Valproic Acid Promotes Neural Regeneration of Olfactory Epithelium in Adult Mice after Methimazole-Induced Damage

Ogawa, Takao; Takezawa, Kumiko; Shimizu, Shino; Shimizu, Takeshi

doi:10.2500/ajra.2014.28.4027

Cited by 23 publications

(18 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The number of Ki-67 cells was not different between the normal control and the non-TSS post-methimazole mice in our experiment. In past reports that observed the dynamics of Ki-67 during the chronological regeneration in mice olfactory neurons, the number of Ki-67 positive cells was increased on day 7 but returned to normal levels by day 14 (Ogawa 2014, Ueha 2016). However, we did not observe an increase in Ki-67 positive cells at days 14, 28, and 32 in this study.…”

Section: Discussionmentioning

confidence: 85%

Effects of Tokishakuyakusan on Regeneration of Murine Olfactory Neurons In Vivo and In Vitro

et al. 2019

View full text Add to dashboard Cite

Post-upper respiratory tract infection related olfactory dysfunction typically occurs due to neural damage after an upper respiratory tract infection associated with a common cold or influenza. At present, Tokishakuyakusan, a Japanese traditional Kampo medicine, has been found to be effective for post-viral olfactory dysfunction. However, the pharmacodynamics of Tokishakuyakusan in the treatment of post-viral olfactory dysfunction remains unresolved. We investigated the effects of Tokishakuyakusan on the regeneration of olfactory neurons and expression of nerve growth factor (NGF) in neural systems, using in vivo murine studies and in vitro cell culture studies. Eight-week-old BALB/C female mice were fed a pellet diet with or without Tokishakuyakusan. Degeneration of cells in olfactory epithelium was induced by intraperitoneal methimazole injection. Regeneration of olfactory neurons was observed by histological and immunohistochemical procedures. NGF expression in the olfactory bulb was measured by enzyme-linked immunosorbent assay. NGF gene and protein expression were measured using rat primary cultured astrocytes by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. We found that olfactory marker protein, Ki-67, and NGF were more highly expressed in the olfactory epithelium during the regeneration period in mice receiving Tokishakuyakusan. In cultured astrocytes, Tokishakuyakusan as well as its individual components, Atractylodes lancea rhizome and Japanese angelica root, increased NGF expression. Screening assays revealed that NGF production was increased by atractylodin and levistolide A, which are ingredients in Atractylodes lancea rhizome and Japanese angelica root, respectively. These results suggest that Tokishakuyakusan promotes regeneration of olfactory neurons by increasing NGF expression in the olfactory bulb.

show abstract

Section: Discussionmentioning

confidence: 85%

Effects of Tokishakuyakusan on Regeneration of Murine Olfactory Neurons In Vivo and In Vitro

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Since a single injection of MMI-induced hypothyroidism may be transient [29,30], we treated mice with 2 injections of MMI (75 mg/kg, i.p.) once per week in order to cause continuous hypothyroidism, as shown in Figure 1.…”

Section: The Acute Effect Of Sak3 On the Mmi-induced Decrease In Serumentioning

confidence: 99%

Acute Treatment with T-Type Calcium Channel Enhancer SAK3 Reduces Cognitive Impairments Caused by Methimazole-Induced Hypothyroidism Via Activation of Cholinergic Signaling

Noreen¹,

Yabuki²,

Shinoda³

et al. 2018

Pharmacology

View full text Add to dashboard Cite

Hypothyroidism is a common disorder that is associated with psychological disturbances such as dementia, depression, and psychomotor disorders. We recently found that chronic treatment with the T-type calcium channel enhancer SAK3 prevents the cholinergic neurodegeneration induced by a single intraperitoneal (i.p.) injection of methimazole (MMI; 75 mg/kg), thereby improving cognition. Here, we evaluated the acute effect of SAK3 on cognitive impairments and its mechanism of action following the induction of hypothyroidism. Hypothyroidism was induced by 2 injections of MMI (75 mg/kg, i.p.) administered once per week. Four weeks after the final MMI treatment, MMI-treated mice showed reduced serum thyroxine (T4) levels and cognitive impairments without depression-like behaviors. Although acute SAK3 (1.0 mg/kg, p.o.) administration failed to ameliorate the decreased T4 levels and histochemical destruction of the glomerular structure, acute SAK3 (1.0 mg/kg, p.o.) administration significantly reduced cognitive impairments in MMI-treated mice. Importantly, the α7 nicotinic acetylcholine receptor (nAChR)-selective inhibitor methyllycaconitine (MLA; 12 mg/kg, i.p.) and T-type calcium channel-specific blocker NNC 55–0396 (25 mg/kg, i.p.) antagonized the acute effect of SAK3 on memory deficits in MMI-treated mice. We also confirmed that acute SAK3 administration does not rescue reduced olfactory marker protein or choline acetyltransferase immunoreactivity levels in the olfactory bulb or medial septum. Taken together, these results suggest that SAK3 has the ability to improve the cognitive decline caused by hypothyroidism directly through activation of nAChR signaling and T-type calcium channels.

show abstract

“…Compared to the control group, the BMSC transplantation group had increased NGF expression. The expression began to increase 1 week after transplantation and peaked 3-5 weeks after transplantation [15,18,19]. As in our assessment system, measuring the thickness of the epithelium and performing nerve sheath analysis seem reasonable.…”

Section: Discussionmentioning

confidence: 96%

Engraftment and regenerative effects of bone marrow stromal cell transplantation on damaged rat olfactory mucosa

Kwon

Park

et al. 2016

Eur Arch Otorhinolaryngol

View full text Add to dashboard Cite

To develop a new therapeutic method to treat olfactory deficits, we investigated the engraftment and regenerative effects of transplanted bone marrow stromal cells (BMSCs) on damaged rat olfactory mucosa. To induce olfactory nerve degeneration, one side of the olfactory mucosa of Sprague-Dawley rats was damaged via Triton X-100 irrigation. Phosphate-buffered saline containing syngeneic BMSCs was injected into the olfactory mucosa for transplantation. PKH fluorescent cell dye labeling of BMSCs was used to monitor the transplanted cells. After transplantation of BMSCs, the thickness and regeneration of olfactory mucosa were analyzed using hematoxylin-eosin (H&E) staining. S100 immunohistochemical staining was used to measure nerve sheath regeneration. The increase in NGF (nerve growth factor) level in the olfactory mucosa was measured by Western blot analysis. Transplanted bone marrow stromal cells were engrafted to the lamia propria of damaged mucosa. The mean time for normalization of thickness and morphological recovery of the olfactory mucosa was 4 weeks in the therapeutic group and 9 weeks in the control group. S100 immunoreactivity was higher on the BMSC-treated side than on the control side. During regeneration, the expression of NGF increased in the olfactory mucosa of the experimental group. Based on these results, BMSC transplantation accelerated regeneration of olfactory mucosa damaged by Triton X-100, and NGF may be essential to this regenerative process.

show abstract

Valproic Acid Promotes Neural Regeneration of Olfactory Epithelium in Adult Mice after Methimazole-Induced Damage

Cited by 23 publications

References 27 publications

Effects of Tokishakuyakusan on Regeneration of Murine Olfactory Neurons In Vivo and In Vitro

Effects of Tokishakuyakusan on Regeneration of Murine Olfactory Neurons In Vivo and In Vitro

Acute Treatment with T-Type Calcium Channel Enhancer SAK3 Reduces Cognitive Impairments Caused by Methimazole-Induced Hypothyroidism Via Activation of Cholinergic Signaling

Engraftment and regenerative effects of bone marrow stromal cell transplantation on damaged rat olfactory mucosa

Contact Info

Product

Resources

About