Caffeine affects the neurobehavioral impact of sodium benzoate in adolescent rats.

The continuous high intake of caffeinated products may harm CNS. Sodium benzoate (SB), broadly used for food preservation, may also have an impact. The current research studied the influence of caffeine and two doses of SB during adolescence period on behavior and brain alterations. Adolescent rats (90-120 gm) were exposed to vehicle, SB 100 and 400 mg/kg, p.o, caffeine (30 mg/kg, i.p), SB 100 or 400 + caffeine for 28 days. Locomotor performances were assessed by the open field, learning and memory were considered with novel object and y-maze, while anxiety was evaluated by light and dark as well as successive allays tests. The results showed that the motor activity of adolescent rats increased with each single treatment. Recognition memory was improved by SB100 and its combination with caffeine while working memory was reduced by SB (100 or 400) combination with caffeine compared with caffeine group. The anxiolytic effect of caffeine was reduced by SB co-treatment in either dose. Concerning biochemical study in the frontal cortex and hippocampus, oxidative biomarkers as well as Cholinesterase content were elevated due to SB400 + caffeine. Dopamine content was almost elevated by all treatments in both regions while GABA content was increased in the frontal cortex only. The obtained results pointed to histopathological changes as a result of brain oxidative stress and undesirable working memory consequences due to caffeine administration with SB, mostly the large dose. The outcomes propose new recommendations to evade the consolidation between processed nourishment and caffeinated beverages during adolescence.

Targeting Autophagy, Apoptosis, and Oxidative Perturbations with Dapagliflozin Mitigates Cadmium-Induced Cognitive Dysfunction in Rats.

Cognitive decline and Alzheimer-like neuropathology are common manifestations of cadmium toxicity. Thanks to its antioxidant/anti-apoptotic features, dapagliflozin has demonstrated promising neuroprotective actions. However, its effect on cadmium-induced neurotoxicity is lacking. The present work aimed to examine whether dapagliflozin could protect rats from cadmium-evoked cognitive decline. In this study, the behavioral disturbances and hippocampal biomolecular alterations were studied after receiving dapagliflozin. Herein, cadmium-induced memory/learning decline was rescued in the Morris water maze, novel object recognition task, and Y-shaped maze by dapagliflozin. Meanwhile, the hippocampal histopathological abnormalities were mitigated. The molecular mechanisms revealed that dapagliflozin lowered hippocampal expression of p-tau and Aß42 neurotoxic proteins while augmenting acetylcholine. The cognitive enhancement was triggered by hippocampal autophagy stimulation, as indicated by decreased SQSTM-1/p62 and Beclin 1 upregulation. Meanwhile, a decrease in p-mTOR/total mTOR and an increase in p-AMPK/total AMPK ratio were observed in response to dapagliflozin, reflecting AMPK/mTOR cascade stimulation. Dapagliflozin, on the other hand, dampened the pro-apoptotic processes in the hippocampus by downregulating Bax, upregulating Bcl-2, and inactivating GSK-3ß. The hippocampal oxidative insult was mitigated by dapagliflozin as seen by lipid peroxide lowering, antioxidants augmentation, and SIRT1/Nrf2/HO-1 pathway activation. In conclusion, dapagliflozin's promising neuroprotection was triggered by its pro-autophagic, anti-apoptotic, and antioxidant properties.

Neurobehavioral effects of alcohol in overcrowded male adolescent rats.

Being a critical neurodevelopmental stage that is affected by social conditions, the period of adolescence was chosen as the age of examining possible modification of alcohol neurobehavioral effects by overcrowding. Adolescent male rats (postnatal day 35±1) were subjected to overcrowding and/or injected with ethanol, 2 g/kg, 20% w/v, (i.p.) for one week. 24 h after the last dose, motor, exploratory behavior, sociability and fear responses were assessed using open field, social interaction and defensive probe burying tests, respectively. Wet brain tissue nitric oxide and reduced glutathione contents as well as monoamine levels, namely dopamine, norepinephrine and serotonin, in addition to 5-HIAA were estimated. Overcrowding increased social play and freezing time. Alcohol administration under overcrowding condition impaired sociability and interfered with active fear response. Alcohol in normal or in under overcrowding condition, impaired motor and exploratory behavior and increased anxiety. These results indicate that concomitant exposure of male adolescent rats to overcrowding and alcohol induced adverse behavioral changes.