ABSTRACT
Objective To investigate the expression and relationship of canonical transient receptor potential channel-3 (TRPC3) and brain-derived neurotrophic factor (BDNF) in the hippocampus of a rat model of Alzheimer's disease (AD). Methods SD rats were randomly divided into PBS, AD, and AD+BDNF experimental groups. AD models were generated by intracerebroventricular injection ofβ-amyloid protein (Aβ1-42). BDNF was injected via the lateral ventricle catheter after 14 days. The Morris water maze test was used to assess the spatial learning and memory ability of the rats. The expression of TRPC3 and BDNF mRNA and protein in the hippocampus were detected by RT-PCR and Western blotting, respectively. Results The Morris water maze test showed that the escape latencies of the fifth day in the AD group were longer than those in the PBS group (P ＜ 0. 05). The escape latencies in the AD+BDNF group were shorter than those in the AD group (P ＜ 0. 05). RT-PCR and Western blotting results showed that the expression of both TRPC3 and BDNF were reduced in the AD group compared with the PBS group (P ＜ 0. 05). TRPC3 expression was increased in the AD+BDNF group compared with the AD group (P ＜ 0. 05). Conclusion The expression of BDNF and TRPC3 is decreased in the hippocampus of AD rats. An exogenous BDNF injection appears to improve the spatial learning and memory of AD rats that are impaired by a Aβ1-42 injection, possibly via TRPC3 upregulation, and may play a protective role in neurons.
ABSTRACT
The canonical transient receptor potential channels (TRPCs) constitute a series of nonselective cation channels with variable degrees of Ca2+ selectivity. TRPCs consist of seven mammalian members, TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7, which are further divided into four subtypes, TRPC1, TRPC2, TRPC4/5, and TRPC3/6/7. These channels take charge of various essential cell functions such as contraction, relaxation, proliferation, and dysfunction. This review, organized into seven main sections, will provide an overview of current knowledge about the underlying pathogenesis of TRPCs in cardio/cerebrovascular diseases, including hypertension, pulmonary arterial hypertension, cardiac hypertrophy, atherosclerosis, arrhythmia, and cerebrovascular ischemia reperfusion injury. Collectively, TRPCs could become a group of drug targets with important physiological functions for the therapy of human cardio/cerebro-vascular diseases.
Subject(s)
Humans , Arrhythmias, Cardiac , Atherosclerosis , Cardiomegaly , Cardiovascular Diseases , Cerebrovascular Disorders , Hypertension , Hypertension, Pulmonary , Relaxation , Reperfusion Injury , Transient Receptor Potential ChannelsABSTRACT
Objective To investigate the protein expression of the canonical transient receptor potential(TRPC)channel in the hippocampus of amyloidβprotein(Aβ)?induced Alzheimer’s disease(AD)mice. Methods A total of 36 ICR mice were randomly divided into AD group and control group,with 18 rats in each group. AD mice models were established by Aβ1?42 microinjection into the lateral intracerebroventricular. Learning and memory abilities of the mice were determined using Morris water maze. All TRPC1?TRPC7 mRNA levels in the hippocampus of the mice were detected using reverse transcriptase polymerase chain reaction(RT?PCR). Hippocampal TRPC4 protein expression was examined using immunofluorescence and Western blotting methods. Results Water maze test results showed that the escape latency of AD group were significant?ly longer than that of the control group(P<0.01),and that the target quadrant occupancy of AD group was significantly shortened(P<0.01)and the frequency of platform crossing of AD group was significantly reduced(P<0.01). RT?PCR results showed that all TRPC(TRPC1?TRPC7) mRNA were expressed in the hippocampal of both AD group and control group. Among these channels ,only TRPC4 mRNA levels of AD group was higher than that of the control group(P<0.01). Immunofluorescence images showed that TRPC4 expressed on the membrane of neurons and the intensities of the immunofluorescence of TRPC4 in AD group were stronger than that of control group. Western blotting results showed that the TRPC4 protein expression of AD group was higher than that of control group(P<0.05). Conclusion The increase of TRPC4 protein expression in the hippocampus of mice after intracerebroventricular injection of Aβ1?42 oligomers suggests that TRPC4 may be involved in the pathogenesis of AD induced by calcium homeostasis.
ABSTRACT
The canonical transient receptor potential(TRPC)regulating non-voltage-gated cation entry in plasma-membrane is widely expressed in cardiovascular system. Cytosolic Ca2+takes charge of multifunctional biogenic activities and its stabilization is criti?cal for physiological function. Almost all TRPC channels are non-selectively permeable for Ca2+. Overexpression or transgenation of TRPC leading to the change of Ca2+may contribute to fundamental malfunctions and engage in the physiological and pathophysiological processes of some diseases. Evidence suggests that regulation of TRPC channels plays important roles in the development of hyperten?sion,pulmonary arterial hypertension,cardiac hypertrophy,atherosclerosis,and arrhythmia. This review gives an overview of the functional properties of mammalian TRPC channels,describes their roles in cardiovascular diseases and discusses their potential as drug targets for therapeutic intervention.
ABSTRACT
The canonical transient receptor potential(TRPC) regulating non-voltage-gated cation entry in plasma-membrane is widely expressed in cardiovascular system. Cytosolic Ca2+ takes charge of multifunctional biogenic activities and its stabilization is critical for physiological function. Almost all TRPC channels are non-selectively permeable for Ca2+. Overexpression or transgenation of TRPC leading to the change of Ca2+ may contribute to fundamental malfunctions and engage in the physiological and pathophysiological processes of some diseases. Evidence suggests that regulation of TRPC channels plays important roles in the development of hypertension, pulmonary arterial hypertension, cardiac hypertrophy, atherosclerosis, and arrhythmia. This review gives an overview of the functional properties of mammalian TRPC channels, describes their roles in cardiovascular diseases and discusses their potential as drug targets for therapeutic intervention.
ABSTRACT
Objective: To explore the effects of monocrotaline (MCT) on right ventricular function and expression of cardiac canonical transient receptor potential channels (TRPC) subfamily in experimental rats. Methods: The SD male rats were randomly divided into 2 groups:Control group, the rats were normally fed and MCT group, the rats received a single dose injection of MCT 60 mg/kg to induce myocardial hypertrophy. n=10 in each group and all animals were treated for 3 weeks. The right ventricular hemodynamics parameters and right ventricular hypertrophy index (RVHI) were measured, right ventricular myocardium tissue section was observed by HE staining, the mRNA and protein expressions of TRPC subfamily were examined by RT-PCR and Western blot analysis. Results: Compared with Control group, MCT group had increased RVSP, RVHI, RV+dp/dtmax and decreased RV-dp/dtmax, all P Conclusion:Right ventricular hypertrophy could be induced by 3 weeks MCT treatment, it up-regulating the mRNA and protein expressions of TRPC6 which might be involved in the occurrence and development of cardiac hypertrophy in experimental rats.