Valproic acid‐mediated Hsp70 induction and anti‐apoptotic neuroprotection in SH‐SY5Y cells

Pan, Tianhong; Li, Xinqun; Xie, Wenjie; Jankovic, Joseph

doi:10.1016/j.febslet.2005.10.067

Cited by 70 publications

(43 citation statements)

References 30 publications

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“…Therefore, their anti-apoptotic effects on neural precursor cell might be involved in a part of common mood stabilizing effects. Results of some studies have suggested that internal pathway-related factors (e.g., GSK-3β, Bcl-2, HSP70) might be candidates of the common anti-apoptotic effects of mood stabilizers Li et al, 2002;Jope and Bijur, 2002;Ren et al, 2003;Pan et al, 2005). Furthermore, Williams et al showed that prolyl oligopeptidase is a candidate factor of the common effects of mood stabilizers on the collapse of sensory neuron growth cones (Williams et al, 2002); prolyl oligopeptidase is reportedly involved in apoptosis (Okada et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Effects of mood stabilizers on adult dentate gyrus-derived neural precursor cells

Boku¹,

Nakagawa²,

Masuda³

et al. 2011

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Neurogenesis in the adult dentate gyrus (DG) is considered to be partly involved in the action of mood stabilizers. However, it remains unclear how mood stabilizers affect neural precursor cells in adult DG. We have established a culture system of adult rat DG-derived neural precursor cells (ADP) and have shown that lithium, a mood stabilizer, and dexamethasone, an agonist of glucocorticoid receptor, reciprocally regulate ADP proliferation. Neurogenesis constitutes not only proliferation of neural precursor cells but also apoptosis and differentiation. To develop further understanding of mood stabilizer effects on neural precursor cells in adult DG, we investigated and compared the effects of four common mood stabilizers--lithium, valproate, carbamazepine, and lamotrigine--on ADP proliferation, apoptosis, and differentiation. ADP proliferation, decreased by dexamethasone, was examined using Alamar Blue assay. Using TUNEL assay, ADP apoptosis induced by staurosporine was examined. The differentiated ADP induced by retinoic acid was characterized by immunostaining with anti-GFAP or anti-Tuj1 antibody. Lithium and valproate, but not carbamazepine and lamotrigine, recovered ADP proliferation decreased by dexamethasone. All four mood stabilizers decreased ADP apoptosis.Retinoic acid differentiated ADP into both neurons and astrocytes. Lithium and carbamazepine increased the ratio of neurons and decreased that of astrocytes. However, valproate and lamotrigine increased the ratio of astrocytes and decreased that of neurons. Therefore, these four stabilizers exhibited both common and differential effects on ADP proliferation, apoptosis, and differentiation.

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Section: Discussionmentioning

confidence: 99%

Effects of mood stabilizers on adult dentate gyrus-derived neural precursor cells

Boku¹,

Nakagawa²,

Masuda³

et al. 2011

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…Neurons treated with VPA likewise survive for longer periods of time in vitro than untreated controls. 13 To test whether VPA promoted survival by inhibiting apoptosis, a TUNEL assay was performed after 6 days of VPA treatment. VPA-treated cultures had fivefold fewer apoptotic nuclei, indicating VPA promoted myotube survival.…”

Section: Discussionmentioning

confidence: 99%

“…It activates Akt in neurons and promotes their survival. 13 VPA is also known to have histone deacetylase inhibitor activity. 14 We report here the isolation and use of myogenic cells to identify VPA as a molecule that enhances ␣7 integrin expression.…”

mentioning

confidence: 99%

Valproic Acid Activates the PI3K/Akt/mTOR Pathway in Muscle and Ameliorates Pathology in a Mouse Model of Duchenne Muscular Dystrophy

Gurpur

Liu

Burkin

et al. 2009

The American Journal of Pathology

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Duchenne muscular dystrophy is a lethal neuromuscular disease that currently has no effective therapy. Transgenic overexpression of the ␣7 integrin in mdx/ utrn ؊/؊ mice, a model of Duchenne muscular dystrophy ameliorates the disease. We have isolated and used ␣7 ؉/؊ muscle cells expressing ␤-galactosidase, driven by the endogenous ␣7 promoter, to identify compounds that increase ␣7 integrin levels. Valproic acid (VPA) was found to enhance ␣7 integrin levels, induce muscle hypertrophy, and inhibit apoptosis in myotubes by activating the Akt/mTOR/p70S6K pathway. This activation of the Akt pathway occurs within 1 hour of treatment and is mediated by phosphatidylinositol 3-OH kinase. To evaluate the potential use of VPA to treat muscular dystrophy, mdx/utrn ؊/؊ mice were injected with the drug. Treatment with VPA lowered collagen content and fibrosis, and decreased hind limb contractures. VPA-treated mice also had increased sarcolemmal integrity and decreased damage , decreased CD8-positive inflammatory cells , and higher levels of activated Akt in their muscles. Thus , VPA has important biological effects that may be applicable for the treatment of muscular dystrophy.

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“…Findings from an experiment of SH-SY5Y cells challenged with the mitochondrial complex I inhibitor rotenone suggest that VPA's neuroprotective effects may also involve HSP70 and may be associated with reductions in the release of cytochrome c and the cleavage of caspase-3 and -9 (Pan et al, 2005). In rat cortical neuronal cultures, HSP70 participated in VPA neuroprotection against short-term glutamate excitotoxicity.…”

Section: A Neurotrophic and Angiogenic Factors Modulated By Lithium mentioning

confidence: 99%

Therapeutic Potential of Mood Stabilizers Lithium and Valproic Acid: Beyond Bipolar Disorder

et al. 2013

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Valproic acid‐mediated Hsp70 induction and anti‐apoptotic neuroprotection in SH‐SY5Y cells

Cited by 70 publications

References 30 publications

Effects of mood stabilizers on adult dentate gyrus-derived neural precursor cells

Effects of mood stabilizers on adult dentate gyrus-derived neural precursor cells

Valproic Acid Activates the PI3K/Akt/mTOR Pathway in Muscle and Ameliorates Pathology in a Mouse Model of Duchenne Muscular Dystrophy

Therapeutic Potential of Mood Stabilizers Lithium and Valproic Acid: Beyond Bipolar Disorder

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