Involvement of Intestinal Goblet Cells and Changes in Sodium Glucose Transporters Expression: Possible Therapeutic Targets in Autistic BTBR T+Itpr3tf/J Mice

Abstract

Autism spectrum disorder is a neurodevelopmental syndrome with a complicated etiology and could be responsible for disrupted gastrointestinal tract microbiota. The aim of this work was to study intestinal samples from an autistic animal model (BTBR mouse strain) to better describe gastrointestinal alterations. We performed a morphological and biological evaluation of small intestine samples. In terms of morphology, we studied the goblet cells, cells of intestinal mucosal responsible for the production and maintenance of the protective mucous blanket. Alterations in their secretion may indicate an altered rate of mucus synthesis and this is one of the possible causes of gastrointestinal problems. In terms of biological evaluation, impaired regulation of glucose homeostasis regulated by sodium-glucose transporters has been suggested as an important component of obesity and associated comorbidities; therefore, this study analyzed the expression of sodium/glucose transporter-1 and -3 in BTBR mice to better define their role. We demonstrated that, in BTBR mice as compared to C57BL/6J (B6) strain animals: (1) The goblet cells had different protein content in their vesicles and apparently a larger number of Golgi cisternae; (2) the expression and level of sodium/glucose transporters were higher. These findings could suggest new possible targets in autism spectrum disorder to maintain mucus barrier function.

Impairment in the Intestinal Morphology and in the Immunopositivity of Toll-like Receptor-4 and Other Proteins in an Autistic Mouse Model

“…During the experimental study, all forty BTBR and CTR mice remained healthy, readily consuming their daily food, but they gained weight as previously described by our group [ 3 , 15 ] and now reported in Table 1 .…”

“…Our research group has already analyzed in a previous paper the role of the goblet cells in maintaining the intestinal functionality, focusing also on the alterations that could involve these cells in patients affected by the ASD-related dysbiosis [ 15 ]. Based on these findings, we performed this study to examine the morphology of the small intestine in BTBR mice but, moreover, to deepen the first results obtained, expanding our analysis, and considering not specific cells, but the more general condition of chronic inflammation to which autistic patients seem to be constantly subjected.…”

“…Each mouse at the age of 13 weeks was deeply anesthetized (isoflurane 5%) and transcardically perfused with saline followed by 1 L of 4% paraformaldehyde in phosphate buffer saline (0.1 M, pH 7.4). For morphological, immunohistochemical and ultrastructural evaluation, the gut was carefully removed from each mouse [ 3 , 15 ].…”

“…The etiology of ASD remains unclear, although there are suggestions of an association between ASD and inflammatory mucosal pathology, and, recently, a link also been suggested between gastrointestinal (GI) problems and symptoms in autistic patients [ 10 ]. Moreover, many studies have also shown that most autistic children have GI disorders such as chronic diarrhea, abdominal pain, vomiting, gastroesophageal reflux and altered intestinal integrity [ 11 , 12 , 13 , 14 , 15 ]. Last but not least, many researchers recently have focused their attention on the role that the enteric nervous system (ENS) could have in determining GI symptoms [ 16 ].…”

“…These mice show low reciprocal social interactions, repetitive behaviors such as cognitive inflexibility, increased grooming, impaired juvenile play and poor social approach [ 20 , 21 , 34 ]. Previously, our team [ 15 ] and other groups [ 42 ] have demonstrated that these mice have alterations in intestinal mucosal cells and a different presence of the sodium/glucose transporters. These results suggest a probability of becoming overweight or even obese, conditions that are comorbidities in autistic patients.…”