulieu

2022

Front. Mol. Neurosci.

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Inhibition of Glycogen synthase kinase 3 (GSK3) is a popular explanation for the effects of lithium ions on mood regulation in bipolar disorder and other mental illnesses, including major depression, cyclothymia, and schizophrenia. Contribution of GSK3 is supported by evidence obtained from animal and patient derived model systems. However, the two GSK3 enzymes, GSK3α and GSK3β, have more than 100 validated substrates. They are thus central hubs for major biological functions, such as dopamine-glutamate neurotransmission, synaptic plasticity (Hebbian and homeostatic), inflammation, circadian regulation, protein synthesis, metabolism, inflammation, and mitochondrial functions. The intricate contributions of GSK3 to several biological processes make it difficult to identify specific mechanisms of mood stabilization for therapeutic development. Identification of GSK3 substrates involved in lithium therapeutic action is thus critical. We provide an overview of GSK3 biological functions and substrates for which there is evidence for a contribution to lithium effects. A particular focus is given to four of these: the transcription factor cAMP response element-binding protein (CREB), the RNA-binding protein FXR1, kinesin subunits, and the cytoskeletal regulator CRMP2. An overview of how co-regulation of these substrates may result in shared outcomes is also presented. Better understanding of how inhibition of GSK3 contributes to the therapeutic effects of lithium should allow for identification of more specific targets for future drug development. It may also provide a framework for the understanding of how lithium effects overlap with those of other drugs such as ketamine and antipsychotics, which also inhibit brain GSK3.

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“…Moreover, findings from a Chinese woman-based cohort study showed that symptoms of anxiety and depression are more common during and after menopause than in premenopausal women ( Tang et al, 2019 ). Therefore, the ovariectomized (OVX) mice model was used to mimic clinical postmenopausal condition ( Rana et al, 2022 ). Researchers have found that after gavage administration of berberine (100 mg/kg), the increased content of equol (a chemical structure similar to the hormone estrogen that binds to estrogen receptors) in the OVX rat model transplanted with fecal microbiota, enriched the taxa involved in isoflavone biotransformation and significantly reduced anxiety-like behavior.…”

Section: Introductionmentioning

confidence: 99%

Current Evidence and Future Directions of Berberine Intervention in Depression

Zhu

Sun

et al. 2022

Front. Pharmacol.

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A major type of serious mood disorder, depression is currently a widespread and easily overlooked psychological illness. With the low side effects of natural products in the treatment of diseases becoming the pursuit of new antidepressants, natural Chinese medicine products have been paid more and more attention for their unique efficacy in improving depression. In a view from the current study, the positive antidepressant effects of berberine are encouraging. There is a lot of work that needs to be done to accurately elucidate the efficacy and mechanism of berberine in depression. In this review, the relevant literature reports on the treatment of depression and anxiety by berberine are updated, and the potential pharmacological mechanism of berberine in relieving depression has also been discussed.

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Lithium therapy subdues neuroinflammation to maintain pyramidal cells arborization and rescues neurobehavioural impairments in ovariectomized rats

Cited by 13 publications

References 81 publications

Transcranial direct current stimulation of the occipital lobes with adjunct lithium attenuates the progression of cognitive impairment in patients with first episode schizophrenia

Transcranial direct current stimulation of the occipital lobes with adjunct lithium attenuates the progression of cognitive impairment in patients with first episode schizophrenia

Inhibition of glycogen synthase kinase 3 by lithium, a mechanism in search of specificity

Current Evidence and Future Directions of Berberine Intervention in Depression

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