Vinpocetine halts ketamine-induced schizophrenia-like deficits in rats: impact on BDNF and GSK-3β/β-catenin pathway

Abstract

There are increasing evidences supporting the involvement of oxidative stress and neuroinflammation in schizophrenia. Vinpocetine, a nootropic phosphodiesterase-1 inhibitor, was proven to possess anti-oxidant and anti-inflammatory potentials. This research aimed to reveal the likely protective features of vinpocetine against ketamine-induced schizophrenia-like deficits in rats. Additionally, the probable mechanisms contributing to this neuroprotection were also elucidated. Vinpocetine was given (20 mg/kg, i.p.) once a day for 14 days commencing 7 days before administrating ketamine (25 mg/kg i.p.). Risperidone was applied as a reference antipsychotic. Vinpocetine pre-treatment revealed a marked amendment in the hyperlocomotion, anxiety, and short-term memory deficits induced by ketamine in rats. In rats' hippocampus, ketamine induced a drastic increase in tissue levels of dopamine, lipid peroxidation, and pro-inflammatory cytokines along with a significant decrease in glutamate, GABA, SOD, and total anti-oxidant capacity. Also, ketamine induced a reduced level of BDNF together with the potentiation of GSK-3β/β-catenin pathway that led to the destruction of β-catenin. Pre-treatment of ketamine-challenged animals with vinpocetine significantly attenuated oxidative stress, inflammation, and neurotransmitter alterations. Vinpocetine also elevated BDNF expression and prevented ketamine-induced stimulation of the GSK-3β/β-catenin signaling. This research presents enlightenments into the role of vinpocetine in schizophrenia. This role may be accomplished through its effect on oxidative stress, inflammation as well as modulating BDNF and the GSK-3β/β-catenin pathway.

Vinpocetine and Ischemic Stroke

“…These events lead to reduction of cAMP system which is important in the expression and regulation of brain derived neurotrophic factor (BDNF), which improves neuronal survival. PDE1 is mainly localized in striatum and cortex which participating in the regulation of neuronal motor activity [17,18].…”

Role of vinpocetine in ischemic stroke and poststroke outcomes: A critical review

“…PDE1 is mainly localized in striatum and cortex which participating in the regulation of neuronal motor activity. [17,18] Indeed, VPN increases neuronal cGMP through inhibition of calmodulin-dependent phosphodiesterase which improves cerebral blood flow and oxygen consumption. [19] VPN improves cerebral metabolism through enhancing glucose and oxygen supply and ATP production by cerebral vasodilation.…”

Vinpocetine amended prenatal valproic acid induced features of ASD possibly by altering markers of neuronal function, inflammation, and oxidative stress

“…Vinpocetine has been shown to correct primary deficits such as social behavior and repetitive behavior in a rodent model of entorhinal cortex lesion (Nyakas et al, 2009). Also, behavioral deficits, such as anxiety, hyperactivity/hyper‐locomotion and nociception were found to be mitigated in murine models of, schizophrenia, attention deficit hyperactivity disorder and inflammatory pain (Abreu‐Villaça et al, 2018; Ahmed et al, 2018; Ruiz‐miyazawa, Pinho‐ribeiro, et al, 2015). Further, PDE1 inhibition is known to ameliorate several neurochemical deficits, such as brain inflammation, brain oxidative stress and neuronal dysfunction, in rodent models of fetal alcohol syndrome, Huntington's disease and early ethanol exposure (Gupta & Sharma, 2014; Krahe et al, 2009; Swart et al, 2017).…”