Crocin acts as a neuroprotective mediator against methylphenidate-induced neurobehavioral and neurochemical sequelae: Possible role of the CREB-BDNF signaling pathway

Abstract

Methylphenidate (MPH) abuse causes adverse neurobehavioral and neurochemical effects. Some herbal components such as crocin have shown neuroprotective properties. The current study evaluates the potential role of the cyclic AMP response element binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling pathway in mediating the neuroprotective effects of crocin against MPH-induced neurotoxicity in rats. Seventy adult male rats were randomly divided into seven groups. Group 1 and 2 received 0.7 ml/rat of normal saline and 10 mg/kg of MPH, respectively. Groups 3, 4, 5, and 6 were treated simultaneously with MPH (10 mg/kg) and crocin (10, 20, 40, and 80 mg/kg, respectively) for 21 days. Group 7 was treated with crocin (80 mg/kg) alone for 21 days. The Morris water maze (MWM) and open field test were used to assess cognitive and locomotor activities. Hippocampal neurotoxicity parameters and levels of BDNF and CREB were evaluated. Simultaneous treatment with various doses of crocin reduced the MPH-induced cognition disturbances and hyperlocomotion. In addition, lipid peroxidation increased with MPH treatment and levels of the oxidized forms of glutathione (GSSG), interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and Bax increased. MPH treatment decreased levels of the reduced form of glutathione (GSH), P-CREB, Bcl-2, and BDNF in the hippocampus. MPH also reduced activity of superoxide dismutase, glutathione peroxidase, and glutathione reductase in the hippocampus. In contrast, crocin attenuated MPH-induced oxidative stress, inflammation, and apoptosis, and increased levels of P-CREB and BDNF. Thus, crocin-likely via stimulation of the P-CREB/BDNF signaling pathway-displayed neuroprotection against MPH-induced neurotoxicity.

Roflumilast Ameliorates Isoflurane-Induced Inflammation in Astrocytes via the CREB/BDNF Signaling Pathway

“…The inactivation of protein kinase (PKA) is blocked by the suppression of cAMP, which further hinders the activation of phosphorylated CREB. , It is reported that the CREB family transcription factors are major mediators of BDNF transcriptional autoregulation in cortical neurons . Ebrahimzadeh also reported that BDNF induced by the phosphorylation of CREB mediates the neuroprotective effects of crocin against MPH-induced neurotoxicity . Therefore, the cAMP/CREB/BDNF signaling pathway might be an effective target for the neuroprotective purpose.…”

“…22 Ebrahimzadeh also reported that BDNF induced by the phosphorylation of CREB mediates the neuroprotective effects of crocin against MPH-induced neurotoxicity. 23 Therefore, the cAMP/CREB/BDNF signaling pathway might be an effective target for the neuroprotective purpose.…”

Investigating the effect of crocin on memory deficits induced by total sleep deprivation (TSD) with respect to the BDNF, TrkB and ERK levels in the hippocampus of male Wistar rats

“…In a previous study, crocin enhanced BDNF level in epidermal neural crest stem cells (Baharvand et al, 2020). Crocin via stimulating the CREB/BDNF signaling pathway induces a neuroprotective effect (Ebrahimzadeh et al, 2019). In addition, crocin increases the level of BDNF in a rat model of neuropathic pain (Safakhah et al, 2020).…”

Adenosine A2A Receptor Blockade Ameliorates Mania Like Symptoms in Rats: Signaling to PKC-α and Akt/GSK-3β/β-Catenin

“…The remaining rats (n = 45) received a daily injection of MPH (5 mg/kg, i.p.) [ 25 , 26 ] and recorded as diseased rats. Continuous injection of MPH altered behavioral activity as displayed in the open field (OFT) and forced swim (FST) tests on the 9 th day.…”