Bilateral Olfactory Mucosa Damage Induces the Disappearance of Olfactory Glomerulus and Reduces the Expression of Extrasynaptic α5GABAARs in the Hippocampus in Early Postnatal Sprague Dawley Rats
Chloroform-induced olfactory mucosal degeneration has been reported in adult rats following gavage. We used fixed-point chloroform infusions on different postnatal days (PNDs) to investigate the effects of early olfactory bilateral deprivation on the main olfactory bulbs in Sprague Dawley rats. The experimental groups included rats infused with chloroform (5 μl) or saline (sham, 5 μl) on PNDs 3 and 8, and rats not receiving infusions (control) (n = 6 in all groups). Rats receiving chloroform on PND 3 showed significant hypoevolutism when compared to those in other groups (P < 0.05). There was a complete disappearance and a significant reduction in the size of olfactory glomeruli in the PND 3 and 8 groups, respectively, when compared to the respective sham groups. Rats receiving chloroform on PND 3 had significant memory impairment (P < 0.01) and increased levels of learned helplessness (P < 0.05), as measured using the Morris water maze and tail suspension tests, respectively. GABAA receptor alpha5 subunit (α5GABAAR) expression in hippocampal neurons was significantly lower in rats receiving chloroform on PND 3 than in rats in other groups (P < 0.01), as measured using immunohistochemistry and polymerase chain reaction. There was thus a critical period for the preservation of regenerative ability in olfactory receptor neurons, during which damage and olfactory deprivation led to altered rhinencephalon structure and disappearance of olfactory glomeruli, which induced hypoevolutism. Olfactory deprivation after the critical period had no significant effect on olfactory receptor neuron regeneration, leading to reduced developmental and behavioral effects in Sprague Dawley rats.
KeywordsOlfactory mucosa Olfactory glomerulus α5GABAARs Sprague Dawley Development
We thank the Esa Korpi laboratory members, for their valuable comments on this manuscript. This work is financially supported by Natural Science Foundation China (30960114, 81460644), and West China First-Class Discipline Construction Project in Basic Medicine funded by Ningxia Medical University (NXYLXK2017B07); Thank to the experimental animals’ center of Ningxia Medical University for providing the necessary artificial feeding for suckling rats.
Zheng Xiaomin and Liang Liang together conceived and designed the experiments, then performed most of the experiments.
Hei Changchun, Yang Wenjuan, and Zhang Tingyuan participate in part of the experiments.
Chang Qing, Zheng Xiaomin, and Liang Liang analyzed the data.
Zheng Xiaomin, Liang Liang, Wu Kai, and QinYi contributed the reagents/materials/tools for analysis.
Zheng Xiaomin drafted the paper.
Compliance with Ethical Standards
The authors declare that they have no competing interests.
- Chloroform (PDF), CICAD, 58, World Health Organization (2004)Google Scholar
- Filho CB, Jesse CR, Donato F, Del Fabbro L, de Gomes MG, Goes AT, Souza LC, Giacomeli R, Antunes M, Luchese C, Roman SS, Boeira SP (2016) Neurochemical factors associated with the antidepressant-like effect of flavonoid chrysin in chronically stressed mice. Eur J Pharmacol 791:284–296CrossRefGoogle Scholar
- FU Li-zhi XU, JIN-yi WU, Xiao-ming et al (2007) The advances of the γ-amino butyric acid receptors and relative drugs [J]. China Healthc Innov 02(8):29–35Google Scholar
- Getova DP, Dimitrova DD (2007) Effects of GABAB receptor antagonists CGP63360,CGP76290A and CGP76291A on learning and memory processes in rodents. Cent Eur J Med 2(3):280–293Google Scholar
- Liang L, Xiaomin Z, Chengjun Z et al (2014) Impact of early olfactory deprivation on expression of GABAA receptor δ subunit in dentate gyrus of SD rats [J]. J Ningxia Med Univ. (16):13–18Google Scholar
- Locci A, Porcu P, Talani G, Santoru F, Berretti R, Giunti E, Licheri V, Sanna E, Concas A (2016) Neonatal estradiol exposure to female rats changes GABAA receptor expression and function, and spatial learning during adulthood. Horm Behav 18(87):35–46Google Scholar
- Marcucci F (2011) Axon development and synapse formation in olfactory sensory neurons. Doctor of Philosophy thesis. Columbia UniversityGoogle Scholar
- Moulton DG, Celebi G, Fink RP (1970) Olfaction in mammals—two aspects: proliferation of cells in the olfactory epithelium and sensitivity to odours. In: Wolstenholme GEW, Knight J (eds) Ciba foundation on taste and smell in vertebrates. J. & A. Churchill, London, pp 227–250Google Scholar
- Suzuki Y (2007) Apoptosis and the insulin-like growth factor family in the developing olfactory epithelium. Anat Sci Int 82(4):200–206Google Scholar
- Zheng X, Shen X, Wu K et al (2011) Impact of early olfactory deprivation on the development of SD rat. Chinese J Anat 34(1):8–12Google Scholar
- Zunji K, Zhibin Y (2000) Change of GABAergic neurons in hippocampus of aged learning and memory impaired rats [J]. Prog Anat Sci 6(2):148–151Google Scholar