Ibotenic Acid Research Articles

Simultaneous determination of γ-hydroxybutyric acid, ibotenic acid and psilocybin in saliva samples by capillary electrophoresis coupled with a contactless conductivity detector

The aim of the study was to develop a methodology for the determination of γ-hydroxybutyric acid (GHB), ibotenic acid (IBO) and psilocybin (PY) abuse in human saliva.

The effects of NBM- lesion on synaptic plasticity in rats

The nucleus basalis magnocellularis (NBM) is a major source of cholinergic projections to the neocortex that is vulnerable to degeneration in Alzheimer's disease. Despite numerous anatomical, pharmacological, behavioral, and physiological investigations of NBM, there is no in vivo study of its effects on short- or long-term synaptic plasticity. Hence, this study was devoted to the assessment of the effects of bilateral lesion of the NBM on synaptic plasticity in the dentate gyrus of the hippocampus using electrophysiological techniques. For this purpose, twenty-five male Wistar rats were randomly allocated into the three Control, Sham, and NBM-lesioned groups. Lesion was made via bilateral injections of 5µg/µl ibotenic acid. After twenty-one days, the input–output functions, paired-pulse facilitation/inhibition, and long-term potentiation (LTP) were evaluated in the dentate gyrus while the perforant pathway was stimulated. NBM lesion was found to attenuate the basal synaptic responsiveness, paired-pulse responses, and LTP in the rats’ dentate gyrus, indicating that lesions of this cholinergic nucleus affects both short- and long-term neural plasticity in the dentate gyrus although NBM does not send direct cholinergic projections to the hippocampus.

Basolateral amygdalar D2 receptor activation is required for the companions-exerted suppressive effect on the cocaine conditioning

The presence of companions renders decreases in cocaine-stimulated dopamine release in the nucleus accumbens and cocaine-induced conditioned place preference (CPP) magnitude. Limbic systems are widely believed to underlie the modulation of accumbal dopamine release and cocaine conditioning. Thus, this study aimed to assess whether intact basolateral nucleus of amygdala (BLA), dorsal hippocampus (DH), and dorsolateral striatum (DLS) is required for the companions-exerted suppressive effect on the cocaine-induced CPP. Three cage mates, serving as companions, were arranged to house with the experimental mice in the cocaine conditioning compartment throughout the cocaine conditioning sessions. Approximately 1week before the conditioning procedure, intracranial ibotenic acid infusions were done in an attempt to cause excitotoxic lesions targeting bilateral BLA, DH and DLS. Albeit their BLA, DH, and DLS lesions, the lesioned mice exhibited comparable cocaine-induced CPP magnitudes compared to the intact and sham lesion controls. Bilateral BLA, but not DH or DLS, lesions abolished the companions-exerted suppressive effect on the cocaine-induced CPP. Intact mice receiving intra-BLA infusion of raclopride, a selective D2 antagonist, 30min prior to the cocaine conditioning did not exhibit the companions-exerted suppressive effect on the cocaine-induced CPP. Intra-BLA infusion of Sch23390, a selective D1 antagonist, did not affect the companions-exerted suppressive effect on the CPP. These results, taken together, prompt us to conclude that the intactness of BLA is required for the companions-exerted suppressive effect on the cocaine-induced CPP. Importantly, activation of D2 receptor in the BLA is required for such suppressive effect on the CPP.

REM sleep disorder following general anesthesia in rats

Postoperative sleep disorders, particularly the REM sleep disorder, may have a significant deleterious impact on postoperative outcomes and may contribute to the genesis of certain delayed postoperative complications.We have followed the effect of distinct anesthesia regimens (ketamine/diazepam vs. pentobarbital) over 6days following the induction of a stable anesthetized state in adult male Wistar rats, chronically instrumented for sleep recording. In order to compare the effect of both anesthetics in the physiological controls vs. the rats with impaired pedunculopontine tegmental nucleus (PPT) cholinergic innervation, during the operative procedure for the implantation of EEG and EMG electrodes, the bilateral PPT lesion was conducted using ibotenic acid (IBO). We have followed in particular post-anesthesia REM sleep.Our results show the distinct EEG microstructure of the motor cortex during the different stable anesthetized states, and their distinct impact on post-anesthesia REM sleep. In contrast to pentobarbital anesthesia, the ketamine/diazepam anesthesia potentiated the long-lasting post-anesthesia REM statewith higher muscle tone (REM1) vs. REM state with atonia (REM2). Whereas both anesthesias prolonged the post-anesthesia REM sleep duration, the long-term prolongation of the REM1 state was demonstrated only after the ketamine/diazepam anesthesia, first due to the increased number of REM1 episodes, and then due to the prolonged REM1 episodes duration. On the other hand, whereas both anesthetic regimens abolished the prolonged post-anesthesia REM/REM1 sleep and the EEG microstructure disorder during REM sleep, only the pentobarbital abolished the increased NREM/REM/NREM transitions, caused by the PPT lesion. In addition, in the PPT lesioned rats, the ketamine/diazepam anesthesia decreased the Wake/NREM/Wake transitions while the pentobarbital anesthesia decreased the Wake/REM/Wake transitions.Our present study suggests pentobarbital anesthesia as being highly beneficial for post-anesthesia REM sleep in the physiological condition as well as during PPT cholinergic neuropathology.

Central and peripheral administrations of levothyroxine improved memory performance and amplified brain electrical activity in the rat model of Alzheimer's disease

Alzheimer's disease (AD) is associated with cognitive impairments and a decline in the spontaneous neuronal discharge. In the current study, we evaluated the effect of subcutaneous (S.C.) and intrahippocampal (I.H.) administrations of levothyroxine (LT-4) on the passive avoidance and spatial memory, as well as electrophysiological activity in an animal model of AD. One hundred-sixty male Wistar rats were divided into two main groups. The S.C. group included two Sham and four AD (vehicle or L-T4 25, 50 & 100μg/kg); and the I.H. had consisted of two Sham and two AD (vehicle or L-T4 10μg/kg) subgroups. To make an animal model of AD, amyloid beta (Aβ) plus ibotenic acid (Ibo) were injected I.H. Rats were treated with L-T4 and/or normal saline for ten days. Passive avoidance and spatial memory were evaluated in shuttle box and Morris water maze, respectively. Neuronal single unit recording was assessed from hippocampal dentate gyrus (DG). Results showed that the mean latency time (s) increased significantly (p<0.001) in AD animals and decreased significantly in both S.C. and I.H. L-T4 injected AD animals, compared with the AD group (p<0.001). The percentage of total time that animals spent in goal quarter and the step through latency decreased significantly in AD rats (p<0.001) and increased significantly in both S.C. and I.H. L-T4 injected AD animals in comparison with the AD group (p<0.01, p<0.001). Data showed that the average number of spikes/bin significantly decreased in the AD group (p<0.001). The S.C. and I.H. L-T4 injections in AD rats significantly increased the spike rate in comparison to the AD group (p<0.001).In conclusion, both S.C. and I.H. injections of L-T4 alleviated memory deficits and spontaneous neuronal activity in Aβ-induced AD rats. Also, I.H. microinjection of L-T4 had more beneficial effects on memory and neuronal electrophysiological activity in comparison to S.C. administration.

Intranasal Oncolytic Virotherapy with CXCR4-Enhanced Stem Cells Extends Survival in Mouse Model of Glioma.

SummaryThe challenges to effective drug delivery to brain tumors are twofold: (1) there is a lack of non-invasive methods of local delivery and (2) the blood-brain barrier limits systemic delivery. Intranasal delivery of therapeutics to the brain overcomes both challenges. In mouse model of malignant glioma, we observed that a small fraction of intranasally delivered neural stem cells (NSCs) can migrate to the brain tumor site. Here, we demonstrate that hypoxic preconditioning or overexpression of CXCR4 significantly enhances the tumor-targeting ability of NSCs, but without altering their phenotype only in genetically modified NSCs. Modified NSCs deliver oncolytic virus to glioma more efficiently and extend survival of experimental animals in the context of radiotherapy. Our findings indicate that intranasal delivery of stem cell-based therapeutics could be optimized for future clinical applications, and allow for safe and repeated administration of biological therapies to brain tumors and other CNS disorders.

Effects of lesions of the subthalamic nucleus/zona incerta area and dorsomedial striatum on attentional set-shifting in the rat

Patients with Parkinson’s disease (PD) show cognitive impairments, including difficulty in shifting attention between perceptual dimensions of complex stimuli. Inactivation of the subthalamic nucleus (STN) has been shown to be effective in ameliorating the motor abnormalities associated with striatal dopamine (DA) depletion, but it is possible that STN inactivation might result in additional, perhaps attentional, deficits. This study examined the effects of: DA depletion from the dorsomedial striatum (DMS); lesions of the STN area; and the effects of the two lesions together, on the ability to shift attentional set in the rat.In a single session, rats performed the intradimensional/extradimensional (ID/ED) test of attentional set-shifting. This comprises a series of seven, two-choice discriminations, including acquisitions of novel discriminations in which the relevant stimulus is either in the currently attended dimension (ID) or the currently unattended dimension (ED shift) and reversals (REVs) following each acquisition stage.Bilateral lesions were made by injection of 6-hydroxydopamine (6-OHDA) into the DMS, resulting in a selective impairment in reversal learning. Large bilateral ibotenic acid lesions centered on the STN resulted in an increase in trials to criterion in the initial stages, but learning rate improved within the session. There was no evidence of a ‘cost’ of set-shifting – the ED stage was completed in fewer trials than the ID stage – and neither was there a cost of reversal learning. Strikingly, combined lesions of both regions did not resemble the effects of either lesion alone and resulted in no apparent deficits.

Icariin, a major constituent from Epimedium brevicornum, attenuates ibotenic acid-induced excitotoxicity in rat hippocampus

Excitotoxicity is one of the most extensively studied causes of neuronal death and plays an important role in Alzheimer’s disease (AD). Icariin is a flavonoid component of a traditional Chinese medicine reported to possess a broad spectrum of pharmacological effects. The present study was designed to investigate the effects of icariin against learning and memory impairment induced by excitotoxicity. Here, we demonstrated that rats receiving intracerebroventricular injection of excitatory neurotoxin ibotenic acid exhibited impaired learning and memory. Oral administration of icariin at doses of 20 and 40mg/kg rescued behavioral performance and protected against neurotoxicity in rat hippocampus by suppressing ibotenic acid induced pro-apoptosis. Furthermore, Western blott of hippocampal specimens revealed that icariin up-regulated the expression of calbindin-D28k protein following ibotenic acid administration. Additionally, icariin inhibited mitogen-activated protein kinase (MAPK) family phosphorylation and nuclear factor kappa B (NF-κB) signaling, implicating the MAPK signaling and NF-κB signaling pathways were involved in the mechanism underlying icariin-mediated neuroprotection against ibotenic acid-induced excitotoxicity. These data suggested that icariin could be a potential agent for treatment of excitotoxicity-related diseases, including AD.

Effects of acupuncture at HT7 on glucose metabolism in a rat model of Alzheimer's disease: an 18F-FDG-PET study.

ObjectiveTo explore the effects of acupuncture at HT7 on different cerebral regions in a rat model of Alzheimer's disease (AD) with the application of 18F-2-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET).MethodsSixty Wistar rats were included after undergoing a Y-maze electric sensitivity test. Ten rats were used as a healthy control group. The remaining 50 rats were injected stereotaxically with ibotenic acid into the right nucleus basalis magnocellularis and injected intraperitoneally with D-galactose. AD was successfully modelled in 36 rats, which were randomly divided into three groups (n=12 each): the AD group, which remained untreated; the AD+HT7 group, which received 20 sessions of acupuncture at HT7 over 1 month; and the AD+Sham group, which received acupuncture at a distant non-acupuncture point. Total reaction time (TRT) was measured by Y-maze and 18F-FDG-PET scans were conducted on day 1 and 30. PET images were processed with Statistical Parametric Mapping 8.0.ResultsPre-treatment, TRT was greater in all AD groups versus controls (mean±SD 24.10±2.48 vs 41.34±5.00 s). Post-treatment, TRT was shortened in AD+HT7 versus AD+Sham and AD groups (p<0.0001, two-way analysis of variance). Glucose metabolic activity in the hippocampus, thalamus, hypothalamus, frontal lobe, and temporal lobe was decreased in AD rats compared with healthy controls and relatively elevated after HT7 acupuncture. Compared with sham acupuncture, HT7 needling had a greater positive influence on brain glucose metabolism.ConclusionsNeedling at HT7 can improve memory ability and cerebral glucose metabolic activity of the hippocampus, thalamus, hypothalamus, and frontal/temporal lobes in an AD rat model.

Posterodorsal Medial Amygdala Mediates Tail-Pinch Induced Food Intake in Female Rats.

Comfort eating during periods of stress is a common phenomenon observed in both animals and humans. However, the underlying mechanisms of stress‐induced food intake remain elusive. The amygdala plays a central role in higher‐order emotional processing and the posterodorsal subnucleus of the medial amygdala (MePD), in particular, is involved in food intake. Extra‐hypothalamic corticotrophin‐releasing factor (CRF) is well recognised for mediating behavioural responses to stress. To explore the possible role of amygdala CRF receptor activation in stress‐induced food intake, we evaluated whether a stressor such as tail‐pinch, which reliably induces food intake, would fail to do so in animals bearing bilateral neurotoxic lesions of the MePD. Our results showed that ibotenic acid induced lesions of the MePD markedly reduced tail‐pinch induced food intake in ovariectomised, 17β‐oestradiol replaced rats. In addition, intra‐MePD (right side only) administration of CRF (0.002 or 0.02 ng) via chronically implanted cannulae resulted in a dose‐dependent increase in food intake, although higher doses of 0.2 and 2 ng CRF had less effect, producing a bell shaped curve. Furthermore, intra‐MePD (bilateral) administration of the CRF receptor antagonist, astressin (0.3 μg per side) effectively blocked tail‐pinch induced food intake. These data suggest that the MePD is involved in stress‐induced food intake and that the amygdala CRF system may be a mediator of comfort eating.

Intrahippocampal Administration of Ibotenic Acid Induced Cholinergic Dysfunction via NR2A/NR2B Expression: Implications of Resveratrol against Alzheimer Disease Pathophysiology.

Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression toward Alzheimer's disease (AD) pathology. Resveratrol (RSV), a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age-associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO) in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5 μg/μl) lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly α7-nAChR with increased m1AChR. RSV administration (20 mg/kg body weight, i.p.) significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility, and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the hippocampal pyramidal layer thickness and live neurons in IBO induced rats, with slight pathological changes in the entorhinal cortex (EC) of rat brain, which was prevented on RSV administration. Our study thus concludes that RSV administration significantly ameliorated the deleterious effects in the IBO lesioned rat model for AD by alleviating cholinergic pathways, reducing oxidative stress and thereby improving spatial memory.

Unraveling a new circuitry for sleep regulation in Parkinson's disease

Sleep disturbances are among the most disabling non-motor symptoms in Parkinson's disease. The pedunculopontine tegmental nucleus and basal ganglia are likely involved in these dysfunctions, as they are affected by neurodegeneration in Parkinson's disease and have a role in sleep regulation. To investigate this, we promoted a lesion in the pedunculopontine tegmental nucleus or substantia nigra pars compacta of male rats, followed by 24 h of REM sleep deprivation. Then, we administrated a dopaminergic D2 receptor agonist, antagonist or vehicle directly in the striatum. After a period of 24 h of sleep-wake recording, we observed that the ibotenic acid infusion in the pedunculopontine tegmental nucleus blocked the so-called sleep rebound effect mediated by REM sleep deprivation, which was reversed by striatal D2 receptors activation. Rotenone infusion in the substantia nigra pars compacta also blocked the sleep rebound, however, striatal D2 receptors activation did not reverse it. In addition, rotenone administration decreased the time spent in NREM sleep, which was corroborated by positive correlations between dopamine levels in both substantia nigra pars compacta and striatum and the time spent in NREM sleep. These findings suggest a new circuitry for sleep regulation in Parkinson's disease, involving the triad composed by pedunculopontine nucleus, substantia nigra pars compacta and striatum, evidencing a potential therapeutic target for the sleep disturbances associated to this pathology.

Catching flies with Amanita muscaria: traditional recipes from Slovenia and their efficacy in the extraction of ibotenic acid

Ethnopharmacological relevanceFly control is necessary for maintaining good hygiene on farms. Because organic farmers are skeptical about chemical pesticides, alternative fly control remedies are being considered. Amanita muscaria is a widespread fungus that contains ibotenic acid and muscimol. This fungus has been used to catch flies for centuries, but traditional recipes are poorly described, documented and characterized. Aim of the studyThe aim of the present study was to collect the traditional methods for preparing A. muscaria for catching flies in Karst and Gorjanci and to investigate the influence of different traditional methods on the release of ibotenic acid and muscimol from the fungal material. Materials and methodsThe research was conducted in villages in Karst and in the foothills of Gorjanci, Slovenia. Data regarding the traditional recipes of A. muscaria for catching flies were collected through structured interviews with 31 people in Karst and 28 in Gorjanci. Eight preparations were prepared based on traditional methods, and the amount of ibotenic acid and muscimol released from the fungal material at five different time points (0.5, 1, 2, 3 and 24h) was determined by high-performance liquid chromatography (HPLC). ResultsDetailed descriptions of preparations used for catching flies were obtained from three informants in Karst, who were originally from other parts of Slovenia, and 13 informants in the foothills of Gorjanci. However, there were no reports regarding current usage. A total of 9 different methods were collected. Some methods were simple and included soaking in milk or water or dripping a little milk onto the mushroom. Others were more complex and included a combination of heat or mechanical processing and soaking in milk or water. For all preparations, the release of ibotenic acid was time-dependent, with the extracted amount increasing over time. Although milk was used more often than water in the traditional recipes, the release of both substances was not dependent on the solvent used. Fungal material that was exclusively soaked in water or milk released the smallest amount of ibotenic acid and muscimol at each time point. Additional heat and mechanical processing led to faster release of ibotenic acid and muscimol from the fungal material. ConclusionsThe tradition of using A. muscaria for catching flies was present in Gorjanci but not in Karst. The methods used to prepare the fungal material vary, and these differences are reflected in the release profile of ibotenic acid.

Lesions of a higher auditory brain area during a sensorimotor period do not impair birdsong learning &amp;nbsp;

One important function of the nervous system is to form and retrieve memories to direct behavior. A prime example of memorization occurs in songbirds when they imitate the songs of another bird heard early in life. Although many brain areas required for song learning have been identified, their separate roles in memory formation and retrieval remain unclear. In juvenile male zebra finches, we test the role of a higher auditory cortical area in memory retrieval. The Caudal Medial Nidopallium (NCM) has previously been shown to be necessary for song memory acquisition and is thus a likely location for holding the memory of tutor song necessary for learning. We extensively exposed young birds to tutor song after which we performed large bilateral lesions in NCM using injection of ibotenic acid. We observe successful song copying in lesioned animals, comparable to song behavior in untreated control birds. Our results show that intact NCM is not required to guide vocal learning based on a previously formed song memory.

Thalamic mediation of hypoxic respiratory depression in lambs.

Immaturity of respiratory controllers in preterm infants dispose to recurrent apnea and oxygen deprivation. Accompanying reductions in brain oxygen tensions evoke respiratory depression, potentially exacerbating hypoxemia. Central respiratory depression during moderate hypoxia is revealed in the ventilatory decline following initial augmentation. This study determined whether the thalamic parafascicular nuclear (Pf) complex involved in adult nociception and sensorimotor regulation (Bentivoglio M, Balerecia G, Kruger L. Prog Brain Res 87: 53-80, 1991) also becomes a postnatal controller of hypoxic ventilatory decline. Respiratory responses to moderate isocapnic hypoxia were studied in conscious lambs. Hypoxic ventilatory decline was compared with peak augmentation. Pf and/or adjacent thalamic structures were destroyed by the neuron-specific toxin ibotenic acid (IB). IB lesions involving the thalamic Pf abolished hypoxic ventilatory decline. Lesions of adjacent thalamic nuclei that spared Pf and control injections of vehicle failed to blunt hypoxic respiratory depression. Our findings reveal that the thalamic Pf region is a critical controller of hypoxic ventilatory depression and thus a key target for exploring molecular concomitants of forebrain pathways regulating hypoxic ventilatory depression in early development.

Neonatal ventral hippocampus lesion changes nuclear restricted protein/brain (NRP/B) expression in hippocampus, cortex and striatum in developmental periods of rats

Schizophrenia is conceptualized as a neurodevelopmental disorder in which developmental alterations in immature brain systems are not clear. Rats with neonatal ventral hippocampal lesions (NVHL) can exhibit schizophrenia-like behaviors, and these rats have been widely used to study the developmental mechanisms of schizophrenia. The nuclear restricted protein/brain (NRP/B) is a nuclear matrix protein that is critical for the normal development of the neuronal system. This study assessed the effect of NVHL induced by the administration of ibotenic acid on the protein expression of NRP/B in the hippocampus, cortex and striatum in pre- and post-pubertal rats. The expressions of NeuN in various developmental periods were assessed accordingly. Sprague–Dawley rat pups were administered ibotenic acid at postnatal day (PD) 7. Western blotting and an immunofluorescence staining analysis showed that the expression of NRP/B was significantly decreased in the hippocampus, cortex and striatum of the NVHL rats at PD14, 28 and 42. The expressions of NeuN were decreased accordingly. In vitro experiment showed the NRP/B knockdown can decrease the Tuj1 expression in cultured cortical neurons. The data suggest that NVHL induces a change in NRP/B expression that affects neurons in the developmental period.

Enzyme-luminescence method: Tool for real-time monitoring of natural neurotoxins in vitro and l-glutamate release from primary cortical neurons

Novel enzyme-luminescence method is used for the rapid and sensitive in vitro detection of natural neurotoxins (e.g., shellfish and mushroom toxins) using model brain cells. Paralytic shellfish poisons gonyautoxins (e.g., GTX2,3 and GTX1,4) were detected at 1nM level by their inhibition of glutamate release from C6 glioma cells upon drug stimulation (IC50: GTX2,3=30nM and GTX1,4=8nM). Activation of glutamate release from C6 cells by ibotenic acid (a mushroom toxin) was also evaluated (EC50=10nM). The method was tested for real-time detection of glutamate release from primary rat cortical neurons. Dose-dependent effects of KCl (0–200mM) and NMDA on glutamate release from primary cortical neurons were studied. The effects of different culture conditions on K+-depolarization-induced glutamate release were also investigated. The method may be applicable to screening of drugs and toxins, and finding glutamatergic neurons in brain slices without in situ staining.

Cholinergic excitation from the pedunculopontine tegmental nucleus to the dentate nucleus in the rat

In spite of the existence of pedunculopontine tegmental nucleus (PPTg) projections to cerebellar nuclei, their nature and functional role is unknown. These fibers may play a crucial role in postural control and may be involved in the beneficial effects induced by deep-brain stimulation (DBS) of brainstem structures in motor disorders. We investigated the effects of PPTg microstimulation on single-unit activity of dentate, fastigial and interpositus nuclei. The effects of PPTg stimulation were also studied in rats whose PPTg neurons were destroyed by ibotenic acid and subsequently subjected to iontophoretically applied cholinergic antagonists. The main response recorded in cerebellar nuclei was a short-latency (1.5–2ms) and brief (13–15ms) orthodromic activation. The dentate nucleus was the most responsive to PPTg stimulation. The destruction of PPTg cells reduced the occurrence of PPTg-evoked activation of dentate neurons, suggesting that the effect was due to stimulation of cell bodies and not due to fibers passing through or close to the PPTg. Application of cholinergic antagonists reduced or eliminated the PPTg-evoked response recorded in the dentate nucleus. The results show that excitation is exerted by the PPTg on the cerebellar nuclei, in particular on the dentate nucleus. Taken together with the reduction of nicotinamide adenine dinucleotide phosphate-diaphorase-positive neurons in lesioned animals, the iontophoretic experiments suggest that the activation of dentate neurons is due to cholinergic fibers. These data help to explain the effects of DBS of the PPTg on axial motor disabilities in neurodegenerative disorders.

Cortical regulation of striatal projection neurons and interneurons in a Parkinson's disease rat model.

Striatal neurons can be either projection neurons or interneurons, with each type exhibiting distinct susceptibility to various types of brain damage. In this study, 6-hydroxydopamine was injected into the right medial forebrain bundle to induce dopamine depletion, and/or ibotenic acid was injected into the M1 cortex to induce motor cortex lesions. Immunohistochemistry and western blot assay showed that dopaminergic depletion results in significant loss of striatal projection neurons marked by dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein, molecular weight 32 kDa, calbindin, and μ-opioid receptor, while cortical lesions reversed these pathological changes. After dopaminergic deletion, the number of neuropeptide Y-positive striatal interneurons markedly increased, which was also inhibited by cortical lesioning. No noticeable change in the number of parvalbumin-positive interneurons was found in 6-hydroxydopamine-treated rats. Striatal projection neurons and interneurons show different susceptibility to dopaminergic depletion. Further, cortical lesions inhibit striatal dysfunction and damage induced by 6-hydroxydopamine, which provides a new possibility for clinical treatment of Parkinson's disease.

Cerebral Glucose Metabolism Assessment in Rat Models of Alzheimer's Disease: An 18F-FDG-PET Study.

This study was designed to detect the brain glucose metabolism in rat models of Alzheimer's disease (AD) by the application of (18)F-2-fluoro-deoxy-d-glucose positron emission tomography ((18)F-FDG-PET) and to provide new insights for the early detection of AD. Forty Wistar rats were randomly divided into 2 groups. Fifteen sham-operated rats were used as a control group. The remaining rats as a premodel group were intracerebroventricularly injected with ibotenic acid and were intraperitoneally injected with d-galactose, of which 15 rats were included as the experimental group. The above-mentioned 2 groups were assigned to Y-maze test and underwent (18)F-FDG-PET scanning. Positron emission tomography images were processed with SPM 2.0. The learning and memory skills were weakened in AD rats. Besides, the glucose metabolic activity of AD rats decreased in hippolampus, hypothalamus, insular cortex, piriform cortex, striatum, cingulate gyrus, stria terminalis, and parietal lobe and increased in olfactory bulb, cerebellum, midbrain, pontine, and retrosplenial cortex compared with the control group. Dorsal thalamus had shown both enhanced and reduced glucose metabolic activity. Our data indicate that the changed glucose metabolism in cerebral regions in (18)F-FDG-PET imaging could be an important predictor for early AD.