MAIN METHODS: Neuroblastoma cell line SH-SY5Y was treated with β-amyloid (Aβ) to induce AD-like pathological changes, which serves as Alzheimer's disease model. Tβ4 was overexpressed in SH-SY5Y cells by lentivirus infection, and downregulated by siRNA transfection. Apoptosis of transfected SH-SY5Y cells after Aβ-treatment was examined by western blot and flow cytometry. Apoptotic proteins and Tβ4-related signaling pathways were also investigated by western blot.
KEY FINDINGS: We found that Tβ4 overexpression increased viability and suppressed apoptosis of Aβ-treated SH-SY5Y cells. Tβ4 ameliorated oxidative damage and suppressed reactive oxygen species production in Aβ-treated SH-SY5Y cells. Consistently, Tβ4 overexpression down-regulated the expression levels of pro-apoptotic markers such as Caspase-3, Caspase-8, and Bax, while up-regulated the expression level of anti-apoptotic gene Bcl-2 in Aβ-stimulated SH-SY5Y cells. Mechanistically, we demonstrated that Tβ4 dampened ERK/p38 MAPK signaling and enhanced 5-HTR1A expression in Aβ-treated SH-SY5Y cells. Moreover, we revealed that Tβ4 inhibited the activation of ERK pathway through up-regulating 5-HTR1A in Aβ-treated SH-SY5Y cells.
SIGNIFICANCE: Taken together, our findings provide evidences to support the neuroprotective role of Tβ4 and might open up new therapeutic applications of Tβ4 in AD treatment.
MAIN METHODS: Male Sprague-Dawley rats were fed with either normal diet or high-fat diet for 8weeks. Firstly, OB rats were divided into (1) OB and (2) OB+R (100mg/kg, p.o, 28days). Then, OB rats were subjected to MI (ISO, 85mg/kg, s.c, 2days) and divided into three groups: (1) OB+MI, (2) OB+MI+R and (3) OB+MI+enalapril for another 4weeks.
KEY FINDINGS: Roselle ameliorated OB and OB+MI's cardiac systolic dysfunction and reduced cardiac hypertrophy and fibrosis. The increased oxidative markers and decreased antioxidant enzymes in OB and OB+MI groups were all attenuated by roselle.
SIGNIFICANCE: These observations indicate the protective effect of roselle on cardiac dysfunction in OB and OB+MI rats, which suggest its potential to be developed as a nutraceutical product for obese and obese patients with MI in the future.
AIMS: The present study is focused on evaluating the role of ambrisentan (selective endothelin-A receptor antagonist) on cigarette smoke-induced cognitive impairment in Danio rerio.
MAIN METHODS: The cognitive dysfunction was developed by cigarette smoke exposure (CSE; 10 min in 25 ml of CSE per day) for five days. The selective endothelin-A receptor antagonist i.e., ambrisentan (2.5 to 5 mg/kg; i.p. for five consecutive days) was used for testing of CSE induced cognitive dysfunction. In addition, treatment of reference drug i.e., donepezil (10 mg/kg; i.p. for five consecutive days) was used for this cognitive function study. The cognitive functions were assessed by light and dark chamber; color recognition; partition preference; horizontal compartment; and T-Maze tests. Further, the CSE induced biomarkers changes of the zebrafish brain samples were estimated.
KEY FINDINGS: The treatment of ambrisentan showed a potential ameliorative effect against the CSE induced cognitive functions along with attenuation of biochemical changes. The results are comparable to donepezil-treated groups.
SIGNIFICANCE: Therefore, ambrisentan can be considered for the attenuation of CSE induced impairment neurocognitive functions due to its reduction of free radical scavenging and neuroinflammatory actions as well as regulation of cholinergic neurotransmitter functions.
AIMS: In this updated comprehensive review, we discuss the emerging implication of mutations in neurotransmitter-mediated receptors and ion channels. We aim to provide critical findings of the current literature about the role of neurotransmitters in epilepsy.
MATERIALS AND METHODS: A comprehensive literature review was conducted to identify and critically evaluate studies analyzing the possible relationship between epilepsy and neurotransmitters. The PubMed database was searched for related research articles.
KEY FINDINGS: Glutamate and gamma-aminobutyric acid (GABA) are the main neurotransmitters playing a critical role in the pathophysiology of this balance, and irreversible neuronal damage may occur as a result of abnormal changes in these molecules. Acetylcholine (ACh), the main stimulant of the autonomic nervous system, mediates signal transmission through cholinergic and nicotinic receptors. Accumulating evidence indicates that dysfunction of nicotinic ACh receptors, which are widely expressed in hippocampal and cortical neurons, may be significantly implicated in the pathogenesis of epilepsy. The dopamine-norepinephrine-epinephrine cycle activates hormonal and neuronal pathways; serotonin, norepinephrine, histamine, and melatonin can act as both hormones and neurotransmitters. Recent reports have demonstrated that nitric oxide mediates cognitive and memory-related functions via stimulating neuronal transmission.
SIGNIFICANCE: The elucidation of the role of the main mediators and receptors in epilepsy is crucial for developing new diagnostic and therapeutic approaches.