Elsevier

Archives of Oral Biology

Volume 110, February 2020, 104596
Archives of Oral Biology

The prospective role of mesenchymal stem cells exosomes on circumvallate taste buds in induced Alzheimer’s disease of ovariectomized albino rats: (Light and transmission electron microscopic study)

https://doi.org/10.1016/j.archoralbio.2019.104596Get rights and content

Highlights

  • Alzheimer’s disease has degenerative effects on circumvallate taste buds.

  • Alzheimer’s disease has degenerative effects on the gustatory nerve fibers.

  • BM-MSC-derived exosomes have the ability to improve the destructive changes.

Abstract

Objective

To elucidate the effect of Alzheimer’s disease on the structure of circumvallate papilla taste buds and the possible role of exosomes on the taste buds in Alzheimer’s disease.

Design

Forty two ovariectomized female adult albino rats were utilized and divided into: Group I: received vehicle. Group II: received aluminum chloride to induce Alzheimer’s disease. Group III: after the induction of Alzheimer’s disease, each rat received single dose of exosomes then left for 4 weeks. The circumvallate papillae were prepared for examination by light and transmission electron microscope. Statistical analysis: histomorphometric data were statistically analyzed.

Results

Histological examination of circumvallate papilla in Group I showed normal histological features. Group II revealed distorted features. Group III illustrated nearly normal histological features of circumvallate. Silver impregnation results showed apparently great number of heavily impregnated glossopharyngeal nerve fibers in both Groups I & III but markedly decreased in Group II. Synaptophysin-immunoreactivity was strong in Group I, mild in Group II and moderate in Group III. The ultra-structural examination of taste bud cells revealed normal features in Group I, distorted features in Group II and almost normal features in Group III. Statistically highest mean of Synaptophysin-immunoreactivity area% was for Group I, followed by Group III, and the least value was for Group II.

Conclusions

Alzheimer’s disease has degenerative effects. Bone marrow mesenchymal stem cell (BM-MSC)-derived exosomes have the ability to improve the destructive changes induced by Alzheimer’s disease.

Introduction

Taste buds are intra-epithelial structures scattered on the dorsal surface of the mammalian tongue (fungiform, circumvallate, and foliate papillae), in addition to the oral side of the soft palate, and oropharyngeal areas (Chandrashekar, Hoon, Ryba, & Zuker, 2006; Kobayashi et al., 2005). The taste buds are controlled by the cranial nerves (VII, IX, X, XI) via the thalamus (Suto et al., 2014).

Mammalian taste buds consist of different populations of mature, elongated cells that are classified into three main types; (type I, II and III), beside basal cells (type IV). The elongated cell possesses a bipolar shape that fill the entire epithelium thickness. It has an apical process that extends into an opening in the epithelium surface (taste pore) and has also a basal process that reaches the basal lamina (Chaudhari & Roper, 2010; Finger, 2005).

Each type of cells has an exclusive function. Type I cells are supporting cells that surround other elongated cells (Bartel, Sullivan, Lavoie, Sevigny, & Finger, 2006; Zimmermann, Zebisch, & Strater, 2012). Type II (receptor) cells are responsible for sweet, bitter and umami tastes. They express metabotropic taste receptor proteins coupled with G-protein (G-protein-coupled receptors) which are required to perform their transduction function (Chandrashekar et al., 2006; Clapp, Yang, Stoick, Kinnamon, & Kinnamon, 2004). Type III (synaptic) cells express the channels responsible for the transduction of different taste sensations mainly sour and possibly salty taste (Huang, Maruyama, Stimac, & Roper, 2008; Kataoka et al., 2008). Type IV (basal) cells are proliferative cells that can differentiate into the previously mentioned types of mature cells. The basal cells appear as round or ovoid shaped cells resting on the base of the taste buds (Chaudhari & Roper, 2010; Finger, 2005).

Disturbance in taste sensation “related to aging, diseases or drugs side effects” defiantly affects the life’s quality as aberrations in taste homeostasis influence food intake which leads to anorexia, malnutrition and therefore weight loss (Cohn, Kim, Huang, Brand, & Wang, 2010; Shin et al., 2012).

Failure to recognize different tastes warns of clinical symptoms of several neurodegenerative and neuropsychiatric diseases that require immediate intervention (Huttenbrink, Hummel, Berg, Gasser, & Hahner, 2013; Stamps, Bartoshuk, & Heilman, 2013).

Alzheimer’s disease is one of age-related diseases. It is considered as a common chronic progressive neurodegenerative disorder that leads to deficiency of perception-related functions due to selective loss of neurons in the central nervous system (Anand, Gill, & Mahdi, 2014; Bossy-Wetzel, Schwarzenbacher, & Lipton, 2004). Moreover, it was reported that Alzheimer’s disease is one of neurological diseases that are associated with taste dysfunction and disturbance of different taste perception (sweet, salt, bitter and sour) (Epstein, Smutzer, & Doty, 2016).

95% of Alzheimer’s disease suffering people are aged 65 or older (late-onset, or sporadic), while the remaining 5% are developed before age 65 due to genetic mutations (early onset, non-sporadic, or familial), (Holtzman, Morris, & Goate, 2011). It was found that constant exposure to aluminum leads to pathogenesis of Alzheimer’s disease (Zaky, Mohammad, Moftah, Kandeel, & Bassiouny, 2013).

Patients with mild to moderate degree of Alzheimer’s disease depend on drugs that treat only the symptoms or assist in maintaining the symptoms from getting worse for a restricted time (Beheshti & Aghaie, 2016). However, the used drugs are linked with many side effects such as bradycardia, agitation, confusion, dyspepsia, increased sweating, and tremors (Birks & Flicker, 2006).

Recently it was proved that, the exosomes derived from mesenchymal stem cells have the ability to regenerate the functions of many tissues through their paracrine effect by secretion of growth factors, cytokines, or chemokines (Nakamura et al., 2015; Sabin & Kikyo, 2014).

Exosomes are released by almost all eukaryotic cells (Kosaka et al., 2010; Yanez-Mo, Siljander, & Andreu, 2015). The expression “exosomes” refers to intraluminal vesicles of multivesicular bodies produced by reverse budding of endosomal membrane. Intraluminal vesicles are secreted upon fusion of multivesicular bodies with the plasma membrane (van Niel, D’Angelo, & Raposo, 2018).

The exosomes exerted their functions through fusion with the target cell and release of active small molecules like messenger-RNA, micro-RNA, lipids and proteins from their cell of origin into the membranes and cytosol of the target cell. This consequently stimulates the surface receptors and thus regulates the target cell (Valadi et al., 2007; Yanez-Mo et al., 2015).

From the preceding facts, this study was conducted in an attempt to explain the histological changes in circumvallate taste buds that occurs in Alzheimer’s disease and the potential effect of exosomes obtained from bone marrow mesenchymal stem cells (BM-MSCs) on such changes.

Section snippets

Isolation and culture of BM-MSCs

BM-MSCs were obtained from four male albino rats 10 weeks old at the Biochemistry and Microbiology Unit, Faculty of Medicine, Cairo University.

Bone marrow was flushed out from tibias of the rats using phosphate buffered saline (GIBCO™/Invitrogen, Grand Island, New York, USA) then centrifuged at 1000 rpm for 5 min. The upper layer was discarded leaving mononuclear cell layer which was washed in phosphate buffered saline twice then centrifuged at 200 × g for 10 min at 10 °C. The isolated BM-MSCs

Group I (Control)

Histological examination of Group I showed the characteristic inverted cone shape of circumvallate papilla. It was marked out by a deep furrow or trench. The papilla was covered by apparently thin stratified squamous epithelium with noticeable regular thin keratin layer. On its lateral surface, the epithelium lining the furrow contained obviously numerous taste buds. The papilla consisted of a central core of connective tissue “the lamina propria” with numerous secondary papillae projecting

Discussion

Alzheimer’s disease is neurodegenerative disorder characterized by microglia-triggered inflammation, over activation of glutamate receptors, increased intracellular calcium levels, production of nitric oxide species, release of free radicals, mitochondrial dysfunction and synaptic dysfunction (Bossy-Wetzel et al., 2004). Development of dysgeusia is mediated by activation of inflammatory pathways that disturbs the homeostasis of the taste buds (Wang, Zhou, Brand, & Huang, 2009). MSC-derived

Conclusions

Alzheimer’s disease has degenerative effects on circumvallate taste buds and the gustatory nerve fibers. BM-MSC-derived exosomes have the ability to improve the destructive changes in the taste buds and their innervations induced by Alzheimer’s disease.

Ethical Approval

This research follows the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications No. 8023, revised 1978)

Financial support

This research did not receive any specific grant from funding agencies.

Declaration of Competing Interest

None declared.

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