Nasal application of kisspeptin-54 mitigates motor deficits by reducing nigrostriatal dopamine loss in hemiparkinsonian rats.

Parkinson's Disease is a progressive neurodegenerative disorder characterized by motor symptoms resulting from the loss of nigrostriatal dopaminergic neurons. Kisspeptins (KPs) are a family of neuropeptides that are encoded by the Kiss-1 gene, which exert their physiological effects through interaction with the GPR54 receptor. In the current investigation, we investigated the prospective protective effects of central KP-54 treatments on nigrostriatal dopaminergic neurons and consequent motor performance correlates in 6-hydroxydopamine (6-OHDA)-lesioned rats. Male adult Sprague Dawley rats underwent stereotaxic injection of 6-OHDA into the right medial forebrain bundle to induce hemiparkinsonism. Following surgery, rats received chronic central treatments of nasal or intracerebroventricular KP-54 (logarithmically increasing doses) for seven consecutive days. Motor performance was evaluated seven days post-surgery utilizing the open field test and catalepsy test. The levels of dopamine in the striatum were determined with mass spectrometry. Immunohistochemical analysis was conducted to assess the immunoreactivities of tyrosine hydroxylase (TH) and the GPR54 in the substantia nigra. The dose-response curve revealed a median effective dose value of ≈3 nmol/kg for both central injections. Due to its non-invasive and effective nature, nasal administration was utilized in the second phase of our study. Chronic administration of KP-54 (3nmol/kg, nasally) significantly protected 6-OHDA-induced motor deficits. Nasal KP-54 attenuated the loss of nigrostriatal dopaminergic neurons induced by 6-OHDA. Additionally, significant correlations were observed between motor performance and nigrostriatal dopamine levels. Immunohistochemical analysis demonstrated the localization of the GPR54 within TH-positive nigral cells. These findings suggest the potential efficacy of central KP-54 on motor impairments in hemiparkinsonism.

Effects of transcranial direct current stimulation on the glutamatergic pathway in the male rat hippocampus after experimental focal cerebral ischemia.

This study aimed to assess the focal cerebral ischemia-induced changes in learning and memory together with glutamatergic pathway in rats and the effects of treatment of the animals with transcranial Direct Current Stimulation (tDCS). One hundred male rats were divided into five groups as sham, tDCS, Ischemia/Reperfusion (IR), IR + tDCS, and IR + E-tDCS groups. Learning, memory, and locomotor activity functions were evaluated by behavioral experiments in rats. Glutamate and glutamine levels, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptor (AMPAR1), N-Methyl-D-Aspartate receptors (NMDAR1 and NMDAR2A), vesicular glutamate transporter-1 (VGLUT-1), and excitatory amino acid transporters (EAAT1-3) mRNA expressions in hippocampus tissues were measured. Ischemic areas were analyzed by TTC staining. The increase was observed in IR + tDCS, and IR + E-tDCS groups compared to the IR group while a significant decrease was observed in IR group compared to the sham in the locomotor activity, learning, and memory tests. While glutamate and glutamine levels, AMPAR1, NMDAR1, NMDAR2A, VGLUT1, and EAAT1 mRNA expressions were significantly higher in IR group compared to the sham group, it was found to be significantly lower in IR + tDCS and IR + E-tDCS groups compared to the IR group. EAAT2 and EAAT3 mRNA expressions were significantly higher in IR + tDCS and IR + E-tDCS groups compared to the IR group. Ischemic areas were significantly decreased in IR + tDCS and IR + E-tDCS groups compared to the IR group. Current results suggest that tDCS application after ischemia improves learning and memory disorders and these effects of tDCS may be provided through transporters that regulate glutamate levels.

Acetyl-L-carnitine attenuates chronic ethanol-induced oxidative stress, ER stress and apoptosis in rat gastric tissue.

Consuming alcohol affects almost all organs. Acetaldehyde, formed as the main product as a result of alcohol metabolism, causes the production of free superoxide radicals when oxidized, and accordingly oxidative and apoptotic processes are triggered. There are studies showing that carnitine has effects on oxidative and apoptotic processes that occur in various conditions. However, the mechanisms showing the effects of L-carnitine on these effects of alcohol have not been fully elucidated. In our study, the effects of acetyl-L-carnitine administration on the molecular mechanisms of oxidative stress, endoplasmic reticulum stress, and apoptotic parameters in gastric tissue of rats chronically exposed to alcohol were investigated. Hematoxylin-eosin staining was used for histopathological studies. Endoplasmic reticulum stress markers were detected with immunohistochemical staining and western blotting. Apoptotic index was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Total oxidant and antioxidant status were examined by ELISA. Our results showed that chronic alcohol administration caused a significant increase in TOS levels, an indicator of oxidative stress, the levels of ER-stress-associated proteins XBP1, GRP78, and CHOP, and % apoptotic index values in rat gastric tissues. Additionally, it was determined that acetyl-L-carnitine administration caused an improvement in those values. Based on our data, we can conclude that acetyl-L-carnitine has a tissue protective effect by scavenging free oxygen radicals and reducing ER stress-related proteins XBP1, GRP78, and CHOP and apoptosis in chronic ethanol-administered rats, and that this natural antioxidant may be beneficial in the treatment of oxidative stress-induced diseases.

L-Carnitine improves mechanical responses of cardiomyocytes and restores Ca2+ homeostasis during aging.

L-Carnitine (ß-hydroxy-γ-trimethylaminobutyric acid, LC) is a crucial molecule for the mitochondrial oxidation of fatty acids. It facilitates the transport of long-chain fatty acids into the mitochondrial matrix. The reduction in LC levels during the aging process has been linked to numerous cardiovascular disorders, including contractility dysfunction, and disrupted intracellular Ca2+ homeostasis. The aim of this study was to examine the effects of long-term (7 months) LC administration on cardiomyocyte contraction and intracellular Ca2+ transients ([Ca2+]i) in aging rats. Male albino Wistar rats were randomly assigned to either the control or LC-treated groups. LC (50 mg/kg body weight/day) was dissolved in distilled water and orally administered for a period of 7 months. The control group received distilled water alone. Subsequently, ventricular single cardiomyocytes were isolated, and the contractility and Ca2+ transients were recorded in aging (18 months) rats. This study demonstrates, for the first time, a novel inotropic effect of long-term LC treatment on rat ventricular cardiomyocyte contraction. LC increased cardiomyocyte cell shortening and resting sarcomere length. Furthermore, LC supplementation led to a reduction in resting [Ca2+]i level and an increase in the amplitude of [Ca2+]i transients, indicative of enhanced contraction. Consistent with these results, decay time of Ca2+ transients also decreased significantly in the LC-treated group. The long-term administration of LC may help restore the Ca2+ homeostasis altered during aging and could be used as a cardioprotective medication in cases where myocyte contractility is diminished.

Transcranial direct current stimulation alleviates nociceptive behavior in male rats with neuropathic pain by regulating oxidative stress and reducing neuroinflammation.

Transcranial direct curent stimulation (tDCS) and trans-spinal direct current stimulation (tsDCS) are promising therapies for pain that can alter the excitability of neuronal activity in cerebral cortex. The aim of the study is to investigate the therapeutic effects of direct current stimulation (DCS) over the spinal cord and cerebral cortex on oxidative stress and neuroinflammation in rats with chronic constriction injury (CCI). Male Wistar rats were randomly divided into four experimental groups: Sham, CCI, CCI + tDCS and CCI + tsDCS. The neuropathic pain model was induced by using the CCI model. Rats with neuropathy were treated with cathodal tDCS and tsDCS stimulations consisting of 0.5 mA for 30 min a day for 7 days from day 8 onwards. Locomotor activity was measured by open-field test and nociceptive behavior was assessed by hot-plate, tail-flick and Randall-Selitto tests. Following the behavioral experiments, total oxidant capacity (TOC), total antioxidant capacity (TAC) and proinflammatory cytokine levels were evaluated in spinal cord and cerebral cortex tissues. The CCI model induced significant mechanical and thermal hyperalgesia. Nociceptive behaviors in rats with CCI were reversed by DCS treatment. Higher TOC and lower TAC levels were detected in the spinal cord and cerebral cortex tissues of the CCI rats compared to the control. tsDCS treatment amended oxidant/antioxidant status. Moreover, tsDCS modulated the central levels of Tumor necrosis factor-α (TNF-α), interleukin 1-beta (IL-1ß), IL-6 and IL-18. tsDCS stimulation showed better therapeutic effect on neuropathic pain by regulating oxidant/antioxidant levels and reducing neuroinflammation. DCS, especially at spinal level, may be a promising therapeutic strategy that can be used alone or in combination with other effective treatments for alleviating neuropathic pain.

Investigation of Cyclo-Z Therapeutic Effect on Insulin Pathway in Alzheimer's Rat Model: Biochemical and Electrophysiological Parameters.

Cyclo (his-pro-CHP) plus zinc (Zn+2) (Cyclo-Z) is the only known chemical that increases the production of insulin-degrading enzyme (IDE) and decreases the number of inactive insulin fragments in cells. The aim of the present study was to systematically characterize the effects of Cyclo-Z on the insulin pathway, memory functions, and brain oscillations in the Alzheimer's disease (AD) rat model. The rat model of AD was established by bilateral injection of Aß42 oligomer (2,5nmol/10µl) into the lateral ventricles. Cyclo-Z (10mg Zn+2/kg and 0.2mg CHP/kg) gavage treatment started seven days after Aß injection and lasted for 21 days. At the end of the experimental period, memory tests and electrophysiological recordings were performed, which were followed by the biochemical analysis. Aß42 oligomers led to a significant increase in fasting blood glucose, serum insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and phospho-tau-Ser356 levels. Moreover, Aß42 oligomers caused a significant decrement in body weight, hippocampal insulin, brain insulin receptor substrate (IRS-Ser612), and glycogen synthase kinase-3 beta (GSK-3ß) levels. Also, Aß42 oligomers resulted in a significant reduction in memory. The Cyclo-Z treatment prevented the observed alterations in the ADZ group except for phospho-tau levels and attenuated the increased Aß42 oligomer levels in the ADZ group. We also found that the Aß42 oligomer decreased the left temporal spindle and delta power during ketamine anesthesia. Cyclo-Z treatment reversed the Aß42 oligomer-related alterations in the left temporal spindle power. Cyclo-Z prevents Aß oligomer-induced changes in the insulin pathway and amyloid toxicity, and may contribute to the improvement of memory deficits and neural network dynamics in this rat model.

Effect of perinatal and postnatal thiamine deficiency on auditory pathway of the Wistar-Albino rats

Abstract Objective: In this study, we created an animal model to demonstrate the effects of thiamine on the hearing pathways of new-borns during pregnancy and lactation by inducing a dietary thiamine deficiency in the mother. Methods: The study included 16 female Wistar albino rats. The animals were separated into four groups and provided the appropriate amounts of dietary thiamine according to their groups during pre-pregnancy, pregnancy, and lactation periods. Three pups from each mother were included in the study, and 12 pups were selected from each group. On the fortieth day after birth, the auditory pathways of 48 pups in the 4 groups were examined electro physiologically and ultra-structurally. Results: In Group N-N, morphology of hair cells stereocilia degeneration was not obtained in all turns of cochlea. In Group N-T, Inner Hair Cells (IHCs) and Outher Hair Cells (OHCs) stereocilia didn't show degeneration in all turns of cochlea but had rupture inrows of HCs stereocilia. In group T-N IHCs stereocilia less degeneration was observed in all turns of cochlea. OHC stereocilia partial loss was observed only in basal turn of cochlea. In Group T-T IHCs stereocilia was observed less degeneration and rupture in all turns of cochlea. Conclusion: Thiamine is vital for the development of cochlear hair cells during both prenatal and postnatal periods. Even partial deficiency of thiamine causes significant degeneration to the auditory pathway. Level of evidence: The level of evidence of this article is 5. This article is an experimental animal and laboratory study.

Effect of perinatal and postnatal thiamine deficiency on auditory pathway of the Wistar-Albino rats.

OBJECTIVE: In this study, we created an animal model to demonstrate the effects of thiamine on the hearing pathways of new-borns during pregnancy and lactation by inducing a dietary thiamine deficiency in the mother. METHODS: The study included 16 female Wistar albino rats. The animals were separated into four groups and provided the appropriate amounts of dietary thiamine according to their groups during pre-pregnancy, pregnancy, and lactation periods. Three pups from each mother were included in the study, and 12 pups were selected from each group. On the fortieth day after birth, the auditory pathways of 48 pups in the 4 groups were examined electro physiologically and ultra-structurally. RESULTS: In Group N-N, morphology of hair cells stereocilia degeneration was not obtained in all turns of cochlea. In Group N-T, Inner Hair Cells (IHCs) and Outher Hair Cells (OHCs) stereocilia didn't show degeneration in all turns of cochlea but had rupture inrows of HCs stereocilia. In group T-N IHCs stereocilia less degeneration was observed in all turns of cochlea. OHC stereocilia partial loss was observed only in basal turn of cochlea. In Group T-T IHCs stereocilia was observed less degeneration and rupture in all turns of cochlea. CONCLUSION: Thiamine is vital for the development of cochlear hair cells during both prenatal and postnatal periods. Even partial deficiency of thiamine causes significant degeneration to the auditory pathway. LEVEL OF EVIDENCE: The level of evidence of this article is 5. This article is an experimental animal and laboratory study.

The effect of increase in blood glucose level on hearing loss

Abstract Objective: Previous studies have shown that hearing function is also vulnerable to the effects of diabetes mellitus which can be shown by brainstem auditory evoked potential and distortion product otoacoustic emission recordings. This study aimed to investigate the changes of brainstem auditory evoked potential and distortion product otoacoustic emission in hyperglycemia and whether there is a relationship between reactive oxygen substances production and hearing deterioration in the rat model. Methods: 25 streptozotocin induced diabetic rats were divided into three groups: control, high blood glucose, and diabetes mellitus. Brainstem auditory evoked potential and distortion product otoacoustic emission were recorded, and thiobarbituric acid reactive substances levels were measured in the brainstem tissue. Results: At 8 kHz, the latencies of I, II, III, IV, and V brainstem auditory evoked potential waves in high blood glucose and diabetes mellitus groups were elongated, at 16 kHz, only these wave latencies of the diabetes mellitus group were prolonged compared with the control group. A significant decrease was also found in distortion product otoacoustic emission amplitudes at 4, 6, 8, and 10 kHz in the high blood glucose and diabetes mellitus groups compared to the control group. There was a significant increase in thiobarbituric acid reactive substances values due to the increase in blood glucose levels in the high blood glucose and diabetes mellitus groups compared to the control group. Conclusion: These results suggested that high blood glucose levels may cause hearing impairment not only in the diabetic state but also in the period of hyperglycemia before the onset of manifest diabetes mellitus and reactive oxygen substances may play an important role in the pathophysiology of diabetes mellitus. We suggest that regulating high glucose levels even before the onset of manifest diabetes mellitus may prevent hazardous effects on hearing function. Level of evidence: Level 3.

Effects of biotin deficiency on short term memory: The role of glutamate, glutamic acid, dopamine and protein kinase A.

Insufficient dietary biotin intake, biotinidase deficiency, drug-biotin interactions can cause biotin deficiency which may result in central nervous system dysfunctions. We hypothesized that biotin deficiency could disrupt learning and memory functions by altering glutamate, glutamine, dopamine levels and protein kinase A (PKA) activity in the hippocampus. Sixteen female and 4 male Wistar rats were mated and females were separated into 4 groups. Three pups were selected from each mother and a total of 48 pups were divided into the following experimental groups. NN group, normal diet in the prenatal and postnatal period. NB group, normal diet in the prenatal and a biotin-deficient diet in the postnatal period. BN group: biotin-deficient diet in the prenatal and a normal diet in the postnatal period, BB group: biotin-deficient diet in both the prenatal and postnatal period. Open Field, Y-Maze, Object Location, and Novel Object Recognition Tests were performed in all groups and rats were sacrificed. Glutamine, glutamate, dopamine levels and PKA activity were analyzed in the hippocampi. In the open field test, distance and velocity values of NB, BN and BB groups were decreased with respect to the NN group. Learning and memory functions of NB, BN and BB groups were found to be impaired in behavioral tests. Dopamine levels and PKA activity were also decreased in all rat pups fed with a biotin deficient diet. In conclusion, we demonstrated that biotin deficiency deteriorates short-term memory and locomotor activity. This impairment may relate to decreased dopamine levels and PKA activity in the hippocampus.

The Role of Acetylcholine on the Effects of Different Doses of Sulfite in Learning and Memory.

In this study, the effects of different doses of sulfite on learning, memory, and long term potentiation as well as the relationship of these effects with acetylcholine pathways, Arc and synapsin 1 levels were investigated. Sixty male Wistar albino rats were randomly divided into three groups as control, S100, and S260. Sodiummetabisulfite (S100;100 mg/kg/day, S260;260 mg/kg/day) was given by oral administration. Behavioral changes were evaluated. After long term potentiation recordings from the perforant pathway-dentate gyrus synapses, animals were sacrificed. Acetylcholinesterase activity, choline acetyltransferase activity, acetylcholine level as well as Arc and Synapsin 1 expressions were analyzed on the hippocampi. The total distance and average velocity values in the open field and Morris water maze tests increased in the sulfite groups, while the discrimination index in the novel object recognition test decreased compared to controls. Acetylcholine levels and choline acetyltransferase activity were also increased in the sulfite groups, while acetylcholinesterase activity was decreased compared to controls. Sulfite intake attenuated long term potentiation in the hippocampus. It has been observed that the excitatory postsynaptic potential slope and population spike amplitude of the field potentials obtained in sulfite groups decreased. This impairment was accompanied by a decrease in Arc and synapsin 1 expressions. In conclusion, it has been shown that sulfite intake in adults impairs learning and memory, possibly mediated by the cholinergic pathway. It is considered that the decrement in Arc and synapsin expressions may play a role in the mechanism underlying the impairment in long term potentiation caused by toxicity.

The effect of increase in blood glucose level on hearing loss.

OBJECTIVE: Previous studies have shown that hearing function is also vulnerable to the effects of diabetes mellitus which can be shown by brainstem auditory evoked potential and distortion product otoacoustic emission recordings. This study aimed to investigate the changes of brainstem auditory evoked potential and distortion product otoacoustic emission in hyperglycemia and whether there is a relationship between reactive oxygen substances production and hearing deterioration in the rat model. METHODS: 25 streptozotocin induced diabetic rats were divided into three groups: control, high blood glucose, and diabetes mellitus. Brainstem auditory evoked potential and distortion product otoacoustic emission were recorded, and thiobarbituric acid reactive substances levels were measured in the brainstem tissue. RESULTS: At 8 kHz, the latencies of I, II, III, IV, and V brainstem auditory evoked potential waves in high blood glucose and diabetes mellitus groups were elongated, at 16 kHz, only these wave latencies of the diabetes mellitus group were prolonged compared with the control group. A significant decrease was also found in distortion product otoacoustic emission amplitudes at 4, 6, 8, and 10 kHz in the high blood glucose and diabetes mellitus groups compared to the control group. There was a significant increase in thiobarbituric acid reactive substances values due to the increase in blood glucose levels in the high blood glucose and diabetes mellitus groups compared to the control group. CONCLUSION: These results suggested that high blood glucose levels may cause hearing impairment not only in the diabetic state but also in the period of hyperglycemia before the onset of manifest diabetes mellitus and reactive oxygen substances may play an important role in the pathophysiology of diabetes mellitus. We suggest that regulating high glucose levels even before the onset of manifest diabetes mellitus may prevent hazardous effects on hearing function. LEVEL OF EVIDENCE: Level 3.

Does Resveratrol Prevent Sevoflurane Toxicity in Newborn Rats?

Inhalation anesthetics have been shown to cause neurodevelopmental disorders and neurotoxic effects. In this study, we aimed to investigate the effect of resveratrol on the possible neurotoxic effect of sevoflurane and the brain-derived neurotrophic factor (BDNF) pathway in newborn rats. The animals were divided into four groups: control, sevoflurane, sevoflurane+resveratrol 25 mg/kg, and sevoflurane+resveratrol 50 mg/kg. The groups that received anesthesia were given 3% sevoflurane for 2 h on the postnatal seventh, eighth, and ninth days. Control gas was applied to the control group. The Morris water maze (MWM) test was performed on postnatal 35th day. After performing the open field test on the postnatal 41st day, the animals were dissected, and the hippocampal BDNF levels were determined by Western blot method. In the MWM test, there was a significant decrease in the time spent in the target quadrant in the sevoflurane anesthesia group compared with control group. This reduction was reversed with the resveratrol pretreatment. Sevoflurane exposure significantly decreased hippocampal BDNF levels compared with the control group. The resveratrol 25 mg/kg pretreatment did not reverse this reduction, whereas resveratrol 50 mg/kg ameliorated this impairment. Sevoflurane did not cause any significant difference in the rats' performance in the open field test. However, 50 mg/kg resveratrol pretreatment caused a statistically significant increase in this performance. Our results showed that sevoflurane impaired learning and memory functions in newborn rats and resveratrol reversed this deterioration. Also BDNF might play a role in this beneficial effect of resveratrol.

Comparison of the therapeutic effects of erythropoietin and acetyl-l-carnitine on sciatic nerve injury in rats.

AIM: We aimed to investigate the effects of erythropoietin, acetyl-l-carnitine, and their combination on nerve regeneration in experimental peripheral nerve injury. METHODS: Rats were randomly divided into five groups - sham-operated (S), sciatic nerve crush injury (C), C + acetyl-l-carnitine (ALCAR), C + erythropoietin (EPO), and C + EPO + ALCAR. ALCAR (50 mg/kg/day) was administered intraperitoneally, and EPO (5000 U/kg) was injected subcutaneously for 10 days. Functional recovery was evaluated using walking track analysis (sciatic functional index [SFI]), somatosensory evoked potentials (SEPs), thiobarbituric acid reactive substance (TBARS) assay, and caspase-3 and S100 immunoreactivities. RESULTS: In SFI analyses, delayed functional recovery was observed in the C group, whereas the functional recovery of rats treated with EPO and ALCAR significantly improved. The latencies of the SEP components were significantly prolonged in C group. In the treatment groups (C + EPO, C + ALCAR, and C + EPO + ALCAR), all recorded values of SEP components significantly decreased. TBARS levels in C group were significantly higher than those in the S group. EPO and ALCAR administration significantly decreased TBARS levels. Caspase-3 immunoreactivity was increased in the C group, whereas it was decreased in the treatment groups. S100 immunolabelling was significantly decreased in the C group. EPO and ALCAR administration caused an increase in the amount of S100-positive cells in all treatment groups. CONCLUSION: EPO and ALCAR administration could accelerate sciatic nerve repair by reducing apoptosis and lipid peroxidation and promoting myelinization. Although both EPO and ALCAR had positive effects on nerve healing, their combined efficacy had no statistically significant effect on peripheral nerve regeneration.

Vortioxetine ameliorates motor and cognitive impairments in the rotenone-induced Parkinson's disease via targeting TLR-2 mediated neuroinflammation.

Parkinson's disease (PD) is characterized by motor and non-motor symptoms associated with dopaminergic and non-dopaminergic injury. Vortioxetine is a multimodal serotonergic antidepressant with potential procognitive effects. This study aimed to explore the effects of vortioxetine on motor functions, spatial learning and memory, and depression-like behavior in the rotenone-induced rat model of PD. Male Sprague-Dawley rats were daily administered with the rotenone (2 mg kg-1, s.c.) and/or vortioxetine (10 mg kg-1, s.c.) for 28 days. Motor functions (rotarod, catalepsy, open-field), depression-like behaviors (sucrose preference test), anxiety (elevated plus maze), and spatial learning and memory abilities (novel object recognition and Morris water maze) were evaluated in behavioral tests. Then immunohistochemical, neurochemical, and biochemical analysis on specific brain areas were performed. Vortioxetine treatment markedly reduced rotenone-induced neurodegeneration, improved motor and cognitive dysfunction, decreased depression-like behaviors without affecting anxiety-like parameters. Vortioxetine also restored the impaired inflammatory response and affected neurotransmitter levels in brain tissues. Interestingly, vortioxetine was thought to trigger a sort of dysfunction in basal ganglia as evidenced by increased Toll-like receptor-2 (TLR-2) and decreased TH immunoreactivity only in substantia nigra tissue of PD rats compared to the control group. The present study indicates that vortioxetine has beneficial effects on motor dysfunction as well as cognitive impairment associated with neurodegeneration in the rotenone-induced PD model. Possible mechanisms underlying these beneficial effects cover TLR-2 inhibition and neurochemical restoration of vortioxetine.

The influence of syringic acid treatment on total dopamine levels of the hippocampus and on cognitive behavioral skills.

BACKGROUND: Natural polyphenols have been investigated and are claimed to be mediators of the relationship between dopamine (DA) and memory. Therefore, we aimed to measure and evaluate the effect of syringic acid (SA) on DA expression by behavioral tests related to short-term and recognition memory in Wistar rats. METHODS: Rats were randomly assigned to control (0.5 cc corn oil, n = 10), SA (25 mg/kg/day, o.g, n = 10), Deltamethrin (DTM) (1.28 mg/kg/day o.g, n = 10) and DTM (1.28 mg/kg/day o.g, n = 10) + SA (25 mg/kg/day) groups. The Y-maze and Novel Object Recognition (NOR) tests were performed to assess cognitive and behavioral functions in the rats. Dopamine levels in the hippocampus were measured by mass spectrometry. RESULTS: Syringic acid significantly increased DA (5.45 ± 1.06 ng/ml, p = 0.0026, p < 0.05) compared with the other groups. SA increased the percent alternation (34.85 ± 0.72%, p < 0.05), time spent in the novel arm (2.88 ± 0.18 min, p < 0.05), and frequency of novel arm entries (44.91 ± 2.28%, p < 0.05), of the rats after the Y-maze test. The SA elevated the discrimination index (70.42 ± 3.59%, p < 0.001), and exploration time (30.44 ± 1.8 sec, p < 0.05) in the NOR test, and increased the short term and recognition memory in behavioral tests. CONCLUSION: Our findings support the hypothesis that SA-induced DA levels of the hippocampus may facilitate recognition and short-term memory in Wistar rats through the activation of dopaminergic receptors or pathways during the learning process, and that this can be seen in the cognitive behavior of SA-treated rats.

Effects of adropin on learning and memory in rats tested in the Morris water maze.

Adropin is a secreted peptide, which is composed of 43 amino acids and shows an effective role in regulating energy metabolism and insulin resistance. Motor coordination and locomotor activity were improved by adropin in the cerebellum. However, it is not known whether adropin administration has an effect on spatial learning and memory. In this study, we investigated the effect of adropin on spatial learning and memory and characterized the biochemical properties of adropin in the hippocampus. Thirty male Sprague-Dawley rats were randomly divided into two groups as control and adropin groups. The control group received 0.9% NaCl intracerebroventricular for 6 days, while the adropin groups received 1 nmol of adropin dissolved in 0.9% NaCl (for 6 days). The Morris water maze, Y maze, and object location recognition tests were performed to evaluate learning and memory. Also, the locomotor activity tests were measured to assess the motor function. The expression of Akt, phospho-Akt, CREB, phospho-CREB, Erk1/2, phospho-Erk1/2, glycogen synthase kinase 3 ß (GSK3ß), phospho-GSK3ß, brain-derived neurotrophic factor (BDNF), and N-methyl-d-aspartate receptor NR2B subunit were determined in the hippocampal tissues by using western blot. Behavior tests showed that adropin significantly increase spatial memory performance. Meanwhile, the western blot analyses revealed that the phosphorylated form of the Akt and CREB were enhanced with adropin administration in the hippocampus. Also, the expression of BDNF showed an enhancement in adropin group in comparison to the control group. In conclusion, we have shown for the first time that adropin exerts its enhancing effect on spatial memory capacity through Akt/CREB/BDNF signaling pathways.

Neuropeptide-S affects cognitive impairment and depression-like behavior on MPTP induced experimental mouse model of Parkinson's disease

Background/aim: The present study proposes to investigate the effect of neuropeptide­S (NPS) on cognitive functions and depression-like behavior of MPTP-induced experimental model of Parkinson's disease (PD). Materials and methods: Three-month-old C57BL/6 mice were randomly divided into three groups as; Control, Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and MPTP + NPS 0.1 nmol (received intraperitoneal injection of MPTP and intracerebroventricular injection of NPS, 0.1 nmol for seven days). The radial arm maze and pole tests were carried out, and the levels of tyrosine hydroxylase (TH) were determined using western blotting. A mass spectrometer was used to measure the levels of dopamine, glutamic acid, and glutamine. Results: The T-turn and time to descend enhanced in MPTP group, while these parameters were decreased by NPS treatment. In the MPTP group, the number of working memory errors (WME) and reference memory errors (RME) increased, whereas NPS administration decreased both parameters. Sucrose preference decreased in the MPTP group while increasing in the NPS group. MPTP injection significantly reduced dopamine, glutamic acid, and glutamine levels. NPS treatment restored the MPTP-induced reduction in glutamine and glutamic acid levels. Conclusion: NPS may be involved in the future treatment of cognitive impairments and depression-like behaviors in PD.

The effect of chronic neuropeptide-S treatment on non-motor parameters in experimental model of Parkinson's disease.

AIM: Besides motor impairment, non-motor symptoms including cognitive decline, anxiety, and depression are observed in Parkinson's Disease (PD). The aim of this study was to investigate whether chronic administration of central neuropeptide-S (NPS) improves non-motor symptoms in 6-hydroxydopamine (6-OHDA)-induced parkinsonian rats. MATERIAL AND METHODS: Experimental PD was utilized by unilateral stereotaxic injection of the 6-OHDA into the medial forebrain bundle (MFB), while the sham-operated animals underwent the same surgical procedures. NPS (1 nmol) or vehicle was daily administered through an intracerebroventricular (icv) cannula for 7 days. Radial arm maze (RAM) test was used to evaluate the working memory; whereas, elevated plus maze (EPM) test and sucrose preference test were used to monitor the anxiety and depression status, respectively. The levels of dopamine, glutamic acid, and glutamine was determined in harvested striatal and hippocampal tissue samples. The immunoreactivities for tyrosine hydroxylase (TH) was determined using immunohistochemistry. RESULTS: In the RAM test, the 6-OHDA-induced increases in the reference and working memory errors were reduced by the central NPS administration. The decreased sucrose preference in the parkinsonian rats was increased by centrally administered NPS. The levels of dopamine levels in striatum and hippocampus were decreased in the parkinsonian rats, however, they were not altered by the centrally administered NPS. Additionally, NPS treatment significantly attenuated the 6-OHDA-induced loss of TH neuronal number. CONCLUSION: Consequently, NPS appears to be a therapeutic candidate for the treatment of non-motor complications of PD.

Possible effects of different doses of 2.1 GHz electromagnetic radiation on learning, and hippocampal levels of cholinergic biomarkers in Wistar rats.

The present study evaluated whether short-term exposure to different doses of 2.1 GHz radiofrequency electromagnetic radiation (RF-EMR) has different effects on rats' behaviour and hippocampal levels of central cholinergic biomarkers. Animals were divided into three equal groups namely; group 1 was sham-exposed group, group 2-3 were exposed to 45 V/m and 65 V/m doses of 2.1 GHz frequency for 1 week respectively. Numerical dosimetry simulations were carried out. Object location and Y-maze were used as behavioural tasks. The protein and mRNA expression levels of AChE, ChAT, and VAChT, in the hippocampus were tested using Western Blotting and Real-Time PCR. The impairment performance of rats subjected to 65 V/m dose of 2.1 GHz RF-EMR in both object location and Y-maze tasks was observed. The hippocampal levels of AChE, ChAT, and VAChT, were significantly lower in rats exposed to 65 V/m dose of 2.1 GHz RF-EMR than others. The stronger effect of "65 V/m" dose on both rat's hippocampal-dependent behavioural performances and hippocampal levels of cholinergic biomarkers may be due to the stronger effect of "65 V/m" dose where rats' snouts were located at the nearest distance from the monopole antenna. Furthermore, the simulated SAR values were high for 65 V/m electric-field strengths. For the first time, we report the potential dose-dependent effects of short-term exposure to 2.1 GHz radiation on rat's behavioural performances as well as hippocampal levels of cholinergic biomarkers. Further studies are needed to understand the mechanisms by which RF-EMR influences the function of the central cholinergic system in the brain.