Effects of the Prenatal Administration of Tetanus Toxoid on the Sociability and Explorative Behaviors of Rat Offspring: A Preliminary Study

Abstract

Objective Autism spectrum disorder (ASD) is a severely disabling psychiatric disease characterized by impairments in communication and social skills. Although efforts have been made to explore the etiology of ASD, its pathophysiology remains unclear. This issue is rendered more challenging by confounding data about the effects of vaccination on disease etiology. In this study, therefore, we investigated the neurodevelopmental effects of maternal tetanus toxoid administration on rat offspring. We hypothesized that the vaccine affects the sociability and preference for social novelty of rat offspring as well as the production of immunological and neurotrophic factors, including tumor necrosis factor-alfa (TNF-α), neuregulin-1 (NRG-1), neuron growth factor (NGF), and oxytocin. Methods The study involved 12 female and 4 male adult Sprague−Dawley rats (238 ± 10 g), which were assigned to two groups. Group 1 (control group) was given 0.5 ml of normal saline (0.9% NaCl) on the 10th day of pregnancy, whereas Group 2 (experimental group) was administered 0.5 ml of tetanus vaccine (tetanus toxoid, 40 IU). Results Maternal tetanus toxoid administration exerted beneficial effects on the sociability and explorative behaviors of the rats. The brain tissue levels of TNF-α, NGF, NRG-1, and oxytocin were higher in the experimental group than those among the controls. All these significant differences were found in both the male and female rats. Conclusion This study is the first to demonstrate the advantages of tetanus toxoid administration in relation to the sociability and explorative behaviors of rat offspring. The results showed that the vaccine also influences NRG-1, neuregulin, and oxytocin production.

Granulocyte colony‐stimulating factor has a sex‐dependent positive effect in the maternal immune activation‐induced autism model

“…The treatment of ASD is unfortunately limited because of the insufficient knowledge about its etiology, and there is no cure for ASD even though it affects a large population. The heterogenic nature of ASD is related to genetic background (Song et al, 2016), neuroanatomical substrates and structures (Komine-Kobayashi et al, 2006), and the phenotypic profile (Sünnetçi et al, 2021). This issue is considered a major challenge for highlighting the etiology, diagnosis and treatment of ASD (Sünnetçi et al, 2021).…”

“…The total number of ambulation (i.e., the number of floor divisions crossed with four paws) was recorded. The floor of the field was then cleaned between each animal with a 70% alcohol‐water solution and dried with paper towel to avoid olfactory cues (Sünnetçi et al, 2021) (Figure 1).…”

“…Generally, there are two factors that determine the behavior in this paradigm: The first is a positive exploratory drive originating from the nature of rodents to explore new environments (for food and shelter), and the second is the animal nature of avoiding open and brightly lit spaces (exposure to predators). The open‐field test is considered useful in determining motor stereotyped behavior, repeated autogrooming, and restriction of research activity in autism model (Sünnetçi et al, 2021).…”

“…The duration of time or latency period for the rat to travel from the lighted to the dark chamber was recorded, but a shock was not delivered. The latency period was recorded up to a maximum of 300 s. The time that the rat took to refrain from crossing into the dark chamber served as an index of the rat's memory (Sünnetçi et al, 2021).…”

Protective Effect of Nimodipine Against Valproic-acid Induced Biochemical and Behavioral Phenotypes of Autism

“…In autistic patients, glutathione levels were higher, reduced glutathione levels were lower, and glutathione redox ratios were diminished. Additionally, animal models show low levels of glutathione (GSH) and interleukin-10 (IL-10) and high levels of thiobarbituric acid reactive (TBAR), IL-6 and tumor necrosis factor (TNF)-α [ 9 , 10 ]. Valproic acid is used to induce autism in rats by exposure during prenatal life 12.5th day.…”