Search

Phase-amplitude coupling (PAC) of local field potential (LFP) has been recognized as higher-order representation of brain states. Neuronal loss in the striatum leads to Parkinson’s disease (PD) symptoms and modifies LFP oscillation. However, PAC in the striatum of PD mouse model induced by 6-hydroxydopamne (6-OHDA) remained to be investigated. Male Swiss albino ICR mice were implanted with intracranial electrode and injected with 6-OHDA to the left striatum. Levodopa (L-dopa) (10 mg/kg, oral) was used for treatment once a day from day 15–19. Locomotor activity and resting LFP signals were selectively analyzed on day 15 and 19. One-way ANOVA revealed significant decreases in travelled distance induced by 6-OHDA on both days (p ≤ 0.05). However, the decreased travelled distances were significantly reversed by L-dopa. On day 15, LFP powers of theta, alpha, beta and low gamma waves were significantly increased by 6-OHDA injection and the powers of beta and low gamma were significantly reversed to control level by treatment with L-dopa. On day 19, LFP powers of delta, theta, alpha, beta and low gamma waves were significantly increased by 6-OHDA injection and the powers of low gamma were significantly reversed to control level by treatment with L-dopa. Theta-gamma PAC analyses also confirmed significant increase in modulation index (MI) induced by 6-OHDA on day 19. However, L-dopa failed to significantly reverse the MI to control level. These findings indicated theta-gamma coupling in the striatum of PD mouse model. Taken together, change in striatal theta-gamma PAC might be one of biomarkers in addition to hypokinesia and increased LFP powers that reflect disrupted neural mechanisms in PD mouse model.

Pueraria mirifica (PM) is a phytoestrogen-rich plant that was tested to establish if its phytosteroids could prevent estrogen dependent sarcopenia. The effect of PM on the estrogen levels, estrous cycle, toxicity, muscle mass, strength and endurance of extensor digitorum longus (EDL) and gastrocnemius muscles of ovariectomized rats was investigated. Adult female Wistar rats were divided into six groups: Sham-operated (SHAM); ovariectomized (OVX) fed with distilled water (PM0); OVX injected with 40 μg/kg estradiol benzoate (E40); (4-6) OVX fed with ethanolic extract of PM at doses of 50 (PM50), 500 (PM500) and 1000 (PM1000) mg/kg for 90 days. After treatment with all three doses of PM, no toxicity was detected to the hematopoietic system and liver function whereas the E40 group did show toxic effects. Treatment with 50 and 500 mg/kg of PM showed no effect on uterine hypertrophy and caused no arrest of the estrous cycle whereas treatment with estrogen and 1000 mg/kg of PM treatment did. The estrogen level, the cross sectional area of the EDL and the gastrocnemius muscle fiber strength and endurance were all significantly reduced in the PM0 group compared to that of the SHAM group (p

Neural adaptation associated with formation of morphine conditioned place preference remained largely unexplored. This study monitored longitudinal changes in neural signaling during pre-conditioning, conditioning and post-conditioning periods of morphine conditioned place preference (CPP) paradigm for investigation of adaptive mechanisms of opiate addiction. Male Swiss albino mice implanted with intracranial electrodes into the nucleus accumbens (NAc), striatum (STr) and hippocampus (HC) were used for recording of local field potentials (LFPs). Animals received a 10-day schedule for associative learning to pair the specific compartment of the chamber with morphine effects. Exploratory behavior and LFP signals were recorded during pre-conditioning (baseline level), conditioning (day 1, 5 and 10) and post-conditioning (day 1, 4 and 7) periods. Repeated measures one-way ANOVA followed by Tukey test revealed significant increases in number of visit and time spent in morphine compartment during post-conditioning days. Frequency analysis of LFP highlighted the increases in alpha activity (12 – 18 Hz) in the NAc from post-conditioning day 1 until day 7. Moreover, significantly increased coherent activities between the pair of NAc-HC were developed within gamma frequency range (35 – 42 Hz) on morphine conditioning day 10 and disappeared during post-conditioning days. Taken together, these findings emphasized NAc LFP signaling and neural connectivities between the NAc and HC associated with morphine CPP. These adaptive changes might underlie the formation of morphine conditioned place preference and behavioral consequences such as craving and relapse.

Functional role of the striatum in motor control has been widely studied. In addition, its involvement in reward function as a brain area in the dopamine system has also been mentioned. However, neural signaling in the striatum in response to consumption of emotional enhancing substances remained to be explored. This study aimed to investigate local field potential (LFP) of the striatum following morphine administration. Male Swiss albino mice implanted with electrode into the striatum were given an intraperitoneal injection of either saline or morphine (5 or 15 mg/kg). LFP and locomotor activity of individual animals were simultaneously recorded in the recording chamber following the administration. The inspection of LFP tracings revealed the increase in fast wave induced by morphine particularly at a high dose. Statistical analyses were performed using a one way ANOVA followed by Tukey post hoc test. Frequency analysis using Fast Fourier transform also confirmed a significant elevation of low gamma (30-44.9 Hz) activity. When analyzed in time domain, significant increase in low gamma power was observed from the 15th to 65th min following 15 mg/kg morphine treatment. Moreover, morphine treatment also exhibited a stimulating effect on locomotor speed. However, regression analyses revealed no significant correlation between low gamma power and locomotor speed. In summary, this study demonstrated the increase in low gamma oscillation in the striatum and this effect was not associated with locomotor activity of animals. Thus, it is possible that low gamma oscillation induced by morphine treatment is related with the reward function.

In the past decade, neural processing has been extensively studied in cognitive neuroscience. However, neural signaling in the nucleus accumbens (NAc) that might clarify reward process remained to be investigated. Male Swiss albino ICR mice implanted with intracranial electrodes into the NAc and the ventral tegmental area (VTA) were used for morphine administration and local field potential (LFP) recording. One-way ANOVA revealed significant increases in low (30.3-44.9 Hz) and high (60.5-95.7 Hz) gamma powers in the NAc following morphine administration (5 and 15 mg/kg, i.p.). These gamma activities oscillated independently with different time-course responses. Locomotor activity was also significantly increased by morphine administration. Regression analyses revealed that high gamma activity induced by morphine was positively correlated with distance travelled by animals. Low and high gamma powers were completely abolished by injection of naloxone, a non-specific opiate antagonist. Analysis of phase-amplitude coupling confirmed that slow oscillations at 1-4 Hz (delta) and 4-8 Hz (theta) for phase were found to significantly increase modulation index of broad (30.27-80.77 Hz) and narrow (59.48-70.34 Hz) frequency ranges for amplitude, respectively. Moreover, significant increases in coherence values between the NAc and the VTA during 30-40 min following morphine administration were seen for 22.46-44.90 Hz frequency range. Altogether, this study demonstrated changes of LFP oscillations in the NAc with low and high gamma activities, delta- and theta-gamma couplings and interplay with VTA in response to morphine administration. These findings represent neural signaling in the mesolimbic dopamine pathway that might process reward function.

Long term exposure to dexamethasone (Dx) is associated with brain damage especially in the hippocampus via the oxidative stress pathway. Previously, an ethanolic extract from Curcuma longa Linn. (CL) containing the curcumin constituent has been reported to produce antioxidant effects. However, its neuroprotective property on brain histology has remained unexplored. This study has examined the effects of a CL extract on the densities of cresyl violet positive neurons and glial fibrillary acidic protein immunoreactive (GFAP-ir) astrocytes in the hippocampus of Dx treated male rats. It showed that 21days of Dx treatment (0.5 mg/kg, i.p. once daily) significantly reduced the densities of cresyl violet positive neurons in the sub-areas CA1, CA3 and the dentate gyrus, but not in the CA2 area. However, CL pretreatment (100 mg/kg, p.o.) was found to significantly restore neuronal densities in the CA1 and dentate gyrus. In addition, Dx treatment also significantly decreased the densities of the GFAP-ir astrocytes in the sub-areas CA1, CA3 and the dentate gyrus. However, CL pretreatment (100 mg/kg, p.o.) failed to protect the loss of astrocytes in these sub-areas. These findings confirm the neuroprotective effects of the CL extract and indicate that the cause of astrocyte loss might be partially reduced by a non-oxidative mechanism. Moreover, the detection of neuronal and glial densities was suitable method to study brain damage and the effects of treatment.

Glucocorticoids arising from chronic stress and long-term inflammatory treatment with corticosteroids are both associated with neuropathology and cognitive impairments. Many previous studies have focused on changes in brain morphology and deficits in learning behavior. However, effects of long-term exposure to stress hormones on electrical brain signaling and sleep-wake patterns have remained largely unexplored. This study aimed to monitor electroencephalographic (EEG) patterns induced by prolonged dexamethasone exposure. Adult male Wistar rats implanted with electrodes on the skull over the frontal and parietal cortices were intraperitoneally injected with either saline or dexamethasone (0.5 mg/kg) once daily for 21 consecutive days. Longitudinal EEG recording was performed on day 6, 11, 16 and 21. Fast Fourier transform was used for frequency power analysis. One-way ANOVA revealed significant increases in parietal EEG power of slow frequencies (delta, theta and alpha) particularly, with the dominant theta activity seen as early as day 11 of dexamethasone treatment. Sleep-wake analysis on day 21 confirmed a significant reduction of rapid-eye movement (REM) sleep and increased slow frequency oscillations mainly in the parietal cortex during the awake period. The number of high-voltage spindles (HVSs) (6-10 Hz EEG oscillation) was significantly increased during awake and slow wave sleep (SWS) periods following dexamethasone treatment. These findings demonstrated that distinct frequency oscillations, sleep-wakefulness and sleep spindles may be parameters of neuropathology produced by long-term dexamethasone exposure. Early detection of these parameters might be predictive of neuropathology in long-term corticosteroid users.

Systemic or central administration of growth-hormone secretagogues (GHS) induces dense Fos expression in the arcuate nucleus but little or no Fos expression in the ventromedial hypothalamic nucleus, although both sites show intense expression of mRNA for the GHS receptor. Here, we recorded the electrical activity of single neurons from the arcuate nucleus and from the ventromedial hypothalamic nucleus in a rat hypothalamic slice preparation, and compared responses of these two populations to GHS. At both sites, the predominant neuronal response to GHS was a long-lasting excitation, indicating that GHS receptors at both sites are functional and similarly coupled to electrical excitation. We also tested neurons at both sites for their responses to neuropeptide Y and to somatostatin; at both sites the predominant response to each of these peptides was inhibitory. The arcuate cells that are activated by GHS include neuropeptide Y cells and growth hormone-releasing hormone cells. It seems possible that neuropeptide Y released in the ventromedial hypothalamus from the terminals of arcuate neurons counteracts the activation of ventromedial hypothalamic neurons by GHS in vivo, or that somatostatin released following liberation of growth hormone may do so.

Muscle weakness is common during menopause. Effective estrogen replacement was hypothesized to prevent sarcopenia. This study aimed to investigate the estrogen level, estrogen receptors (α and β) immunoreactivities, muscle mass and functions, and parvalbumin (PV) levels in the extensor digitorum longus (EDL) and the gastrocnemius muscles of ovariectomized rats. Adult female Wistar rats (12 weeks old) were divided into five groups: sham-operated (SHAM), and ovariectomized (E0) groups that received 10 weeks of estrogen replacements of 0 μg/kg (E0), 10 μg/kg (E10), 20 μg/kg (E20) and 40 μg/kg (E40). The estrogen levels, ER α and ER β immunoreactivities, muscle fiber sizes and contractivities and the PV levels were reduced in the E0 group, but increased in all the estrogen replacement groups in both muscles. This study indicated that the reduction of estrogen levels led to a decrease of both ER α and ER β resulting in a decline in muscle mass and PV levels. The decrease of PV levels affected muscle performance, whereas estrogen replacement increased both the ER α and ER β. The increase in the PV levels may result in an improvement of muscle performance. This may explain one mechanism of estrogen on muscle mass and strength in estrogen dependent sarcopenia.

Antidepressants have been used for treatment of ethanol withdrawal symptoms mainly in observational studies. However, cortical frequency oscillation of ethanol withdrawal treatment with antidepressants remained to be elucidated. This study aimed to identify surrogate biomarkers that represent intact biological or ethanol withdrawal processes and response to pretreatment with fluoxetine, a selective serotonin reuptake inhibitor, with quantitative methods. Adult male Wistar rats implanted with electrodes over the frontal and parietal cortices were rendered dependent on ethanol via modified liquid diet (MLD) containing ethanol. Then, ethanol-containing MLD was replaced with isocaloric ethanol-free MLD to induce ethanol withdrawal symptoms. Locomotor activity, sleep-wakefulness and spectral frequencies of electroencephalographic (EEG) pattern during ethanol-withdrawal period were analyzed. One-way ANOVA confirmed significant increases in locomotor activity and time spent in awake state and decreases time spent in non-rapid eye movement (NREM) sleep and REM-sleep during ethanol withdrawal period. Fast Fourier Transformation also revealed predominant increases in gamma spectral powers within both the frontal and parietal cortices during ethanol withdrawal. However, these changes, except sleep-wake disturbances, were significantly attenuated by fluoxetine pretreatment (10 mg/kg). The present study supports the hypothesis that serotonergic hypofunction may underlie most of ethanol withdrawal symptoms and proposes that electroencephalographic patterns are valid biomarkers for ethanol withdrawal evaluation and treatment.

The pathology of brain atrophy mediated by alcohol was investigated in all parts of the cerebral cortex (the frontal, parietal, temporal lobes and occipital cortex) by using two markers: parvalbumin (PV) and glial fibrillary acidic protein (GFAP). Three-month old male Wistar rats were divided into control (C) and alcohol-exposed groups. The control group received distilled water, whereas the alcohol-exposed groups received either a low dose (2g/kg body wt) or a high dose (5g/kg) of ethanol for periods of 21 days, 3 or 6 months. The brains of the animals were processed for immunohistochemistry using anti-parvalbumin and anti-GFAP antibodies and the number of PV immunoreactive (PV-ir) neurons and GFAP immunoreactive (GFAP-ir) astrocytes were counted per unit area. Results showed that all groups exposed to ethanol had significantly reduced numbers of PV-ir neurons in all parts of the cerebral cortex compared to those of the control group (p

Chronic excessive alcohol administration has been reported to be associated with diastolic dysfunction. Parvalbumin (PV) is a calcium-binding protein present in cardiac myocytes and involved in mediating relaxation. Therefore, alteration of PV levels may affect relaxation in cardiac myocytes. This study investigated the effects of alcohol administration on the levels of PV in the rat heart. Male Wistar rats weighing 200-250 g were divided into 2 groups: control (C) and alcohol-treated groups. The control group was provided with distilled water and the alcohol groups were provided with either a low dose (LD, 2g/kg) or high dose of ethanol (HD, 5 g/kg) once daily for 21 days, 3 months or 6 months. The PV levels in the ventricles were investigated by immunohistochemistry and Western blot analysis. In the 21-day ethanol-treated groups, parvalbumin immunoreactivity (PV-ir) and protein levels were not different when compared to the C, LD and HD groups. In the 3-month ethanol-treated groups, PV-ir and PV protein levels were decreased in both the LD and HD groups compared to that of the control group. In the 6-month ethanol-treated groups, PV-ir and PV protein levels decreased significantly in both the LD and HD groups (P0.05). This indicates that short-term ethanol treatment may not affect PV levels, whereas, long-term ethanol treatment clearly reduced PV levels. The decrease of PV was predominantly due to the direct toxic effects of alcohol rather than malabsorption caused by pathological changes in the duodenum and liver. The toxic effects of alcohol leading to a reduction of PV levels may lead to diastolic impairment.

Parvalbumin (PV), which is a small (12kDa) cytoplasmic calcium-binding protein, has been implicated in mediating relaxation in cardiac myocytes. The influence of aging and exercise on the distribution of PV in rat heart was investigated. Male Wistar rats aged 3, 6, 12 and 18-months were divided into sedentary and exercise groups. The exercise group underwent exercise in the form of regular swimming for 6 months. The hearts were processed for immunohistochemistry and Western blotting. The intensity of PV immunoreactivity was strong in the 9 and 12-month hearts and decreased in the 18-month hearts. The smallest amount was detected in the 24-month rat hearts when compared to those of the 9, 12 and 18-month rat hearts. Significantly less PV was detected in the 18 and 24-month hearts compared to the 12-month rat hearts (P

In this study, we examined the effects of restricted feeding and of central administration of an orexigenic ghrelin agonist GHRP-6 on peptide mRNA expression in the hypothalamus. We compared rats fed ad libitum with rats that were allowed food for only 2 h every day, and treated with a continuous chronic i.c.v. infusion of GHRP-6 or vehicle. Ad libitum fed rats exposed to GHRP-6 increased their food intake and body weight over 6 days, but, at the end of this period, neuropeptide Y mRNA expression in the arcuate nucleus was not different to that in control rats. By contrast, expression of neuropeptide Y mRNA in the arcuate nucleus was elevated in food-restricted rats, consistent with the interpretation that increased expression reflects increased hunger. However, neuropeptide Y mRNA expression was no greater in food-restricted rats infused with GHRP-6 than in food-restricted rats infused with vehicle; thus if the drive to eat was stronger in rats infused with GHRP-6, this was not reflected by higher levels of neuropeptide Y mRNA expression. Expression of vasopressin mRNA and corticotrophin releasing factor (CRF) mRNA in the paraventricular nucleus (PVN) was not changed by food restriction. GHRP-6 infusion increased CRF mRNA expression in ad libitum rats only.

The pharmacological properties of the ephedrine derivative pseudoephedrine were investigated at the nuclear level. Following intraperitoneal injection of Sprague‐Dawley rats with pseudoephedrine, Fos induction was measured in various brain areas by Western blots and immunocytochemistry. Pseudoephedrine induced Fos-like immunoreactivity in the nucleus accumbens and striatum in a time and concentration-dependent manner with maximal effect at 60 mg:kg 2 h after injection. Immunocytochemical studies confirmed that the majority of the signal was detectable in the nucleus accumbens and striatum. Pre-injection with the D1 dopamine receptor antagonist SCH23390 partially and completely blocked pseudoephedrine-induced Fos-like immunoreactivity in the striatum and nucleus accumbens, respectively, suggesting that the action of pseudoephedrine is mediated via dopamine release and results in the activation of D1 dopamine receptors. With the exception of the higher doses required, the actions of pseudoephedrine were similar to those previously described for the psychostimulant amphetamine. © 1999 Elsevier Science Ltd. All rights reserved.