Differences in Neurodegeneration Between Kainic Acid-Injected GAERS and Wistar Rats.

AIM: To compare neurodegenerative changes using the Fluoro-Jade B staining, following status epilepticus induced by intraamygdaloid injection of kainic acid in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and non-epileptic control Wistar rats. MATERIAL AND METHODS: A single unilateral intra-amygdaloid kainic acid (750 ng) was administered in adult male GAERS and Wistar rats to induce status epilepticus. We recorded electroencephalogram (EEG) and behavioral changes throughout the experiments. After 1 week of the kainic acid injection, rats were sacrificed, and the brains were removed. We obtained 20λm sections and processed them for Fluoro-Jade B and Nissl staining, which were evaluated semi-quantitatively. RESULTS: Following kainic acid injections, status epilepticus developed in all rats. In GAERS rats, motor seizures were considerably delayed, with no statistically significant difference in the number of seizures. However, statistically significant differences were observed in the Fluoro-Jade B staining in GAERS rats between contralateral and ipsilateral sides of the CA3, CA1, somatosensory cortex, entorhinal cortex, piriform cortex, reticular nucleus, putamen, and claustrum. In Wistar rats, the CA3, CA1, somatosensory cortex, entorhinal cortex, piriform cortex, reticular nucleus, amygdala, and laterodorsal nucleus exhibited significant differences. Comparing GAERS and Wistar rats, a statistically significant difference was observed for both sides of CA1. In both groups, the staining was prominent ipsilaterally, except for the claustrum in GAERS rats. However, the motor cortex remained unaffected in both groups. Neurodegenerative changes were not associated with the severity of seizures in both groups following the intra-amygdaloid kainic acid administration. CONCLUSION: This study demonstrates that CA1 is the only region exhibiting a statistically significant difference between Wistar and GAERS rats.

Dopamine acting at D1-like, D2-like and α1-adrenergic receptors differentially modulates theta and gamma oscillatory activity in primary motor cortex.

The loss of dopamine (DA) in Parkinson's is accompanied by the emergence of exaggerated theta and beta frequency neuronal oscillatory activity in the primary motor cortex (M1) and basal ganglia. DA replacement therapy or deep brain stimulation reduces the power of these oscillations and this is coincident with an improvement in motor performance implying a causal relationship. Here we provide in vitro evidence for the differential modulation of theta and gamma activity in M1 by DA acting at receptors exhibiting conventional and non-conventional DA pharmacology. Recording local field potentials in deep layer V of rat M1, co-application of carbachol (CCh, 5 µM) and kainic acid (KA, 150 nM) elicited simultaneous oscillations at a frequency of 6.49 ± 0.18 Hz (theta, n = 84) and 34.97 ± 0.39 Hz (gamma, n = 84). Bath application of DA resulted in a decrease in gamma power with no change in theta power. However, application of either the D1-like receptor agonist SKF38393 or the D2-like agonist quinpirole increased the power of both theta and gamma suggesting that the DA-mediated inhibition of oscillatory power is by action at other sites other than classical DA receptors. Application of amphetamine, which promotes endogenous amine neurotransmitter release, or the adrenergic α1-selective agonist phenylephrine mimicked the action of DA and reduced gamma power, a result unaffected by prior co-application of D1 and D2 receptor antagonists SCH23390 and sulpiride. Finally, application of the α1-adrenergic receptor antagonist prazosin blocked the action of DA on gamma power suggestive of interaction between α1 and DA receptors. These results show that DA mediates complex actions acting at dopamine D1-like and D2-like receptors, α1 adrenergic receptors and possibly DA/α1 heteromultimeric receptors to differentially modulate theta and gamma activity in M1.

Glutamic acid decarboxylase isoform distribution in transgenic mouse septum: an anti-GFP immunofluorescence study.

The septum is a basal forebrain region located between the lateral ventricles in rodents. It consists of lateral and medial divisions. Medial septal projections regulate hippocampal theta rhythm whereas lateral septal projections are involved in processes such as affective functions, memory formation, and behavioral responses. Gamma-aminobutyric acidergic neurons of the septal region possess the 65 and 67 isoforms of the enzyme glutamic acid decarboxylase. Although data on the glutamic acid decarboxylase isoform distribution in the septal region generally appears to indicate glutamic acid decarboxylase 67 dominance, different studies have given inconsistent results in this regard. The aim of this study was therefore to obtain information on the distributions of both of these glutamic acid decarboxylase isoforms in the septal region in transgenic mice. Two animal groups of glutamic acid decarboxylase-green fluorescent protein knock-in transgenic mice were utilized in the experiment. Brain sections from the region were taken for anti-green fluorescent protein immunohistochemistry in order to obtain estimated quantitative data on the number of gamma-aminobutyric acidergic neurons. Following the immunohistochemical procedures, the mean numbers of labeled cells in the lateral and medial septal nuclei were obtained for the two isoform groups. Statistical analysis yielded significant results which indicated that the 65 isoform of glutamic acid decarboxylase predominates in both lateral and medial septal nuclei (unpaired two-tailed t-test p < 0.0001 for LS, p < 0.01 for MS). This study is the first to reveal the dominance of glutamic acid decarboxylase isoform 65 in the septal region in glutamic acid decarboxylase-green fluorescent protein transgenic mice.

Topical glucocorticoid reduces the topical decongestant-induced histologic changes in an animal model nasal mucosa.

OBJECTIVES/HYPOTHESIS: To investigate the histologic consequences of simultaneous nasal glucocorticosteroid and xylometazoline HCl administration in the rabbit nasal mucosa. STUDY DESIGN: Prospective randomized study. METHODS: Twenty New Zealand male rabbits were randomly placed into three groups: group I, control (n = 6); group II, xylometazoline HCl (n = 8); or group III, xylometazoline HCl-fluticasone furoate (n = 6). Group I received no treatment. Groups II and III received two intranasal puffs of xylometazoline HCl 0.5 mg/mL twice daily or two puffs of xylometazoline HCl 0.5 mg/mL twice daily plus one puff of 27.5 µg fluticasone furoate twice daily to each nostril (110 µg), respectively. At the end of 3 weeks, the rabbits were sacrificed. The mucosa of the nasal cavities was excised. Specimen sections (5 µm) were stained with hematoxylin and eosin, mucicarmine, and Gomori one-step trichrome and were examined under a light microscope. The presence of edema, congestion, inflammatory cell infiltration, nasociliary loss, epithelial and nerve-ending degeneration, and goblet cell increase were evaluated semiquantitatively (grades 0-3). RESULTS: Statistically significant differences were detected between groups II and III in terms of edema, congestion, inflammatory cell infiltration, nasociliary loss, and epithelial degeneration (P = .006, P = .049, P = .015, P = .014, and P = .049, respectively). Nerve-ending degeneration, goblet cell increase, and quantitative goblet and neutrophil cell counts did not yield statistically significant differences between groups II and III (P = .137, P = .580, P = .770, and P = .616, respectively). CONCLUSIONS: The combined simultaneous intranasal administration of xylometazoline HCl and fluticasone furoate appears to be beneficial in minimizing the long-term usage-associated congestion, edema, inflammatory cell infiltration, epithelial degeneration, and nasociliary loss in the rabbit model nasal mucosa.

Depolarisation and suppression of burst firing activity in the mouse subthalamic nucleus by dopamine D1/D5 receptor activation of a cyclic-nucleotide gated non-specific cation conductance.

Neuronal burst firing in the subthalamic nucleus (STN) is one of the hallmarks of dopamine depletion in Parkinson's disease. Here, we have determined the postsynaptic effects of dopamine in the STN and the functional consequences of dopamine receptor modulation on burst firing in vitro. STN cells displayed regular spiking activity at a rate of 7.9+/-0.5 Hz. Application of dopamine (30 microM) induced membrane depolarisations accompanied by an increase in firing rate of mean 12.0+/-0.6 Hz in all 69 cells. The dopamine effect was mimicked by the dopamine D1/D5 receptor agonist SKF38393 (10 microM, 17 cells) and the dopamine D2-like receptor agonist quinpirole (10 microM, 35 cells), partly reduced by D1/D5 antagonist SCH23390 (2 microM, seven cells), but unaffected by the D2 antagonists sulpiride (10 microM, seven cells) or eticlopride (10 microM, six cells). Using voltage ramps, dopamine induced an inward current of 69+/-9.4 pA at a holding potential of -60 mV (n=17). This current was accompanied by an increase in input conductance of 1.55+/-0.35 nS which reversed at -30.6+/-2.3 mV, an effect mimicked by SKF38393 (10 microM, nine cells). Similar responses were observed when measuring instantaneous current evoked by voltage steps and in the presence of the I(h) blocker, ZD7288, indicating effects independent of I(h). The increase in conductance was blocked by SCH23390 (2 microM, n=4), mimicked by the activator of adenylyl cyclase forskolin (10 microM, n=7) and blocked by H-89, an inhibitor of cyclic AMP dependent protein kinase A (10 microM, n=6). These results indicate that the dopamine depolarisation is in part mediated by D1/D5 receptor mediated activation of a cyclic-nucleotide gated (CNG) non-specific cation conductance. This conductance contributes to the membrane depolarisation that changes STN neuronal bursting to more regular activity by significantly increasing burst duration and number of spikes per burst.

The diameters of common carotid artery and its branches in newborns.

The common carotid artery (CCA) bifurcation is of clinical importance due to its vascular access site for intravascular intervention. Additionally, it is also one of the most common sites of atherosclerotic plaque formation. There are numerous studies on the diameters of CCA, internal carotid artery (ICA), and external carotid artery (ECA) in adults, but few studies on newborns. Cadaver and angiographic studies have shown dimensional variations in the carotid arteries within/between individuals and also between different sexes. It is well known that the initial lesions of atherosclerosis begin very early in fetal life. Therefore, it is important to know the anatomical details of the CCA and its branches. In the present study, the neck regions of 20 (11 males and 9 females) fixed newborn cadavers were dissected. The CCAs were cut below the bulb of the carotid bifurcation further; ICA and ECA were cut above the bulb of the carotid bifurcation. The internal diameters of the CCA, ICA, and ECA were measured using a light microscopy. ECA/CCA, ICA/CCA, ICA/ECA ratios, and outflow to inflow area ratio were calculated. The mean outflow to inflow area ratio was 1.14+/-0.28. Our results highly correlated with the defined optimal ratio (1.15). The ECA/CCA, ICA/CCA, and ICA/ECA ratios were 0.78+/-0.12, 0.71+/-0.13, and 0.93+/-0.16, respectively. There were no statistically significant differences between male and female and also between right and left sides. These findings are of importance in understanding the anatomy of carotid artery during newborn period.

Attitudes of Turkish anatomists toward cadaver donation.

There is an insufficient number of cadavers in anatomy education in Turkey. This is because of decreased number of unclaimed bodies and very few cadaver donations. Increasing the number of cadaver donation is one of the probable solutions. Although anatomists encourage people to donate bodies, the attitudes of anatomists toward donating their own bodies for dissection is not well known. In this study, the attitudes of Turkish anatomists toward cadaver donation were evaluated. The questionnaires were sent to the anatomists in Turkey by mail and E-mail. Eighty-three anatomists replied to the questionnaire. The main solutions proposed for cadaver insufficiency included increasing the supply of unclaimed bodies (77.1%) and increasing body donation (78.3%). Further, 51.8% of the respondents thought that increasing body donation was a long-term solution. The general belief (83.1%) was that a campaign would help to increase body donation and 47% of respondents were willing to participate in such a campaign. Of the 83 anatomists, 20.5% of the respondents donated their organs and 49.4% were planning to donate them. Further, 15.7% were planning to donate their bodies; however, 63.9% did not consider donating. The main reasons of the respondents to object the donation were: to be dissected by a colleague (15.7%), the unacceptability of donation by family (26.5%), psychological reasons (43.4%), the anxiety of disrespectful behavior to cadavers (26.5%), and religious beliefs (3.6%). Although the majority of the respondents objected to donating their bodies due to psychological reasons, body donation was proposed as the main solution of cadaver insufficiency.

Cerebellar connections to the rostral reticular nucleus of the thalamus in the rat.

We studied the cerebellar connections to the reticular nucleus thalamus (RNT) by means of retrograde axonal transport of horseradish peroxidase (HRP) in the rat. Specific HRP pressure injections to the rostral RNT (1.6-1.8 mm caudal to bregma) resulted in retrograde labelling of neurones in the cerebellar nuclei. The rostral RNT showed specific topographical organization of its cerebellar connections. Microinjections into the rostral RNT, 1.6 mm caudal to bregma, produced numerous HRP-labelled neurones within the anterior interposed (emboliform nucleus) and scarce HRP-labelled neurones within the lateral (dentate nucleus) cerebellar nuclei, whereas injections into the rostral RNT, 1.8 mm caudal to bregma, produced numerous HRP-labelled neurones within the posterior interposed (globose nucleus) and scarce lightly HRP-labelled neurones within the lateral (dentate nucleus) cerebellar nuclei. Cerebellar connections with the rostral RNT were exclusively ipsilateral to the injection site. No HRP-labelled cells were detected in the medial (fastigial nucleus) cerebellar nucleus. The cerebellar connections reach the RNT via the superior cerebellar peduncle. By contrast, HRP injections into the anterior, posterior interposed and lateral cerebellar nuclei produced no labelled cells within the RNT. This study demonstrates the existence of direct cerebello-RNT but not RNT-cerebellar connections. The presence of the cerebello-RNT connections introduces a new route through which the cerebellum may influence RNT and thus cerebral cortical activity.