Coenzyme Q10 reduces expression of apoptotic markers in adult rat nucleus accumbens dopaminergic neurons treated with methamphetamine.

BACKGROUND: Abuse of addictive drugs such as methamphetamine (METH) has become a global problem, leading to many social, economic, and health disturbances, including neurological and cognitive disorders. Neuronal damage is reported in chronic METH abusers. The neuroprotective role of CoQ10 has been shown in many studies. In the present study, we aimed to assess the pre and post-efficacy of CoQ10 on the dopaminergic neurons of the Nucleus Accumbens (de Miranda et al. in Food Res Int 121:641-647, 2019) in the male adult rats treated with METH. METHODS: 80 rats were randomly divided into eight groups (n = 10), including: negative control (intact), positive control (received 5 mg/kg/day METH/IP), three post-treatment groups (METH + 5, 10, 20 mg/kg CoQ10) and three pre-treatment groups (received 5, 10, 20 mg/kg CoQ10 as pre-treatment for 14 days before METH injection). The expression of Bax, Bcl-2, Bax/Bcl-2 ratio, P53, Caspase-3 and tyrosine hydroxylase in NAc studied using western blotting. Nissl staining was used to study the neuronal density of NAc. RESULTS: Our results showed that the different doses of CoQ10 in METH-treated animals significantly changed pro-apoptotic proteins' expression in the benefit of neuronal survival of NAc (P < 0.05). Neuronal density in NAc were significantly lower in the METH group compared to the control and CoQ10 treated groups. Pre- and post-treatment with different doses of CoQ10 restored the neuronal damage in NAc. CONCLUSIONS: CoQ10 could decrease the activation of pro-apoptotic proteins and reduce the neurodegenerative effects induced by METH. From a clinical point of view, it seems that certain antioxidants such as CoQ10 should receive more attention in clinical trial research. We believe that antioxidants could be the promising for drug abuse treatment in the future.

6-OHDA mediated neurotoxicity in SH-SY5Y cellular model of Parkinson disease suppressed by pretreatment with hesperidin through activating L-type calcium channels.

OBJECTIVES: Parkinson's disease (PD) is a neurological condition with selective progressive degeneration of dopaminergic neurons. Routine therapies are symptomatic and palliative. Although, hesperidin (Hsd) is known for its neuroprotective effects, its exact cellular mechanism is still a mystery. Considering the important role of calcium (Ca2+) in cellular mechanisms of neurodegenerative diseases, the present study aimed to investigate the possible effects of Hsd on Ca2+ channels in cellular model of PD and the possible association between the selective vulnerability of neurons in cellular models of PD and expression of the physiological phenotype that changes Ca2+ homeostasis. METHODS: SH-SY5Y cell line was used in this study; cell damage was induced by 150 µM 6-OHDA and the cells' viability was examined using MTT assay. Intracellular calcium, reactive oxygen species (ROS) and mitochondrial membrane potential were determined by the fluorescence spectrophotometry method. The expressions of calcium channel receptors were determined by gel electrophoresis and immunoblotting. RESULTS: Loss of cell viability and mitochondrial membrane potential were confirmed in 6-OHDA treated cells. In addition, intracellular ROS and calcium levels, calcium channel receptors significantly increased in 6-OHDA-treated cells. Incubation of SH-SY5Y cells with hesperidin showed a protective effect, reduced the biochemical markers of cell damage/death, and balanced calcium hemostasis. CONCLUSIONS: Based on our findings, it seems that hesperidin could suppress the progression of the cellular model of PD via acting on intracellular calcium homeostasis. Further studies are needed to confirm the potential benefits of preventive and therapeutic effects of stabilizing cellular calcium homeostasis in neurodegenerative disease.

Effects of 660- and 980-nm low-level laser therapy on neuropathic pain relief following chronic constriction injury in rat sciatic nerve.

Neuropathic pain (NP) is one of the most suffered conditions in medical disciplines. The role of reactive oxygen species (ROS) and oxidative stress in the induction of NP was studied by many researchers. Neuropathies lead to medical, social, and economic isolation of the patient, so various therapies were used to treat or reduce it. During the recent years, low-level laser therapy (LLLT) has been used in certain areas of medicine and rehabilitation. Chronic constriction injury (CCI) is a well-known model for neuropathic pain studies. In order to find the effects of different wavelengths of LLLT on the injured sciatic nerve, the present research was done. Thirty Wistar adult male rats (230-320 g) were used in this study. The animals were randomly divided into three groups (n = 10). To induce neuropathic pain for the sciatic nerve, the CCI technique was used. Low-level laser of 660 and 980 nm was used for two consecutive weeks. Thermal and mechanical hyperalgesia was done before and after surgery on days 7 and 14, respectively. Paw withdrawal thresholds were also evaluated. CCI decreased the pain threshold, whereas both wavelengths of LLLT for 2 weeks increased mechanical and thermal threshold significantly. A comparison of the mechanical and thermal threshold showed a significant difference between the therapeutic effects of the two groups that received LLLT. Based on our findings, the laser with a 660-nm wavelength had better therapeutic effects than the laser with a 980-nm wavelength, so the former one may be used for clinical application in neuropathic cases; however, it needs more future studies.

Regulation of luteinizing hormone receptor in hippocampal neurons following different long-lasting treatments of castrated adult rats.

The aim of this study was to investigate the effects of different Luteinizing hormone (LH) and steroid hormones levels on LH receptor (LHR) expression in the hippocampal cells. Rats (24 males and 24 females) were assigned to four groups: one control and three experimental [gonadectomy (GDX), gonadectomy + gonadotropin releasing hormone analogue (GDX+GnRHa) and GDX+GnRHa+estradiol (E2) or testosterone (T)] independently for each gender. All experimental rats were gonadectomized; then GnRHa was administrated to GDX+GnRHa group, and GnRHa plus steroid hormone to GDX+GnRHa+E2 or T group in both genders for four-month. LHR mRNA expression and its protein level in hippocampal cells were measured using QRT-PCR and Western blotting. Quantification of mRNA revealed a decrease in LHR transcripts level in GDX+GnRHa group of females. A significant change was observed between GDX groups and GDX+GnRHa+E2 or T versus GDX+GnRHa group in females. High levels of LH decreased significantly the immature isoform of LHR in GDX group compared to control group in both genders, but low LH concentrations in GDX+GnRHa group induced immature LHR isoform production only in females. Therefore increased LH concentration induces production of incomplete LHR transcripts in hippocampal cells and decreases immature LHR at the protein level. This implies that LH decreases the efficiency of translation through either producing non-functional LHR molecules or preventing their translation.

Immune and nervous systems share molecular and functional similarities: memory storage mechanism.

One of the most complex and important features of both the nervous and immune systems is their data storage and retrieval capability. Both systems encounter a common and complex challenge on how to overcome the cumbersome task of data management. Because each neuron makes many synapses with other neurons, they are capable of receiving data from thousands of synaptic connections. The immune system B and T cells have to deal with a similar level of complexity because of their unlimited task of recognizing foreign antigens. As for the complexity of memory storage, it has been proposed that both systems may share a common set of molecular mechanisms. Here, we review the molecular bases of memory storage in neurons and immune cells based on recent studies and findings. The expression of certain molecules and mechanisms shared between the two systems, including cytokine networks, and cell surface receptors, are reviewed. Intracellular signaling similarities and certain mechanisms such as diversity, memory storage, and their related molecular properties are briefly discussed. Moreover, two similar genetic mechanisms used by both systems is discussed, putting forward the idea that DNA recombination may be an underlying mechanism involved in CNS memory storage.