effect of methylprednisolone on spatial learning and memory in adult male rats using an experimental model of Alzheimer's disease

The methylprednisolone [MP] is a synthetic glucocorticoid steroid initiallydeveloped for its enhanced anti-inflammatory activity. The present study aimed to examinethe effect of MP on the spatial learning and memory in an experimental model ofAlzheimer's disease in rats. Male rats were allocated into five groups: control group; lesiongroup which received electrically-induced lesion [0.5 mA, 3s] in the nucleus basalismagnocellularis [NBM] to create Alzheimer's model; sham group [the electrode wasimpaled into the NBM with no lesion]; MP group [lesion+30 mg/kg MP] and saline group [lesion NBM + 0.2 mL saline]. After one week, the rats were trained to perform the Y-mazetask for five days. The animals were tested for spatial memory one month later. Results showed that the bilateral lesion of NBM impaired the .spatial learningcompared to the control group [P=0.01]. The administration of MP significantly improved spatial learning of rats with the Alzheimer's disease [P<0.001]. Moreover, no effect onspatial learning was seen in the sham group compared with the lesion group. No significantdifference was observed between the results in the 5th day of training and the memory testafter one month. Administration of MP can be an effective treatment for the Alzheimer'sdisease

effect of systemic administration of dbcamp on neural stem cells migration in eae model of multiple sclerosis

Background and Purpose: Novel strategies of MS try to stimulate endogenous neural stem cells for demyelination repair. Increased levels of cAMP potentiate the repair mechanisms in CNS by activating PKA or independently. In the present study, we investigated the effect of dbcAMP on neural stem cells migration in experimental autoimmune encephalomyelitis [EAE] model of MS

Methods and Materials: Mice were immunized with 300 microg MOG peptide emulsified in complete Freund's adjuvant [CFA] and pertussis toxin [PT]. Control mice received CFA and PT. Groups of EAE- mice received i.p. injections of dbcAMP 10mg/kg from day 9-14 or 9-21. Animals were observed daily for neurological deficit. Nestin expression was used as a marker to detect neural stem cells. The number of Nestin+ cells in SVZ and olfactory bulb [OB] was evaluated using immunohistochemical staining. GraphPad Prism Version 5 was used for analyzing the data. For the clinical signs of EAE, the differences between the same days were compared by unpaired t-test. For the number of Nestin+ cells, the statistical differences between the groups were determined by one-way ANOVA and Tukey post-test

Results: EAE induction caused clinical signs and paralysis of tail and hind limbs. dbcAMP significantly reduced the incidence and severity of EAE in mice immunized with MOG. Maximum of scores reached 0.66 +/- 0.13 for dbcAMP treated mice [2.5 +/- 0.2 for EAE mice] on 21 dpi [day post inductin]. EAE induction did not change number of nestin+ cells in SVZ but it increased it in OB. With developing of scores on 21dpi, the number of cells decreased [5.66 +/- 1.20]. dbcAMP injection from 9-21 dpi increased these cells in SVZ. With developing of EAE scores on 21 dpi, the number of these cells in OB increased [19.5 +/- 2.04] and has significant differences with the control group. The treatment of EAE induced mice with dbcAMP from 9-21 dpi was assosiated with a significant elevation of Nestin+ cells in OB [40 +/- 2.73] [P<0.001].

Conclusion: Treatment with the dbcAMP and PKA activation effectively control the EAE signs via increasing the number of neural stem cells and inducing their migration from SVZ to OB and demyelinated lesions, and decrease the symptoms

[Effects of corticosterone injections after training and memory reactivation on recall of fear memory in rats]

Recent evidence indicated that when a stabilized memory is recalled or reactivated, it again becomes labile and initiates a time-dependent process referred to "reconsolidation". Considering the documented role of stress hormones on emotional memory, the purpose of this study was to compare the effects of glucocorticoids on consolidation and reconsolidation of a fear conditioning memory. Adult male Wistar rats were trained in fear conditioning system. In experiment 1, rats were placed into context and after 180 s were given two 2 s, 0.4 mA shocks with an interval of 120 s. Twenty seconds after the final shock, rats removed from the context box and were injected with different doses of corticosterone or vehicle. In reconsolidation experiments, rats received 2 s, 0.4 mA shocks with an interval of 120 s [moderate memory] or given eight 2 s, 1.5 mA shocks with an interval of 62 s [strong memory]. Thirty seconds after the final shock, rats removed from the context box. For reactivation, 24 h later rats were returned to the chamber for 90s. Immediately after reactivation, rats were injected with different doses of corticosterone or vehicle. Twenty-four hours after training or memory reactivation, rats were returned to the context box for 5 min. Seconds of freezing [defined as the absence of all visible movement oxcept respiration] during the retrieval testing were scored for each rat. The findings indicated that injections of corticosterone after training enhanced memory consolidation at dose of 3 mg/kg. Injections of the drug after memory reactivation did not change recall of moderate memory, but impaired recall of strong memory at dose of 3 mg/kg. The data indicate that glucocorticoids have opposite effects on consolidation and reconsolidation of contextual fear conditioning memory. Further studies are needed to determine the underlying mechanisms

Responsiveness of PGi neurons to the noxious stimulus in capsaicin treated morphine dependent rats

Nucleus reticularis paragigantocellularis [PGi] is one of the major components of the rostral ventromedial medulla [RVM], which is involved in nociceptive processing and pain modulation. The aim of this study was to examine the effect of C fiber destruction on responsiveness of nucleus reticularis paragigantocellularis [PGi] to formalin, as a noxious stimulus, in normal and morphine dependent rats. C-fiber destruction was induced by neonatal capsaicin [CAP] treatment [50mg/Kg, s.c.], in the second postnatal day. Extracellular single unit recording was used in control, capsaicin treated and morphine dependent, urethane [1.2-1.5g/Kg] anesthetized rats. After baseline recording [40 min], 100micro l formalin [5%] was injected into the controlateral hind paw and recording was continued in the PGi, for 60 min after noxious stimulus. In control rats three types of neurons were detected, which were categorized as, increased [38.45%], decreased [23.1%] and neutral neurons [38.45%]. In CAP treated rats the 3 types of neurons were observed, too. The duration of response [Baseline +/- 2SD], in CAP treated rats was significantly shorter than that of controls. All recorded neurons in morphine dependent rats were neutral, but 30% of recorded neurons in CAP treated morphine dependent rats showed short increase in firing rate. It was concluded that C-fiber destruction may just reduce the time course of changes in firing rate in response to peripheral noxious stimulus, while chronic morphine exposure may suppress the neuronal responsiveness, totally

effect of morphine injection in the priaqueductal gray matter on the neuronal responsiveness of nucleus reticularis paragigantocellularis to formalin

Nucleus reticularis paragigantocellularis [PGi] has a very effective role in the supraspinal pain modulation. PGi as a rostroventromedial medulla [RVM] structure receives a major input from periaqueductal gray matter [PAG].Formalin as a peripheral noxious stimulus has biphasic nociception and behavioural manifestations. To assess morphine injection in the priaqueductal gray matter[PAG] on the neuronal responsiveness of nucleus reticularis paragigantocellularis [PGi] to formalin. The experimental subjects were male NMRI rats. Diluted formulin [2.5%] as a chemical noxious stimulus and morphine as an analgesic drug were used. Using single unit recording [an extracelluar recording electrophysiologic method] the research was done. Findings indicate that the responses of the PGi inhibitory neurons evoked by formalin were disinhibited by morphine microinjection in the FAG. In the excitatory neurons, morphine decreased the firing rate to the baseline activity. PGi inhibitory neurons are affected by the PAG's GABAergic interneurons. Morphine blocks GABA released from these intenneurons and results to off- cell disinhibition. On- cells suppressions are probably related to morphine effects directly

Effects of formalin as a peripheral noxious stimulus on the nucleus reticularis paragigantocellularis neurons of ansethetized rats

In the present study, the effects of formalin as a peripheral noxious stimulus on spontaneously active units of the nucleus reticularis paragigantocellularis [PGi], a narrow region of the ventral pontine reticular formation, was examined in urethane anesthetized rats. Spontaneous discharge of the PGi neurons was variable, ranging from I to 37 spikes per second. Formalin as a chemical irritant and prolonged noxious stimulus induced changes in the firing of spontaneously active PGi neurons. There were three neuronal subpopulations in the PGi that responded to formalin: excited [19.35%], inhibited [45.16%] and unchanged [35.48%]. Thus we suggest that PGi neurons may be involved in the processing of information related to formalin as a chemical irritant

Involvement of supraspinal alpha-adrenergic receptors in tonic pain

The involvement of supraspinal alpha-adrenergic receptors in tonic pain was assessed in formalin-induced pain in rats. The alpha [2] adrenoceptor agonist clonidine, along with yohimbine and prazosin, Alpha2 and Alpha1 receptor antagonists, were introduced intracerebroventrically [icv] and/or systemically in different doses. The data show that 1] clonidine exerts an alpha adrenergic analgesic effect, in addition to its known alpha [2] role in this kind of pain, 2] icv yohimbine did not change the rat's nociception, and 3] icv prazocin also failed to alleviate the animal's nociception although both the latter drugs show analgesic activity in the formalin test when injected systemically. It can be concluded that Alpha1 receptors contribute significantly to adrenergic analgesia in the formalin test in supraspinal structures, by undefined nature and site[s]

effect of clonidine on chorda tympani neural response to salt and sweet tastes in the rat

Two commonly used tastants, sucrose and sodium chloride, were applied to the tongue surface of rats while recording was made from their gustatory peripheral nerve, chorda tympani [CT]. This multiple unit recording was performed in the presence of different doses of clonidine, an antihypertensive drug. Clonidine, in low doses [0.15, 0.25 mg/kg, intraperitoneally] caused a significant decrease in the relative integrated neural responses of the rats' CT to NaCl [0.1 M] and sucrose [0.5 M] as compared to the reference solution [NH4Cl] [p<0.05]. In these doses clonidine did not act selectively in response to these special tastants, but in higher doses [0.5 mg/kg], it attenuated the nerve response to sucrose, while no effect was elicited on the response to NaCl

effect of locus coeruleus lesioning on tonic and phasic pain

Bulbospinal noradrenergic pathways are shown to have an important role in descending inhibition of pain sensation. Locus ceruleus [LC], as a rich noradrenergic nucleus in the brain stem which has projections into the dorsal horn of the spinal cord, was evaluated for antinociceptive activity by using tonic and phasic pain models in the rat. LC-lesioned rats demonstrated moderate increase in both phases of the formalin test, but did not show any effect to thermal noxious stimuli, applied in the tail-flick test. These results indicate the relative involvement of LC in inhibition of tonic, but not phasic, pain