Containment of neuroimmune challenge by diosgenin confers amelioration of neurochemical and neurotrophic dysfunctions in ketamine-induced schizophrenia in mice

Brain Disorders, Journal Year: 2024, Volume and Issue: 13, P. 100122 - 100122

Published: Feb. 9, 2024

Inhibition of neuroinflammation through N-methyl-D-aspartate receptor (NMDAR) regulation can provide normalization neurochemical homeostasis and neurotrophic support in the pathogenesis psychiatric disorders with complex symptoms such as schizophrenia. Accordingly, preventive reversal effects potential mechanisms diosgenin, a phyto-steroidal sapogenin anti-inflammatory functions, was evaluated ketamine (an NMDAR antagonist) model schizophrenia mice. Adult male mice were allotted into 5 groups. In protocol, received saline (10 mL/kg), diosgenin (25 50 mg/kg) risperidone (0.5 orally for 14 days, additional injection (20 mg/kg/day/i.p.) from days 8-14. took consecutively prior to treatments Thereafter, schizophrenia-like behavior, therapeutic extrapyramidal adverse effect, neuroimmune, consequences important brain areas affected disorder assayed. Diosgenin prevents reverses stereotypy cognitive impairment, psychotic-depression relative Complementarily, ketamine-induced dopamine serotonin alterations striatum, prefrontal-cortex, hippocampus. Except cortical regions, prevented reversed depletions glutamic acid decarboxylase these regions by ketamine, suggesting improved GABAergic system. Additionally, elevation neuroinflammatory markers: myeloperoxidase, tumor necrosis factor-alpha interleukin-6, inhibited Also, levels factor three both protocols respectively. Among other mechanisms, antipsychotic effect might be associated attenuation neuroimmune alterations.

Language: Английский

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Diosgenin reverses posttraumatic stress disorder in mice by augmenting neurochemical release and inhibiting HPA axis dysfunction, oxidative stress, and neuroinflammation

Journal of Affective Disorders Reports, Journal Year: 2024, Volume and Issue: 17, P. 100814 - 100814

Published: June 26, 2024

Post-traumatic stress disorder (PTSD) is a mental linked to neurochemical, hypothalamic-pituitary-adrenal (HPA)-axis dysregulations, inflammatory and pro-oxidant challenges in response traumatic events. It one of the leading causes neurocognitive declines, hence prompting need for pharmacological intervention. However, impact diosgenin, naturally occurring steroidal saponin with adaptogenic-like action, on PTSD-induced neuropsychiatric disturbances its underlying mechanisms are unknown. In this study, we investigated outcome diosgenin treatment multimodal traumatic, single prolonged (SPS)-induced PTSD mice. Following SPS-induced 7 days PTSD, mice (n = 9) were thereafter treated (25 50 mg/kg) or fluoxetine (10 orally from 8–20 (14 days). Locomotory, cognitive-, depressive- anxiety-like behaviors investigated. We assayed changes adrenal weight, serum glucose corticosterone concentrations. Neurochemical, inflammatory, oxido-nitrergic dysfunctions monoamine oxidase-B acetylcholinesterase activities, measured striatum, prefrontal-cortex hippocampus. The results revealed that SPS challenge inhibited locomotor, spatial/non-spatial memory functions, increased anxiety depressive-like features, which reversed by diosgenin. Diosgenin reduced oxidase-B, TNF-α, IL-6, malondialdehyde nitrite levels Antioxidants such as glutathione, superoxide-dismutase, catalase SPS-mice brains Moreover, attenuated hyper-HPA-axis mediation decreasing corticosterone, gland hypertrophy. Herewith, suggest convenes protection against exposed enhancing antioxidant machinery, neurochemical modulations, inhibition oxido-nitrergic, HPA-axis dysfunctions.

Language: Английский

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Adverse hematological profiles associated with chlorpromazine antipsychotic treatment in male rats: Preventive and reversal mechanisms of taurine and coenzyme-Q10

Toxicology Reports, Journal Year: 2024, Volume and Issue: 12, P. 448 - 462

Published: April 21, 2024

Chlorpromazine (CPZ) is one of the most effective antipsychotic drugs used for managing psychotic related disorders owing to its dopamine receptor blocking action. However, pharmacological investigations against CPZ's cytotoxic effect have remained scarce. Hence, this study investigated preventive and reversal effects taurine coenzyme-Q10 (COQ-10), which are compounds with proven natural antioxidant properties, CPZ-induced hematological impairments in male rats. In study, rats received oral saline (10 mL/kg), (150 mg/kg/day), COQ-10 mg/kg/day) or combination 56 days, alongside CPZ (30 mg/kg, p.o.) between days 29-56. protocol, had repeatedly before treatments their from Rats were also given alone days. Thereafter, serums extracted assayed hematological, oxidative inflammatory markers. induced decreased red/white blood cells, erythropoietin, platelet count, packed cell volume hemoglobin, neutrophil, lymphocyte, prevented reversed by COQ-10, combination. Taurine improved mean corpuscular volume, hemoglobin concentration, increased erythropoietin levels relative groups. malondialdehyde, tumor necrosis factor-alpha interleukin-6 interleukin-10, glutathione, superoxide-dismutase comparison notably antioxidant/anti-inflammatory status controls. Among other mechanisms, abated deficiencies, via serum stress, pro-inflammatory cytokines release, antioxidants anti-inflammation function.

Language: Английский

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Effective Action of Silymarin against Ketamine-induced Schizophrenia in Male Mice: Insight into the Biochemical and Molecular Mechanisms of Action

Journal of Psychiatric Research, Journal Year: 2024, Volume and Issue: 179, P. 141 - 155

Published: Sept. 13, 2024

Language: Английский

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Effects of combined postweaning social isolation and ketamine administration on schizophrenia-like behaviour in male Sprague Dawley rats

Behavioural Brain Research, Journal Year: 2024, Volume and Issue: 476, P. 115214 - 115214

Published: Aug. 24, 2024

The pathophysiology behind negative and cognitive symptoms of schizophrenia is not well understood, thus limiting the effectiveness treatment on these symptoms. Developing reliable animal model vital to advance our understanding neurobiological basis disorder. Double hit used refer use two inducing interventions viz ketamine exposure social isolation. In this study we aim investigate robustness double in schizophrenia. On postnatal day (PND) 23, thirty-two male Sprague Dawley rats were randomly grouped into four equal groups as follows: group housed + saline (GH), (GHK), isolated (SI), (SIK). A single dose (16 mg/kg) was administered 3 times a week for weeks. Isolated animals singly throughout study. following behavioural tests carried out: elevated plus maze, three chamber interaction, resident intruder tests, novel object recognition (NOR). SIK exhibited high anxiety levels, with increased ACTH, corticosterone norepinephrine concentration when compared other groups. also presented reduced interaction decreased oxytocin concentration. more aggressive towards juvenile but had low testosterone or showed impaired visual learning memory expression proinflammatory cytokines. This suggest that robust than each alone.

Language: Английский

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Ketamine-Induced Behavioral Perturbations, Redox Imbalances, and Neurotransmitter Deficits in Mice: The Preventive and Reversal Neuromodulatory Potential of Diosmin as an Antipsychotic

Brain Disorders, Journal Year: 2025, Volume and Issue: unknown, P. 100210 - 100210

Published: March 1, 2025

Language: Английский

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Urolithin A alleviates schizophrenic-like behaviors and cognitive impairment in rats through modulation of neuroinflammation, neurogenesis, and synaptic plasticity

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 26, 2025

Cognitive impairment in schizophrenia occurs the early stages of disease and is closely associated with prognosis. Alleviation cognitive faces major challenges owing to lack preventive therapeutic drugs that are novel effective. Urolithin A (UA) a gut microbial metabolite ellagic acid has demonstrated neuroprotective effects multiple neurological models. Nonetheless, neuromodulatory role UA yet be elucidated. Wistar rat pups were separated from their mothers for 24 h on postnatal days (PNDs) 9–10 establish an early-life stress model. The pretreated at different administration times (2, 4, 6 weeks) doses (50, 100, 150 mg/kg) adolescence (PND29). Behavioral tests performed after end administration. Subsequently, hippocampal samples collected histopathological molecular evaluations. Male offspring rats subjected maternal separation exhibited increased sensitivity prepulse inhibition impairment, accompanied by severe neuroinflammation impaired neurogenesis. However, attenuated separation-induced deficits impairments restored neurogenesis dose-dependent manner. Furthermore, pretreatment preserved dendritic spine density, synapses, presynaptic vesicles. In addition, it exerted anti-inflammatory inhibiting microglial activation expression proinflammatory cytokines tumor necrosis factor-α, interleukin-6, interleukin-1β. Potential mechanisms included upregulation brain-derived neurotrophic factor protein extracellular signal-regulated kinase signaling pathway. This study first preclinical evaluation schizophrenia. findings suggest changes function linked driven interaction among neuroinflammation, neurogenesis, synaptic plasticity potential reverse these processes. These observations provide evidence future clinical trials as dietary supplement preventing

Language: Английский

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PROTECTIVE EFFECT OF CILOSTAZOL AGAINST KETAMINE-INDUCED BIOCHEMICAL AND BEHAVIORAL PHENOTYPE OF SCHIZOPHRENIA IN MICE

Asian Journal of Pharmaceutical and Clinical Research, Journal Year: 2025, Volume and Issue: unknown, P. 230 - 237

Published: April 7, 2025

Objective: Schizophrenia (SCZ), a mental illness affecting 1% of the world population, is characterized by extensive structural and functional brain changes. It brought on confluence psychological, environmental, hereditary variables. frequently coexisted with other diseases, lowering quality life increasing risk early death. The objective this research to explored potential cilostazol (Phosphodiesterase-3 inhibitor) in ketamine (KET)-induced SCZ -like behavioral biochemical alterations mice. Methods: In mice, was induced injecting KET (30 mg/kg; i.p.) for 10 days row. Different parameters such as immobility time (Forced swim test), locomotor anxiety (open field cognitive dysfunction (Morris water maze), social interactions, catalepsy were examined. Histopathological changes (lipid peroxides, glutathione [GSH], acetylcholinesterase [AChE] activity) also Cilostazol (25 50 p.o.) test clozapine (7.5 mg/kg p.o.), standard drug used investigation. Tukey’s multiple comparison one-way analysis variance statistical all findings. p<0.050 regarded statistically significant. Results: Significant (p<0.05) have been observed following 28 treatment (increased time, impaired anxiety-like behaviors, dysfunction, catalepsy). Increased oxidative stress (higher lipid peroxides decreased GSH), AChE activity, histopathological noted significantly -treated corrected histological changes, alterations, problems. Conclusion: As per behavioral, histopathological, outcomes, we can draw conclusion that may provide neurodefensive effects against -induced

Language: Английский

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Investigation of the Protective Effects of Aripiprazole on Methylphenidate-induced Neurotoxicity in Rats

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Language: Английский

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Adaptogenic action of diosgenin againsts chronic unpredictable mild stress-induced neuroimmune dysfunction of HPA axis reverses psychiatric behavior in mice

Deleted Journal, Journal Year: 2024, Volume and Issue: 5(2), P. 200148 - 200148

Published: April 27, 2024

Language: Английский

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