Activation of androgen receptors alters hippocampal synaptic plasticity and memory retention through modulation of L-type calcium channels.

AIMS: It has been revealed that membrane androgen receptor activation modulates avoidance memory and synaptic plasticity. In a previous study, we showed that Calcineurin, a calcium dependent phosphatase, could be a potential mediator of these AR effects. Also, it is reported that AR activation leads to L-type calcium channel activation. The aim of the current study is to test whether L-type calcium channels are downstream of AR and whether this signal pathway mediates the impairment effect of androgenic steroids on passive avoidance memory and synaptic plasticity. MATERIALS AND METHODS: We measured the effect of Nandrolone Decanoate (AR agonist), AR antagonist (Nilutamide) plus ND or L-type calcium channel inhibitor (Nifedipine) plus ND on passive avoidance performance of adolescent male rats. For extracellular field potential recordings hippocampal slices were perfused with ND, Nilutamide-ND or Nifedipine-ND. KEY FINDINGS: Our results clarified that AR activation by ND could impair avoidance behavior as step through latency decreased in ND-treated group while application of both Nilutamide and Nifedipine reestablished normal avoidance behavior. Also, LTP induction in the CA1 area of hippocampus was diminished by ND perfusion and both AR antagonist and L-type calcium channel inhibitor application lead to normal LTP. These findings support our hypothesis that activation of L-type calcium channels are involved in ARs mechanism effects on both avoidance behavior and hippocampal synaptic plasticity. SIGNIFICANCE: Understanding the biological effects of AR agonists on cognitive processes and its cellular mechanism may be a new/supplementary way to treating fear-related disorders.

Effects of Memantine on the Spontaneous Firing Frequency of Hippocampal CA1 Pyramidal Neurons in Intact and Alzheimer Rat Model: An Electrophysiological Study.

Introduction: Memantine (MEM) is a noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist clinically used for the treatment of Alzheimer disease (AD) in mild to severe conditions. The present study was conducted to investigate the effects of memantine on the spontaneous firing frequency of CA1 pyramidal neurons in rats caused by an electrical lesion of Nucleus Basalis Magnocellularis (NBM). Then, this model of AD rats was compared with the intact adult male rats. Methods: In this study, adult male rats were divided into two groups. Group I (lesion of NBM, n=53) includes the following subgroups: lesion+saline, sham+saline, lesion+MEM 5 mg/kg, lesion+MEM 10 mg/kg, and lesion+MEM 20mg/kg. Group II (intact, n=48) includes the following subgroups: intact+saline, intact+MEM 3mg/kg, intact+MEM 5mg/kg, and intact+MEM 10mg/kg. Extracellular single-unit recording (15 min baseline+105 min after MEM or saline) was performed under urethane-anesthetized rats. Results: The results showed that the mean frequency of CA1 pyramidal neurons after saline in the lesion+saline (P<0.001) group significantly decreases compared with the intact+saline and sham+saline groups. In addition, after saline and memantine, the mean frequency of CA1 pyramidal neurons in the lesion+MEM 10 mg/kg (P<0.01) and lesion+MEM 20 mg/kg (P<0.001) groups significantly increased compared with the lesion+saline group. Also, the mean frequencies of CA1 pyramidal neurons in the intact+MEM 10 mg/kg (P<0.001) group significantly decreased compared with the intact+saline group. Conclusion: Results showed that memantine increases the electrical activity of CA1 pyramidal neurons in a rat model of AD. Furthermore, in the intact adult male rats, the low-dose memantine, contrary to high dose, does not decrease the electrical activity of CA1 pyramidal neurons.

The Therapeutic Effects of Low-Frequency Electrical Stimulations Adjunct to Sodium Valproate on Seizure and Behaviors.

INTRODUCTION: Consuming antidepressant medications induce several problems leading to the need for alternative agents for emotional disturbances. Antidepressant medications increase the seizure risk; thus, alternative treatments, like Antiepileptic Drugs (AED), might be useful for patients with epilepsy comorbid with a psychiatric disorder. The present study evaluated the behavioral effects of sodium valproate, a none effective dose in seizure treatment [100 mg/kg; Intraperitoneal (IP)] along with the application of Low-Frequency Stimulations (LFS) during CA1 hippocampal kindling. METHODS: In total, 42 male rats were randomly divided into 6 groups, including control group with intact animals handled daily (I); sham group which was subjected to the surgical process, but received no real stimulation (II); saline-kindled Kindled group (S.kindled) which were stimulated daily with the following protocol: 3 strain of 50Hz monophasic pulses of 1ms duration applied 12 times a day with the threshold intensity at intervals of 10 minutes where saline was administrated 15 min before kindling stimulations (III); saline-kindled-LFS group (K4LFS) in which saline was injected 15 min before kindling stimulations and LFS was applied daily after the termination of kindling stimulation (IV); drug-kindle group (Drug100.kindled) that underwent rapid kindling procedure daily where sodium valproate (100 mg/kg) was administrated 15 min before kindling stimulations(V), and drug-kindled-LFS (Drug100.kindled.4LFS) group in which drug and LFS were administrated respectively before and after kindling stimulations (VI). The behavioral tests were assessed using elevated plus maze, open field, and forced swim tests. RESULTS: The combination of sodium valproate (100 mg/kg) and LFS significantly decreased cumulative seizure severity compared with the kindle group. Thus, it provided a strong seizure suppressing effect. Additionally, sodium valproate and LFS increased the percentage of Open Arms (OAs) entries and the OAs exploration; they also decreased jumping from elevated plus maze test and rearing in open field test. Furthermore, there was no significant change in the OAs entries and OAs exploration percentages, jumping from apparatus, and rearing in open field in Drug100. Kindled, K4LFS, and Drug100.kindled.LFS groups, compared with the sham group. There was no significant difference in the latency to first immobility and the duration of immobility in K4LFS groups compared with the S. kindled group. In the drug-kindled group, the latency to first immobility significantly increased, and the duration of immobility decreased, compared with the S. kindled group. Besides, the latency to first immobility significantly increased, and the duration of immobility decreased in drug-kindled-LFS, compared to S. kindled group; however, the latency to first immobility was not significantly changed, compared to drug-kindled groups. CONCLUSION: Sodium valproate and LFS can modulate the function of the brain regions involved in emotional processing in epilepsy, as well as anxiety- and depressive-like behaviors. Such a combination could also decrease emotional disturbances induced by the kindling process.

Interaction of Sodium Valproate With Low-Frequency Electrical Stimulation During Kindlingn.

INTRODUCTION: The interaction between antiepileptic drugs and brain electrical stimulation is a potential therapy to control seizures in patients with pharmacoresistance to drugs. So, the present study aimed to design to determine the effect of a subeffective dose of sodium valproate combined with low-frequency electrical stimulation during kindling. METHODS: One tripolar electrode was implanted stereotactically in the CA1 hippocampus of male Wistar rats. One week after surgery, the rats were kindled by electrical stimulation of hippocampus in a rapid manner (12 stimulations/day) for 6 days with sodium valproate alone or combined with low-frequency electrical stimulation (four packages contained 200 monophasic square wave pulses of 0.1-ms duration at 1 Hz, immediately after kindling stimulations). The duration of afterdischarge, maximum latency to stages 4 and 5, and the maximum duration of these stages were recorded by electromadule during kindling. RESULTS: Application of sodium valproate with low-frequency electrical stimulation caused a reduction in cumulative afterdischarge duration. The maximum latency to the onset of stage 5 seizure increased after sodium valproate application alone, without having a significant effect on the fourth stage. Our findings showed reductions in the seizures duration and increasing in the latency times of both stages after the application of sodium valproate with low-frequency electrical stimulation. CONCLUSION: It seems that usage of sodium valproate with low-frequency electrical stimulation during kindling was more effective to suppress the epileptic activity than its administration alone and may have a critical role on the antiepileptic effects of sodium valproate.

Nandrolone improve synaptic plasticity at the hippocampus CA1 area and spatial localization in the Morris water maze of male adolescent rats.

Nandrolone is the most popular compound that are mainly abused. Experimental studies have reported that administration of nandrolone affects cognitive performance. So, the aim of this study is to evaluate the effect of nandrolone on spatial localization and synaptic plasticity of male adolescent rats. Experimantal groups received DMSO and nandrolone (10, 30 and 60 µg, i.c.v.). Another aim is to evaluate the role of castration on spatial learning and memory changes induced by nandrolone. Therefore, the rats of fifth and sixth groups were castrated and received DMSO or nandrolone. Analysis showed that escape latency and traveled distance in the group which received nandrolone (60 µg) were significantly lower than control group. Also, the escape latency and traveled distance in the group of castration which received nandrolone was significantly higher than nandrolone treated group. The results of field potential recording showed that fEPSP-LTP in nandrolone-treated group was higher than DMSO-treated group. The magnitude of fEPSP-LTP in the group of castration which received nandrolone was significantly lower than nandrolone-treated group. The results demonstrated that nandrolone improved spatial learning, but castration could abolished nandrolone-induced spatial learning improvement. These results indicating that at least some effect of nandrolone on learning induced through changes in gonadal function.

Calcineurin is involved in retrieval of passive avoidance memory and synaptic plasticity impairment induced by Nandrolone administration in adolescent male rats.

In spite of evidence about negative effects of Nandrolone Decanoate (ND) on cognitive and memory performance, the underlying mechanisms are complex and have remained unclear. This research examines the role of Calcineurin in synaptic plasticity and memory storage impairment in ND administrated adolescent male rats. For behavioral study by passive avoidance learning and memory (PAL), adolescent male rats were treated with ND or ND plus selective Calcineurin antagonist (Tacrolimus), before retention test. ND significantly decreased the retrieval of PAL, whereas Tacrolimus plus ND had no significant effect on PAL. For electrophysiological study hippocampal slices were perfused by ND or ND plus Tacrolimus. The magnitude of fEPSP-LTP of ND perfused slices was less than the control and a reduction of fEPSP-PS (E-S) coupling was observed, while pre-administration of Tacrolimus abolished the ND impairment effect on fEPSP-LTP and E-S coupling. This study showed that ND may induce impairing effects on hippocampal area CA1 activity and plasticity and PAL memory storage through changes in the function of the Calcineurin.

Effects of Donepezil Hydrochloride on Neuronal Response of Pyramidal Neurons of the CA1 Hippocampus in Rat Model of Alzheimer's Disease.

INTRODUCTION: Donepezil (DON), an Acetylcholinesterase Inhibitor (AChEI), is widely used in the treatment of Alzheimer's Disease (AD). The current study aimed at evaluating the effect of donepezil hydrochloride on pyramidal neuron response in CA1 region of a rat model of AD. METHODS: In the current experimental study, adult male Wistar rats were randomly divided into four groups: Nucleus Basalis Magnocellularis (NBM) lesion (the lesions were induced by an electrical method of 0.5 m A, for 3 s in NBM) and three donepezil groups (lesions plus 5, 10, and 15 mg/kg donepezil intraperitoneal injection). Neuronal spontaneous activity to injection of the donepezil and saline were recorded in CA1 region of hippocampal. RESULTS: The obtained results showed that IntraPeritoneal (IP) injection of donepezil (10 and 15 mg/kg) increased neuronal spontaneous activity in the rat model of AD. CONCLUSION: The current study results suggested that acute IP injection of donepezil increased neuronal response in CA1 region of hippocampal in a rat model of AD.

Nandrolone administration abolishes hippocampal fEPSP-PS potentiation and passive avoidance learning of adolescent male rats.

Despite the chronic effects of nandrolone decanoate (ND), the acute effects of ND on passive avoidance learning (PAL) and memory and its mechanism have not been investigated. This research examines the acute effect of ND on PAL, CA1 synaptic plasticity, testosterone and corticosterone serum levels, and the role of androgenic receptors (ARs). Adolescent male rats were treated with ND, 30 min before training and retention and after training test. AR antagonist was applied 15 min before ND. Hippocampal slices were perfused by ND. ND administration had an inverted U-shape effect on acquisition of PAL and on testosterone and corticosterone serum levels. The consolidation was only affected by high dose of ND. ND significantly decreased the retention of PAL across all doses. The magnitude of field excitatory postsynaptic potential long term potentiation was lower than that of control slices. In addition, an attenuation of field excitatory postsynaptic potential population spike coupling was also observed. Nilutamide could nullify the ND impairment effect. We concluded although a single dose of ND could affect all stages of PAL, its effects were more potent on retrieval, possibly arising from the acute effect of ND on the alterations of CA1 synaptic plasticity. In addition, ND may induce its effects directly through ARs and indirectly through plasma testosterone and corticosterone.

Quantitative Analysis of the Antiepileptogenic Effects of Low Frequency Stimulation Applied Prior or After Kindling Stimulation in Rats.

Background and Objective: Developing quantitative measures based on spectral analysis of electroencephalograph (EEG) recordings of neural activities plays an important role in developing efficient treatments for epilepsy. Such biomarkers can be used for developing open or closed loop approaches for seizure prediction or prevention. This study aims to quantitatively evaluate antiepileptogenic effects of low frequency stimulation (LFS) applied immediately before or after kindling stimulations using spectral power analysis of extracellular EEG in rat. Methods: Nineteen adult rats were used: seven for kindle, six for LFS+Kindle (LFSK) and six for Kindle+LFS (KLFS). Four packages of LFS (1Hz) were applied immediately before or after rapid kindling stimulations. The power spectral densities of afterdischarge (AD) sections of EEG corresponding to different stages of kindling for delta (0-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-28 Hz), gamma (28-40 Hz) sub-bands, and theta/alpha ratio were comparatively investigated. Moreover, correlation between AD duration (ADD) and its different frequency components was calculated. Results: Both LFSK and KLFS significantly increased delta and reduced beta and gamma oscillations, compared with kindle group. However, just the reduction in LFSK group was significant. Both protocols increased theta/alpha ratio, but just LFSK showed significant increase (p < 0.05). Although LFSK enhanced theta/alpha ratio more than KLFS, the difference was not statistically significant. Furthermore, strong correlation between each frequency sub band and ADD was not observed in kindle and LFS treated groups (both LFSK and KLFS). Conclusion: Although behavioral assessments showed relatively the same level of antiepileptogenic effects for KLFS and LFSK, quantitative assessments showed more significant differences in the quantitative measures between the two protocols. Developing more quantitative EEG based measures correlated with LFS-induced effects can facilitate developing open or closed loop seizure prevention modalities.

Improving cognitive task in kindled rats by using low frequency stimulation during epileptogenesis.

Numerous studies indicate that one of the bad effects of epilepsy is cognitive impairment. In this study we focused on the effect of LFS as a potential anticonvulsant agent, during epileptogenesis on cognitive impairments induced by amygdala kindling in rat. Twenty-one adult rats were divided into 3 groups including control (n = 7), kindled (n = 7), and Kindled+LFS (KLFS) (n = 7). Animals in the kindled group received kindling stimulation in a rapid kindling manner (a 3 s train of 50 Hz monophasic pulses of 1 ms duration, 12 times a day) in amygdala whereas control animals had no stimulation. Four packages of LFS (each package consisting of 200 monophasic square pulses, 0.1 ms pulse duration at 1 Hz) were applied daily after termination of kindling stimulation in KLFS group. Spatial memory of all animals was tested using radial arm maze after termination of stimulation on acquisition trial days and 14 days after the final acquisition trial test. Epileptogenesis process significantly increased working and reference memory error compared to control groups whereas application of LFS immediately after kindling stimulation prevented this impairment in 8 arm radial maze and there was no significant difference between KLS and control groups. Our results indicated that application of LFS during kindling acquisition suppresses memory impairment in epileptogenesis by kindling stimulation.

Transplanted neural-like cells improve memory and Alzheimer-like pathology in a rat model.

BACKGROUND AIMS: Degeneration of the central nerve system, particularly in Alzheimer's disease, is a burden on society, and despite years of research, there is no effective treatment. Cell therapy appears to be an option that is of growing interest in neural studies. The main aim of this study was to investigate the histological and physiological effects of transplantation the neuron-like cell (NLC)-derived mouse embryonic stem cells (mESCs) on the repair of brain lesions in an Alzheimer's animal model (AM) in rats. METHODS: Behavioral experiments were conducted in the light hours in a Y-shaped maze device. Animals were randomly divided into five groups, with seven rats per group. The nucleus basalis of Meynert (NBM) was destroyed bilaterally with an electrical lesion (0.5 mA for 3 s). One week after the bilateral lesion of the NBM, the differentiated NLCs (0.1 mL) were injected with stereotaxic surgery using a Hamilton syringe at NBM coordinates, and behavioral and histological tests were performed by the Y-maze task and hematoxylin and eosin staining after five weeks of the lesion. Also, differentiated cells detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis and fluorescent immunostaining. RESULTS: The expression of neuronal markers including Nestin, Map2, NF-H, Tuj-1, GFAP and Olig-2 was surveyed by using the immunocytochemistry and qRT-PCR methods, and the results confirmed that the genes in question were expressed significantly more compared than the control sample. Five weeks after the cell transplantation in the AM, morphological and physiological investigation during the determination period confirmed improved disease state in the tested models. CONCLUSIONS: It should be noted that by improving the neuronal connectivity in AM rat brains, the transplanted NLCs rescue Alzheimer's cognition. This research has presented some preclinical evidence that showed NLCs transplantation can be used for AM treatment.

Quantitative assessments of extracellular EEG to classify specific features of main phases of seizure acquisition based on kindling model in Rat.

OBJECTIVE: Quantitative assessments of extracellular EEG to identify specific features of three main phases of seizure acquisition based on kindling model in Rat. METHODS: Male rats were divided into 2 groups including kindled (n=10) and sham (n=7) and respectively underwent an amygdala rapid kindling and placebo kindling. EEG signals in stages 1-2 (initial seizure stages (ISSs)), 3 (localized seizure stage (LSS)), and 4-5 generalized seizure stages (GSSs) were divided into 5 bands: delta (0-4Hz), theta (4-8Hz), alpha (8-12Hz), beta (12-28Hz), and gamma (28-40Hz). Spectral power of the sub bands and the ratios of theta/alpha and delta/beta were compared in the three phases and between the sham and kindling groups. RESULTS: Beta power significantly increased during kindling acquisition, though it was significantly lower than sham. Delta oscillation in ISSs was higher than LSS and GSSs, but the difference was significant only with LSS. Moreover, delta power was higher in all stages of kindling than sham. Gamma power in all stages of kindling was significantly lower than sham. Alpha power was significantly reduced in ISSs, compared with sham, but gradually increased during epileptogenesis. Theta/alpha and delta/beta increased in all stages, compared with sham (p<0.05). Theta/alpha significantly decreased in LSS and GSSs, compared with ISSs (p<0.05). Delta/beta decreased during kindling, but it was significantly different only between ISSs and LSS (P<0.05). CONCLUSION: Beta and alpha oscillations at ISSs significantly decreased, but gradually increased along with kindling progression. Furthermore, delta power significantly increased during kindling process.

Low Frequency Electrical Stimulation Either Prior to Or after Rapid Kindling Stimulation Inhibits the Kindling-Induced Epileptogenesis.

Objective. Studies are ongoing to find appropriate low frequency stimulation (LFS) protocol for treatment of epilepsy. The present study aimed at assessing the antiepileptogenesis effects of LFS with the same protocol applied either just before or immediately after kindling stimulations. Method. This experimental animal study was conducted on adult Wistar rats (200 ± 20 g) randomly divided into kindle (n = 7), LFS + Kindle (n = 6), and Kindle + LFS groups (n = 6). All animals underwent rapid kindling procedure and four packages of LFS (1 Hz) with 5 min interval were applied either immediately before (LFS-K) or after kindling stimulation (K-LFS). The after discharge duration (ADD), daily stages of kindling, and kindling seizure stage and number of stimulations required to reach each stage were compared between the three groups using two-way analysis of variance (ANOVA) followed by Tukey post hoc and one-way ANOVA, and Kruskal-Wallis test, respectively. Results. LFS in both protocols significantly decreased the ADD (p < 0.05) and daily seizure stages (p < 0.05) and increased the number of stimulations required to achieve stage 3 and stages 4 and 5 of kindling compared with the kindle group (stage 2: p > 0.05, stages 3 to 5: p < 0.05). Conclusion. Although LFS-K showed more inhibiting effect than K-LFS, the difference was not statistically significant.

Classifying amygdala kindling stages using quantitative assessments of extracellular recording of EEG in rats.

PURPOSE: Determining different seizure stage specific features in a kindling model is a crucial step in developing efficient objective techniques for early prediction and treatment of seizures. This study identified and categorized kindling stages based on their electrophysiological features through processing extracellular field potentials of Amygdala rapid kindling. METHODS: Thirteen Wistar rats (200±10g) were divided into 2 groups including kindle (n=7) and sham (n=6) and respectively underwent an amygdala rapid kindling and placebo stimulation. EEG signals in each stage were classified into 7 bands: delta (0-4Hz), theta (4-8Hz), alpha (8-12Hz), low beta (12-16Hz), mid beta (16-20Hz), high beta (20-28Hz) and gamma (28-40Hz). Spectral power and power of sub bands of stage 3 (localized seizure stage (SS)) and stages 4 and 5 (generalized SSs) were compared between kindling and sham groups. RESULT: Spectral analyses showed larger spikes in delta and theta subbands in the stages of 3, 4, and 5 of kindling, compared with sham animals. Generalized SSs contained more spikes than the localized SS in the kindling. Kindling process was accompanied by reduction in high beta and gamma oscillations and increase in delta sub band power which were significant in the generalized SSs. The theta/alpha ratio in the localized SS was higher than the generalized SSs and sham group, but the difference with the sham group was statistically significant. CONCLUSION: Our results showed that reduced high beta and gamma and increased delta oscillations power are associated with behavioral seizure progression.

Involvement of l-arginine-nitric oxide pathway in anxiolytic-like effects of zinc chloride in rats.

PURPOSE: Zinc is crucial for normal development of the brain, and Zinc deficiency has been shown to associate with neurological disorders (e.g. anxiety) through interactions with several neurotransmitter systems such as nitric oxide (NO). In this regard, our study aimed to evaluate the possible involvement of l-arginine NO pathway on anxiolytic effects of zinc in adult male rats. METHODS: Zinc chloride at doses of 2.5 and 10mg/kg (intraperitoneal or ip) or saline (1ml/kg, ip) were injected 30min before the anxiety test. Zinc administrated rats (10mg/kg) were pre-treated with intra-CA1 microinjection of l-arginine in sub-effective dose of 1µg/rat (dorsal hippocampus, vehicle: saline1µl/rat). In addition, zinc chloride and NG-nitro-l-arginine methyl ester (l-NAME) were intraperitoneally co-administrated in sub-effective doses of 2.5mg/kg and 80mg/kg, respectively. The percentage of open arm time (OAT%), percentage of open arm entry (OAE%), as measures of anxiety, and total number of arm entries, as measures of locomotor activity, were recorded. RESULTS: Treatment with zinc (10mg/kg) markedly produced an increase in OAT% and OAE% in the Elevated plus maze test (EPM). A decrease of OAT% and OAE% was shown in groups which received zinc (10mg/kg) and l-arginine (1µg/rat) concomitantly as compared to the control group. Moreover, an increase of OAE% was revealed in the group exposed to Zinc (2.5mg/kg) and l-NAME (80mg/kg) co-administration. Although, Two-way ANOVA showed no significant differences of anxiety indices in rats received drug+zinc chloride in compare to the zinc pretreated with saline group. CONCLUSION: Anxiolytic- like effect of zinc reversed by nitric oxide precursor l-arginine. Additionally, the synergistic effects of l-NAME and ZnCl2 were shown in the EPM. Thus our findings suggest that at least in part the anxiolytic effects of zinc can be mediated through the nitric oxide system.

Long-term effects of maternal exposure to Di (2-ethylhexyl) Phthalate on sperm and testicular parameters in Wistar rats offspring.

BACKGROUND: Phthalate esters have been shown to cause reproductive toxicity in both developing and adult animals. OBJECTIVE: This study was designed to assess long-term effects of maternal exposure to Di (2-ethylhexyl) Phthalate (DEHP) on reproductive ability of both neonatal and adult male offspring. MATERIALS AND METHODS: 60 female rats randomly divided in four equal groups; vehicle control and three treatment groups that received 10, 100 and 500 mg/kg/day DEHP via gavage during gestation and lactation. At different ages after birth, the volumes of testes were measured by Cavellieri method, testes weights recorded and epididymal sperm samples were assessed for number and gross morphology of spermatozoa. Following tissue processing, seminiferous tubules diameter and germinal epithelium height evaluated with morphometric techniques. RESULTS: Mean testis weight decreased significantly (p<0.05) in 500 mg/kg/day dose group from 28 to 150 days after birth. Significant decreases were seen in total volumes of testis in 100 (p<0.05) and 500 (p<0.01) mg/kg/day doses groups until 150 days after birth. Seminiferous tubules diameter and germinal epithelium height decreased significantly in 100 (p<0.05) and 500 (p<0.01) mg/kg/day doses groups during postnatal development. Also, mean sperm density in 100 mg/kg/day (p<0.05) and 500 mg/kg/day (p<0.01) doses groups and percent of morphologically normal sperm in highest dose group (p<0.05) decreased significantly until 150 days after birth. CONCLUSION: Present study showed that maternal exposure to Di (2-ethylhexyl) Phthalate during gestation and lactation caused to permanent and dose-related reductions of sperm and testicular parameters in rats offspring.

Memory and motor coordination improvement by folic Acid supplementation in healthy adult male rats.

OBJECTIVES: Previous studies have shown that vitamin B as well as folate supplementation has been implicated in cognitive and neurodegenerative disorders including Alzheimer's and Parkinson's diseases. The aim of present study was to evaluate the effects of folic acid on passive avoidance task and motor coordination in healthy adult male rats. MATERIALS AND METHODS: Animals were randomly divided into five groups with 10 in each. 1) Sham treated (Veh); received same volume of normal saline as folate vehicle, 2-5) Test groups; each received a single dose of folate (5, 10 and 15 mg/ml/kg, IP daily for one week). At the end of the treatment with folic acid or vehicle, motor coordination in rotarod (after 24 hr) and passive avoidance memory in shuttle box (after 2 and 30 days) were evaluated, respectively. RESULTS: The results showed that folic acid (5, 10, and 15 mg/kg) increased short-term (P<0.05, P<0.001) memory while, long term memory affected significantly with doses 10 and 15 mg/kg (P<0.01, P<0.001). On the other hand, folic acid (5 and 10 mg/kg) had significant improving effect on motor coordination (P<0.001, P<0.01) but with 15 mg/kg dose didn't have any effect on motor coordination. CONCLUSION: Our results suggest that folic acid may improve both short- and long-term memories, dose dependently, although it affects motor balance at lower dose. The mechanism of folic acid effects on cognition and motor coordination is unknown and needs more investigations.

Long-term Developmental Effects of Lactational Exposure to Lead Acetate on Ovary in Offspring Wistar Rats.

BACKGROUND: During the last decades, environmental contamination by lead generated from human activities has become an evident concern. The present study assessed the long-term effects of neonatal exposure to different doses of lead acetate on the ovaries of offspring rats. MATERIALS AND METHODS: Pregnant female Wistar rats were randomly divided into a control and three experimental groups. The experimental groups received 20, 100 and 300 mg/L/day lead acetate via drinking water during lactation. Ovaries of the offspring were removed at 30, 60, 90 and 120 days of age, their weights recorded and fixed in Bouin's solution. Following tissue processing, 5 µm serial sections were stained with hematoxylin-eosin, and then, the numbers and diameters of ovarian follicles and corpora lutea were estimated. RESULTS: Ovary weights decreased significantly (p<0.05) in the 300 mg/L/day dose groups at 30, 60 and 90 days postnatal development. Significant dose-related decreases were seen in the numbers of primary, secondary and antral follicles in 100 (p<0.05) and 300 mg/L/day doses groups at 30 and 60 days of age (p<0.01). There was significant decrease in mean number of corpora lutea in the 100 (p<0.05) and 300 (p<0.01) mg/L/day dose groups at 60 days of age. It seems that neonatal lead treatment has transient effects on follicular development in the ovary of offspring and ovarian parameters gradually improve until 90 days of age. CONCLUSION: The present study showed that maternal lead acetate exposure affects prepubertal ovarian follicle development in a dose dependent manner, but ovarian parameters gradually improve during the postpubertal period.

The effect of palmitic acid on spatial learning and extinction in adult male rat.

The aim of the present study is for evaluating the effect of different doses of palmitic acid on spatial learning in T-maze. So, Wister adult male rats were used in five groups and considered 10 rats for each group. The first group as a control group was fed with ordinary diet. Four groups were fed with a diet containing palmitic acid (10%) for 1, 2, 3 and 4 weeks, then rats were trained for spatial learning task by using T-maze at subsequently 9 days based on standard method. The result showed that, spatial learning increased by diet containing palmitic acid 10% for 1, 2 and 3 weeks were significant (p<0.05). However, dietary palmitic acid effect on learning because palmitic acid via palmitoylation modifies numerous important neuronal protein including GAP-43, NMDA receptor, AMPA receptor and these receptors are critical role in learning.