Abstract
BackgroundRodent models may guide investigations towards identifying either environmental neuro-toxicants or drugs with neuro-therapeutic effects. This work aims to study the therapeutic effects of bee pollen on brain glutamate excitotoxicity and the impaired glutamine-glutamate- gamma amino butyric acid (GABA) circuit induced by propionic acid (PPA), a short chain fatty acid, in rat pups.MethodsTwenty-four young male Western Albino rats 3–4 weeks of age, and 45–60 g body weight were enrolled in the present study. They were grouped into four equal groups: Group 1, the control received phosphate buffered saline at the same time of PPA adminstration; Group 2, received 750 mg/kg body weight divided into 3 equal daily doses and served as acute neurotoxic dose of PPA; Group 3, received 750 mg/kg body weight divided in 10 equal doses of 75 mg/kg body weight/day, and served as the sub-acute group; and Group 4, the therapeutic group, was treated with bee pollen (50 mg/kg body weight) for 30 days after acute PPA intoxication. GABA, glutamate and glutamine were measured in the brain homogenates of the four groups.ResultsThe results showed that PPA caused multiple signs of excitotoxicity, as measured by the elevation of glutamate and the glutamate/glutamine ratio and the decrease of GABA, glutamine and the GABA/glutamate ratio. Bee pollen was effective in counteracting the neurotoxic effects of PPA to a certain extent.ConclusionIn conclusion, bee pollen demonstrates ameliorating effects on glutamate excitotoxicity and the impaired glutamine-glutamate-GABA circuit as two etiological mechanisms in PPA-induced neurotoxicity.
Highlights
Rodent models may guide investigations towards identifying either environmental neuro-toxicants or drugs with neuro-therapeutic effects
The second and third groups were orally administered a neurotoxic dose of propionic acid (PPA) (750 mg/ kg body weight divided in 3 doses of 250 mg/kg body weight/day served as the acute group [8], and 750 mg/kg body weight divided in 10 equal doses of 75 mg/kg body weight/day served as the sub-acute group)
Compared to the control groups, the PPA-treated rats exhibited a significant increase in Glu and the Glu/Gln ratio with a concomitant decrease of gamma amino butyric acid (GABA), Gln, and the GABA/Glu ratio
Summary
Rodent models may guide investigations towards identifying either environmental neuro-toxicants or drugs with neuro-therapeutic effects. This work aims to study the therapeutic effects of bee pollen on brain glutamate excitotoxicity and the impaired glutamine-glutamate- gamma amino butyric acid (GABA) circuit induced by propionic acid (PPA), a short chain fatty acid, in rat pups. Glutamate receptors are mainly localized in brain areas that have been repeatedly implicated in autism, such as the cerebellum and hippocampus [1] Excitatory glutamate signaling through glutamate receptors (GluRs) plays a key role in cortical development [2] which indicate its involvement in the etiology of autistic features. Glutamate (Glu) is an amino acid that functions as an Glutamate is usually synthesized in the neuron and is transported into glial cells from the synaptic cleft, it is converted into Gln by the enzyme glutamine synthetase (GS), which is completely absent in neuronal cells [3]. Glutamine is transported back into the neuron, where it is deaminated by glutaminase, once again forming Glu [3].
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