RESUMEN
AIMS: Methamphetamine (METH) has become a major public health problem because of its abuse and profound neurotoxic effects, causing alterations in brain structure and function, and impairing cognitive functions, including attention, decision making, emotional memory, and working memory. This study aimed to determine whether melatonin (MEL), the circadian-control hormone, which has roles beyond circadian rhythm regulation, could restore METH-induced cognitive and neuronal impairment. MAIN METHODS: Mice were treated with either METH (1 mg/kg) or saline for 7 days, followed by MEL (10 mg/kg) or saline for another 14 days. The Morris water maze (MWM) test was performed one day after the last saline or MEL injection. The hippocampal neuronal density, synaptic density, and receptors involved in learning and memory, along with downstream signaling molecules (NMDA receptor subunits GluN2A, GluN2B, and CaMKII) were investigated by immunoblotting. KEY FINDINGS: METH administration significantly extended escape latency in learning phase and reduced the number of target crossings in memory test-phase as well as decreased the expression of BDNF, NMDA receptors, TrkB receptors, CaMKII, ßIII tubulin, and synaptophysin. MEL treatment significantly ameliorated METH-induced increased escape latency, decreased the number of target crossings and decreased expression of BDNF, NMDA receptors, TrkB receptors, CaMKII, ßIII tubulin and synaptophysin. SIGNIFICANCE: METH administration impairs learning and memory in mice, and MEL administration restores METH-induced neuronal impairments which is probably through the changes in BDNF, NMDA receptors, TrkB receptors, CaMKII, ßIII tubulin and synaptophysin. Therefore, MEL is potentially an innovative and promising treatment for learning and memory impairment of humans.
Asunto(s)
Hipocampo/efectos de los fármacos , Melatonina/farmacología , Trastornos de la Memoria/tratamiento farmacológico , Metanfetamina/toxicidad , Animales , Estimulantes del Sistema Nervioso Central/toxicidad , Cognición/efectos de los fármacos , Hipocampo/patología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Trastornos de la Memoria/inducido químicamente , Ratones , Ratones Endogámicos ICR , Neuronas/efectos de los fármacos , Neuronas/patologíaRESUMEN
Serious cutaneous adverse drug reactions [i.e., SJS/TEN with severe ocular complications (SOC)] associated with cold medicine (CM) were reported in several studies. To assess the risks of CM-induced SJS/TEN with SOC, systematic review and meta-analysis were employed. Studies investigating associations between HLA genotypes and CM-induced SJS/TEN with SOC were systematically searched in PubMed, Scopus and the Cochrane Library. Overall odds ratios (ORs) with 95% CIs were calculated using a random-effects model to determine these associations. An initial search of the databases identified 24,011 articles, of which 6 studies met the inclusion criteria. In total from all studies, associations between 81 different HLA genotypes and CM-induced SJS/TEN with SOC (i.e., 22 different HLA-A genotypes, 40 different HLA-B genotypes and 19 different HLA-C genotypes) were investigated. Risk factors to develop SJS/TEN with SOC in patients who used CM were identified from our meta-analysis. HLA-A*0206 (OR = 3.90; 95% CI = 1.96-7.77), HLA-A*3303 (OR = 2.28; 95% CI = 1.31-3.97), HLA-B*4403 (OR = 3.27; 95% CI = 1.52-7.03) and HLA-C*0501 (OR = 2.55; 95% CI = 1.19-5.44) were associated with CM-induced SJS/TEN with SOC. With our results demonstrating a significant association between using of CMs and the severe ADR, a genetic testing can be helpful. However, the CMs are commonly used as an over-the-counter drug in practically almost of people in populations worldwide, the genetic screening prior to use of the CMs might not be cost-effective. Nonetheless, for people with a family history of developing the ADRs with a possible involvement of CMs, a genetic screening may be beneficial.