Tetrahydropalmatine Regulates BDNF through TrkB/CAM Interaction to Alleviate the Neurotoxicity Induced by Methamphetamine

Abstract

Tetrahydropalmatine (THP) has analgesic, hypnotic, sedative, and other pharmacological effects. Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity, growth, and development. However, their mechanism of action in methamphetamine (MA)-induced neurotoxicity remains unclear. This study aims to explore the important role of BDNF in MA neurotoxicity and whether THP can regulate BDNF through the interaction between tyrosine kinase receptor B (TrkB)/calmodulin (CAM) to alleviate the neurotoxicity induced by MA. SD rats were randomly divided into control, MA, and MA + THP groups. Stereotyped behavior test, captive rejection test, open field test (OFT), and Morris water maze (MWM) were used to evaluate the anxiety, aggression, cognition, learning, and memory. Extracted hippocampus and mesencephalon tissue were detected by Western blot, HE staining, and immunohistochemistry. TUNEL staining was used to detect apoptosis. MOE was used for bioinformatics prediction, and coimmunoprecipitation was used to confirm protein interactions. Long-term abuse of MA resulted in lower weight gain ratio and nerve cell damage and caused various neurotoxicity-related behavioral abnormalities: anxiety, aggression, cognitive motor disorders, and learning and memory disorders. MA-induced neurotoxicity is related to the down-regulation of BDNF and apoptosis. THP attenuated the MA-induced neurotoxicity by decreasing CAM, increasing TrkB, phosphorylating Akt, up-regulating NF-κB and BDNF, and inhibiting cell apoptosis. MA can induce neurotoxicity in rats. BDNF may play a vital role in MA-induced neurotoxicity. THP regulates BDNF through TrkB/CAM interaction to alleviate the neurotoxicity induced by MA. THP may be a potential therapeutic drug for the neurotoxic and neurodegenerative diseases related to MA.

Prelimbic cortex dynorphin/κ opioid receptor system modulates methamphetamine‐induced cognitive impairment

“…Since METH exposure can also lead to poor performances in other cognitive phenotypes, 35,37–39 we also conducted a Y‐maze test to further confirm the neuroprotective effects of KOR antagonist (Figure 7A,B). We found that METH decreased number (Figure 7E, F (2, 33) = 6.921, p = 0.0031) and rate of spontaneous alteration (SAP) (Figure 7F, F (2, 33) = 13.33, p < 0.0001) and increased incorrect same arms returns (SAR) (Figure 7D, F ((2, 33) = 4.995, p = 0.0127), which was reserved by norBNI microinjections into PL before METH treatment.…”

“…Since METH exposure can also lead to poor performances in other cognitive phenotypes, 35,[37][38][39] we also conducted a Y-maze test to further confirm the neuroprotective effects of KOR antagonist (Figure 7A,B). We found that METH decreased number (Figure 7E, F The medial prefrontal cortex (mPFC) is a crucial brain region involved in cognition.…”

Dexmedetomidine pretreatment alleviates ropivacaine-induced neurotoxicity via the miR-10b-5p/BDNF axis

“…BDNF reduces the apoptosis of neurons submitted to oxygen–glucose deprivation/reoxygenation [ 47 ] and promotes neuronal survival after neonatal hypoxic-ischemic encephalopathy [ 48 ]. Moreover, the manipulation of the BDNF/TrkB pathway contributes to reversing neuronal apoptosis and alleviating neurotoxicity induced by methamphetamine [ 23 ] and propofol [ 49 ]. The upregulation of miR-10b-5p results in the decrease of BDNF levels in mouse hippocampal neurogenesis and cognitive impairment model [ 18 ].…”

“…Thus, manipulating BDNF pathways represents a viable treatment approach to a variety of neurological and psychiatric disorders [ 22 ]. Upregulation of BDNF has been demonstrated to inhibit neuronal apoptosis and alleviate neurotoxicity induced by methamphetamine [ 23 ]. Accordingly, we speculated whether DEX pretreatment can upregulate BDNF expression through miR-10b-5p to regulate neuronal viability and protect against ropivacaine-induced neurotoxicity.…”

Regulation and bioinformatic analysis of circ_0015891/miR-129-1-3p axis in methamphetamine-induced dopaminergic apoptosis

“…A research report noted that rat brains exhibited significant increases in time- and location-dependent BNDF and NTRK2 expression following binge-like METH exposure (4 x 4 mg/kg, s.c., 2 h (h) apart) ( 34 ). Another study concluded that high expression of BDNF and NTRK2 contributed to the reduction of METH-induced apoptosis ( 35 ). Combined with the 2 studies, it is reasonable to speculate that the high concentration of circ_0015891 could sponge miR-615-5p to disinhibit NTRK2 ( Table 1 ), contributing to protect dopaminergic cells from apoptosis.…”