The effects of repeated antibiotic administration to juvenile BALB/c mice on the microbiota status and animal behavior at the adult age

Ceylani, Taha
Jakubowska-Dogru, Ewa
Gurbanov, Rafig
Teker, Hikmet Taner
Gözen, Ayşe Gül
Recent studies carried on germ -free (GF) animal models suggest that the gut microbiota (GM) may play a role in the regulation of anxiety, mood, and cognitive abilities such as memory and learning processes. Consistently, any treatment disturbing the gut microbiota, including the overuse of antibiotics, may influence the brain functions and impact behavior. In the present study, to address this issue, two wide-spectrum antibiotics (ampicillin and cefoperazone, 1 g/l) were repeatedly applied throughout a 6-week period to initially 21-day-old male BALB/c mice. Antibiotics were administered separately or in a mixed fashion. On the completion of the antibiotic treatment, all mice were subjected to the behavioral tests. The serum levels of corticosterone and brain-derived neurotropic factor (BDNF) were assessed. Gut microbiota profiles were obtained by using denaturing gradient gel electrophoresis system, DGGE, from fecal samples. Ampicillin had a greater impact on both, gut microbiota composition and mice behavior compared to cefoperazone. All antibiotic-treated groups manifested a decrease in the locomotor activity and reduced recognition memory. However, the ampicillin-treated groups showed a higher anxiety level as assessed by the open field and the elevated plus maze tests and an increased immobility (behavioral despair) in the forced swim test. Obtained results evidently show that in mice, a repeated antibiotic treatment applied during adolescence, parallel to the changes in GM, affects locomotor activity, affective behavior and cognitive skills in young adults with ampicillin specifically enhancing anxiety-and depressive-like responses. Lower levels of serum BDNF were not associated with cognitive impairment but with changes in affective-like behaviors. Repeated administration of neither ampicillin nor cefoperazone affected basal serum corticosterone levels. This is one of the few studies demonstrating changes in a behavioral phenotype of young-adult subjects who were previously exposed to a repeated antibiotic treatment.


Hippocampal levels of ChAT, PKA, phospho-PKA and phospho-CaMKII alpha but not CaMKII alpha positively correlate with spatial learning skills in rats
Gokcek-Sarac, Cigdem; Adalı, Orhan; Jakubowska-Dogru, Ewa (Elsevier BV, 2013-06-17)
Despite very extensive investigations on molecular processes underlying memory formation, there are very few studies examining potential differences in the brain biochemistry between "good" and "poor" learners belonging to a random population of young animals. In the present study, an attempt was made to correlate individual variation in spatial learning in young-adult Long-Evans rats with hippocampal levels of protein kinase A (PKA), calcium/calmodulin-dependent protein kinase II alpha (CaMKII alpha), and ...
Chronic intracerebroventricular NGF administration improves working memory in young adult memory deficient rats
Jakubowska-Dogru, E; Gumusbas, U (Elsevier BV, 2005-07-01)
Although the beneficial effects of nerve growth factor (NGF) in age-related memory deficits are well documented, the therapeutic role of this neurotrophin in memory deficits occurring in young Subjects remains unclear. In the present study, the effect of chronic NGF administration on spatial working memory was investigated in young adult memory deficient Wistar rats. Memory deficient rats were selected on the basis of their preoperative performance in delayed matching-to-position task (DMTP) carried out in ...
The structural effects of Vitamin A deficiency on biological macromolecules due to ethanol consumption and withdrawal: An FTIR study with chemometrics
ELİBOL, BİRSEN; Severcan, Mete; Jakubowska-Dogru, Ewa; DURSUN, İLKNUR; Severcan, Feride (2022-04-01)
The structural effects of vitamin A-deficiency were examined on the molecular profiles of biomolecules of male rat hippocampus during prolonged ethanol intake/withdrawal using FT-IR spectroscopy coupled with chemometrics. Liquid ethanol diet with/without vitamin A was maintained to adult rats for 3-months. The rats were decapitated at different ethanol withdrawal times and FT-IR spectra were obtained. Ethanol consumption/withdrawal produced significant changes in proteins' conformations, while having insign...
Neuroprotective Efficacy of the Peroxisome Proliferator-Activated Receptor-gamma Ligand in Chronic Cerebral Hypoperfusion
SAYAN ÖZAÇMAK, HALE; SAYAN, Hale; BARUT, FİGEN; Jakubowska-Dogru, Ewa (Bentham Science Publishers Ltd., 2011-08-01)
Chronic cerebral hypoperfusion can cause learning and memory impairment and neuronal damage resembling the effects observed in vascular dementia. PPAR-gamma agonists were shown to modulate inflammatory response and neuronal death following cerebral ischemia. The present study was designed to evaluate possible neuroprotective effects of rosiglitazone, a PPAR-gamma agonist, in rat model of chronic cerebral hypoperfusion. Cerebral hypoperfusion was induced by permanent bilateral occlusion of the common carotid...
Impact of antibiotic induced gut microbiota alteration on cognitive abilities and behaviours of mice
Ceylani, Taha; Gözen, Ayşe Gül; Doğru, Ewa; Department of Biology (2018)
Recently arising studies with animal models show that there is a bidirectional communication between gut microbiota and central nervous system (CNS) through neural, endocrine and immune pathways which influences brain function and behavior. Apparently, gut microbiota may play a role in the regulation of anxiety, mood, cognition, and pain sensation. Gut microbiota may cause gastrointestinal disorders, such as irritable bowel syndrome (IBS), which can be comorbid with stress-related psychiatric conditions inf...
Citation Formats
T. Ceylani, E. Jakubowska-Dogru, R. Gurbanov, H. T. Teker, and A. G. Gözen, “The effects of repeated antibiotic administration to juvenile BALB/c mice on the microbiota status and animal behavior at the adult age,” HELIYON, pp. 0–0, 2018, Accessed: 00, 2020. [Online]. Available: