Reduced Nasal Transport of Insulin-Like Growth Factor-1 to the Mouse Cerebrum With Olfactory Bulb Resection

Kondo

et al. 2018

Front. Aging Neurosci.

Background: Olfaction is known to be impaired by aging. We hypothesized that insulin-like growth factor-1 (IGF-1) administered at an appropriate dose could prevent age-induced negative effects on olfactory receptor neurons (ORNs). We explored the effects of low- and high-dose administration of IGF-1 on the ORN cell system in aged mice and investigated the involvement of the cellular mechanisms of IGF-1 in the regeneration of ORNs in aged mice.Methods: We subcutaneously administered recombinant human IGF-1 (rhIGF-1) to 16-month-old male mice over 56 days, and then examined the histological effects of rhGF-1 on cellular composition, cell proliferation, and cell death in the aged olfactory epithelium (OE), by comparing among saline-treated and low- and high-dose rhIGF-1-treated mice.Results: Low-dose rhIGF-1 administration increased the numbers of olfactory progenitors, immature ORNs, and mature ORNs in the OE, despite an increase in Cas3+ apoptotic cells. Notably, high-dose rhIGF-1 administration increased the numbers of only immature ORNs, not olfactory progenitors and mature ORNs, with a concurrent increase in apoptotic cells.Conclusion: Our data suggest that in aged mice, IGF-1 administered at an appropriate dose could increase the number of mature ORNs and further human studies may contribute to the development of treatments for aging-related olfactory impairment.

Section: Discussionmentioning

confidence: 99%

Dose-Dependent Effects of Insulin-Like Growth Factor 1 in the Aged Olfactory Epithelium

Kondo

et al. 2018

Front. Aging Neurosci.

“…Therefore, olfactory neurons are easily damaged by viruses or mechanical injury. On the other hand, olfactory neurons provide a useful drug delivery route into the central nervous system (Shiga et al 2014).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

Self 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.

“…None of the subjects examined here experienced major side effects following the nasal administration of 201 Tl, perhaps due to the small dose of administered 201 Tl. The absorbed doses of 201 Tl were estimated as 0.59 mGy in the lens and 0.067 mGy in the brain after the nasal administration of 22 MBq 201 Tl by applying the MIRD formula 7, 15 . Thus far, no serious side effects have been reported in subjects after olfacto-scintigraphy.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of olfactory nerve damage measured with thallium-based olfactory imaging in patients with idiopathic olfactory dysfunction

Shiga

Taki

Okuda

et al. 2017

Sci Rep

Self Cite

Idiopathic olfactory disorder is resistant to treatment, and the recovery time is long. This study investigated the prognostic value of the migration of nasally administered thallium-201 to the olfactory bulb (thallium migration to the OB), a measure of olfactory nerve damage, in patients with idiopathic olfactory disorders. Twenty-four patients with idiopathic olfactory disorders were enrolled in the study (7 women and 17 men; aged 23–73 years). We retrospectively analyzed potential prognostic markers in subjects who underwent thallium-based olfactory imaging with the nasal administration of thallium-201 before conventional treatment with the Japanese herbal medicine tokishakuyakusan and compared those data with the prognosis. Log-rank tests were performed to assess the relationship between thallium migration to the OB (<4.6% [low] vs. ≥4.6% [high]; data dichotomized at the optimal cutoff value) and the duration until recovery of the odor recognition threshold determined by a standard olfactory function test (T&T olfactometry) after the treatment. Upon statistical analysis, we found that high thallium migration to the OB was significantly correlated with better prognosis in patients. Our results suggest that patients with intact olfactory nerve fibers could be selected using thallium-based imaging for the long-term follow-up of olfactory dysfunction.