Prenatal zinc prevents communication impairments and BDNF disturbance in a rat model of autism induced by prenatal lipopolysaccharide exposure

Abstract

Aims: Previous investigations by our group have shown that prenatal exposure to lipopolysaccharide (LPS),which mimics infections by Gram-negative bacteria, induced autistic-like behavior. No effective treatment yet exists for autism. Therefore, we used our rat model to test a possible treatment for autism.We selected zinc as the prenatal treatment to prevent or ease the impairments induced by LPS because LPS induces hypozincaemia.Materials and methods:We evaluated the effects of LPS and zinc on female reproductive performance. Communication,which is impaired in autism,was tested in pups by ultrasonic vocalizations. Plasma levels of brain-derived neurotrophic factor (BDNF) were determined because it has been considered an autism important biomarker.Key findings: Prenatal LPS exposure reduced offspring number and treatment with zinc prevented this reduction.Moreover, pups that were prenatally exposed to LPS spent longer periods without calling their mothers, and posttreatment with zinc prevented this impairment induced by LPS to the same levels as controls. Prenatal LPS also increased BDNF levels in adult offspring, and posttreatment with zinc reduced the elevation of BDNF to the same levels as controls.Significance: BDNF hyperactivity was also found in several studies of autistic patients. Together with our previous studies, our model of prenatal LPS induced autistic-like behavioral, brain, and immune disturbances. This suggests that it is a valid rat model of autism. Prenatal zinc prevented reproductive, communication, and BDNF impairments.The present study revealed a potential beneficial effect of prenatal zinc administration for the prevention of autism with regard to the BDNF pathway.

Autism phenotypes in ZnT3 null mice: Involvement of zinc dyshomeostasis, MMP-9 activation and BDNF upregulation

“…Because the brain contains a dynamic pool of labile zinc, which is stored in synaptic vesicles through the action of ZnT3 (SLC30A3) and released upon depolarization to modulate synaptic physiology, it has been proposed that abnormalities in synaptic zinc levels may contribute to the above-mentioned brain dysfunctions such as microcephaly that are observed in nutritionally zinc-deficient animals33. Consistent with these ideas, dietary supplementation or injections of zinc have been shown to have beneficial effects in ASD patients34353637.…”

Astaxanthin ameliorates prenatal LPS-exposed behavioral deficits and oxidative stress in adult offspring

“…The AST treatment was given for 6 weeks; from postnatal day 91 to 132 with the intent to reduce the stress level that was enhanced by prenatal LPS exposure in our mice model. This timing of AST treatment was rationally decided after reviewing the previous studies demonstrating neurochemical abnormalities in the adults after prenatal LPS administration [ 72 – 74 ]. In control_AST group, only astaxanthin was given to the animals that were not prenatally LPS-exposed for better comparison and to understand the effect of AST on prenatally LPS-exposed mice.…”

Immunity and ultrasonic vocalization in rodents

“…Another study reported that no differences in the number and total vocalization, and mean and maximum call duration were detected in the 11‐day‐old offspring of Wistar rats that received LPS (100 μg/kg) on gestational day 9.5, when they were tested for 40‐kHz USVs in the maternal‐isolation paradigm . The results discussed above are summarized in Table .…”