Objective: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. The autoimmune pathology and long-term inflammation lead to substantial demyelination. These events lead to a substantial loss of oligodendrocytes (OLs), which in a longer period, results in axonal loss and long-term disabilities. Neural cells protection approaches decelerate or inhibit the disease progress to avoid further disability. Previous studies showed that metformin has beneficial effects against neurodegenerative conditions. In this study, we examined possible protective effects of metformin on toxin-induced myelin destruction in adult mice brains.Materials and Methods: In this experimental study, lysophosphatidylcholine (LPC) was used to i

Early life stress can serve as one of the principle sources leading to individual differences in confronting challenges throughout the lifetime. Maternal deprivation (MD), a model of early life stress, can cause persistent alterations in brain function, and it may constitute a risk factor for later incidence of drug addiction. It is becoming more apparent that early life MD predisposes opiate abuse in adulthood. Although several behavioral and molecular studies have addressed this issue, changes in electrophysiological features of the neurons are yet to be understood. The lateral paragigantocellularis (LPGi) nucleus, which participates in the mediation of opiate dependence and withdrawal, may be susceptible to modifications following MD. Th

Chronic pain is recognized as an important problem in communities. The Locus coeruleus (LC) with extensive ascending and descending projections has a critical role in modulating pain. Some studies indicate how the locus coeruleus-noradrenaline system can remain more active after nociceptive stimulation. In the present study, we examined whether formalin-induced inflammatory pain may affect the electrophysiological properties of LC neurons after 24 hours. Inflammatory pain was induced by a subcutaneous injection of 2% formalin (10 ?l) into the hind paw of 2-3 week-old male Wistar rats. After 24 hours, horizontal slices of brain stem containing the locus coeruleus were prepared and whole-cell patch-clamp recordings were carried out on L

Herein field recordings were utilized to test the effects of a transient period of pentylenetetrazol (PTZ) treatment on theta-burst long-term potentiation (LTP) at the Schaffer collateral-CA1 synapses as well as RT-PCR was used to investigate the effects of the combination of the pharmacological treatment and the theta-burst LTP induction on the expression of NMDA subunit mRNA in hippocampal slices. The slope of field excitatory postsynaptic potential (fEPSP) was unaffected while the population spike amplitude and area were increased by a transient period of PTZ treatment (3?mM, 10?min). After a theta burst, a brief PTZ exposure can lead to an enhancement of LTP as documented by fEPSP recording. The effect can be blocked by a s

Noradrenergic neurons of the locus coeruleus (LC) receive projection from hypothalamus orexinergic neurons and express orexin 1 receptor (Orx1). Orx in the locus coeruleus nucleus is involved in the development of morphine dependence. The downstream signaling of Orx contribution to the development of morphine dependence in LC neurons of morphine-dependent rats was studied. Therefore, we evaluated cyclic adenosine monophosphate (cAMP), cAMP response element-binding protein (CREB) and phospholipase Cβ3 (PLCβ3) levels by the application of immunohistochemistry. Results showed that cAMP, CREB and PLCβ3 levels were suppressed by the application of SB-334867 (as a selective Orx1 antagonist) in morphine-dependent rats. Our results unraveled tha

Despite years of research on pain comorbidity with affective disorders and cognitive deficits, it is still unclear how deficit in attention co-occurs with chronic pain. It is likely that altered neuroplasticity and or dysregulated neurotransmitters induced by chronic pain, at which pain and cognitive processing systems overlap, may have a negative effect on cognitive processing such as attention. One of the main common networks involved in attentional and pain processing is the noradrenergic system originating from the locus coeruleus (LC). We hypothesized that heightened noradrenaline release from LC induced by chronic pain could cause a deficit in visual attention. For this purpose, performance on the 5-choice serial reaction time test (5

Orexin neuropeptides are involved in opiate-induced physical dependence and expression of withdrawal signs following drug abstinence. Orexin type-1 receptors (OXR1) are expressed throughout the rostroventrolateral medulla (RVLM), particularly in the lateral paragigantocellularis (LPGi) nucleus. The present study examined whether blocking OXR1 in LPGi region could affect the development of morphine dependence and so behavioral manifestations induced by morphine withdrawal in rats.Male Wistar rats weighing 250-300 g were used. In order to induce drug dependence, morphine was injected subcutaneously (s.c.) (6, 16, 26, 36, 46, 56, and 66 mg/kg, 2 ml/kg) at an interval of 24 hours for 7 days. Animals were divided into two experimental gr

Early life aversive experiences can trigger persistent deficits in neuronal signaling within the mesolimbic pathway, most notably in the dopamine (DA) neurons of the ventral tegmental area (VTA). The identity of such cellular mechanisms currently appears as an important issue. To address this concern, we investigated whether early life maternal deprivation (MD) would affect the electrical activity of VTA DA neurons, via in vivo extracellular single-unit recording. Male Wistar rats were deprived of their dams for 3 h per day from postnatal days (PND) 1–14. Thereafter, the adult animals (PND 70–80) were tested for the discharge activity of putative VTA DA neurons. The VTA DA neurons displayed a decrease in firing rate and an increase in t

Pregnancy, as one of the crucial periods in the mother and fetus life, is extremely vulnerable to impairments such as drugs abuse. Every year, a large number of drug-addicted newborns are born due to mother's addiction. Drug abuse during pregnancy leads to appearance of several negative consequences for baby, such as an increased risk of preterm birth and congenital deficits. On the other hand, it affects the cognitive development of children like learning and memory, attention, language, problem solving skills and execuative functions by causing impairments in the central nervous system learning, memory and attention of the fetus and it also leads to cognitive and behavioral disorders such as depression, hyperactivity and anxiety. Opioids