PubMed Health⌕ Search

Biomedical subjects

Yasin Temel

Publications and source records attributed to Yasin Temel.

At least 19 recordsLinked to original sources
PubMed2026

Causal Effects Between Neurodegenerative Diseases, Metabolites, and Brain Volume.

INTRODUCTION/OBJECTIVE: Neurodegenerative diseases such as Alzheimer's disease (AD), Lewy dody dementia (LBD), and Parkinson's disease (PD) are linked to changes in brain volume. However, causal evidence on how these diseases affect brain volume and whether metabolites mediate these causal effects remains limited. METHODS: We applied mediation Mendelian randomization analysis using GWAS summary statistics. The inverse variance-weighted method was used to assess causal effects and identify potential metabolite mediators. RESULTS: The MR analyses indicated that bilateral thalamus and putamen volumes (FDR < 0.05) had causal effects on PD. AD and LBD showed causal effects on bilateral thalamus and hippocampus (FDR < 0.01), with LBD specifically showing a causal effect on bilateral putamen (FDR < 0.05). Mediation analyses revealed that AD had a genetically predicted association with Nervonoy- L-carnitine and 1-linoleoyl-2-arachidonoyl-GPC (p-value = 0.04 and 0.01, respectively). Moreover, Nervonoy-L-carnitine was suggestively negatively associated with hippocampus volume (p-value = 0.03 and 0.02, respectively). 1-linoleoyl-2-arachidonoyl-GPC exhibited a negative genetically predicted association with hippocampus volume (p-value < 0.05). Additionally, LBD showed a negative genetically predicted association on the ratio of retinol to linoleoyl-arachidonoyl- glycerol (p-value = 0.02), and a positive genetically predicted association on Nervonoy-L-- carnitine (p-value < 0.05) and 1-linoleoyl-2-arachidonoyl-GPC (p-value = 0.03). DISCUSSION: These results suggest that AD and LBD affect brain regions through causal pathways. The involvement of specific metabolites highlights potential mechanisms linking neurodegeneration to brain volume. CONCLUSION: Nervonoylcarnitine and 1-linoleoyl-2-arachidonoyl-GPC may mediate the predicted effects of AD and LBD on hippocampal volumes, while the ratio of retinol to linoleoyl-arachidonoyl- glycerol mediates only LBD.

Humans↗
PubMed2006

Protection of nigral cell death by bilateral subthalamic nucleus stimulation.

In Parkinson disease (PD), the subthalamic nucleus (STN) becomes hyperactive (disinhibited), which is reported to cause excitotoxic damage to midbrain dopaminergic neurons. Here, we examined whether silencing of the hyperactive STN by chronic bilateral deep brain stimulation (DBS) increased the survival of midbrain dopaminergic neurons in a rat model of PD. High-precision design-based stereologic examination of the total number of neurons and tyrosine tydroxylase (TH) immunoreactive neurons in the substantia nigra pars compacta revealed that STN DBS resulted in a significant survival of these neurons. These data provide the first evidence in vivo that bilateral STN DBS is useful for protecting midbrain dopaminergic neurons from cell death in PD.

Adrenergic Agents↗
PubMed2006

Motor and cognitive improvement by deep brain stimulation in a transgenic rat model of Huntington's disease.

Altered activity of the globus pallidus externus (GPe) is responsible for at least part of the cognitive and motor symptoms of Huntington's disease (HD). In this study, we tested the hypothesis that bilateral globus pallidus (GP; equivalent of GPe in primates) deep brain stimulation (DBS) improves cognitive and motor symptoms in the first transgenic rat model of HD (tgHD rats). GP DBS with clinically relevant stimulation parameters resulted in a significant improvement of cognitive dysfunction and reduced the number of choreiform movements. This data indicate that GPe DBS can be used to treat cognitive and motor dysfunction in HD.

Animals↗
PubMed2006

Behavioural changes after bilateral subthalamic stimulation in advanced Parkinson disease: a systematic review.

INTRODUCTION: The long-lasting beneficial effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on motor function have now largely been acknowledged. Whereas behavioural changes have been demonstrated in certain case reports and small case series, some authors have not observed behavioural changes at all. The extent to which these changes occur has not yet been established. The aim of the present study was to systematically analyse behavioural changes of bilateral STN DBS. MATERIALS AND METHODS: A structured Medline search was conducted using previously described methods. Studies were selected according to specific in- and exclusion criteria. Data on patients, surgical technique, outcome and complications were collected and pooled. RESULTS: In total 1,398 patients who underwent bilateral STN DBS were included. The total cumulative follow-up period was 1,480 patient-years. Cognitive problems were seen in 41%, depression in 8%, and (hypo)mania in 4% of the patients. Anxiety disorders were observed in less than 2%, and personality changes, hypersexuality, apathy, anxiety, and aggressiveness were observed in less than 0.5% of the group studied. About half of the patients did not experience behavioural changes. CONCLUSION: Caregivers should be aware of the extent of these behavioural changes and a risk/benefit evaluation should be performed for individual patients.

Adult↗
PubMed2006

Progressive deterioration of reaction time performance and choreiform symptoms in a new Huntington's disease transgenic ratmodel.

We tested the hypothesis that a recently developed transgenic rat model of Huntington's disease (tgHD rats) showed an age-and genotype-dependent change in psychomotor performance and in the frequency of choreiform movements similar to HD patients. Wild type and tgHD (homozygotic and heterozygotic) rats were behaviorally tested at an age of 15 and 20 months. Our results show that tgHD rats exhibit an age-, and genotype-dependent deterioration of the psychomotor performance and choreiform symptoms, closely mimicking the clinical time course changes of psychomotor symptoms of HD patients. These data provide further experimental evidence that the tgHD rat can be considered as a relevant animal model of HD.

Age Factors↗
PubMed2006

The subthalamic nucleus: From response selection to execution.

The involvement of the subthalamic nucleus in physiological and pathological motor behaviour has now largely been established. Clinical observations in patients suffering from Parkinson disease treated with Deep Brain Stimulation of the STN show that these patients can suffer from postoperative changes in non-motor behaviour mainly involving alterations in cognitive functions. The involvement of the STN in cognition has initially been demonstrated by non-human studies investigating the effects of STN lesions and stimulations on cognitive parameters. In the present review, we discuss the findings of these preclinical studies on cognitive parameters and outline the anatomical and functional place of the STN in the basal ganglia cognitive circuit.

Animals↗
PubMed2006

Selective striatal neuron loss and alterations in behavior correlate with impaired striatal function in Huntington's disease transgenic rats.

Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by selective striatal neuron loss and motor, cognitive and affective disturbances. The present study aimed to test the hypothesis of adult-onset neuron loss in striatum and frontal cortical layer V as well as alterations in behavior pointing to impaired striatal function in a recently developed transgenic rat model of HD (tgHD rats) exhibiting enlarged ventricles, striatal atrophy and pycnotic pyramidal cells in frontal cortical layer V. High-precision design-based stereological analysis revealed a reduced mean total number of neurons in the striatum but not in frontal cortical layer V of 12-month-old tgHD rats compared with age-matched wild-type controls. No alterations in mean total numbers of striatal neurons were found in 6-month-old animals. Testing 14-month-old animals in a choice reaction time task indicated impaired striatal function of tgHD rats compared with controls.

Animals↗
PubMed2006

Deep brain stimulation in Tourette's syndrome: two targets?

In this report, we describe the effects of bilateral thalamic stimulation in one patient and of bilateral pallidal stimulation in another patient. Both patients suffered from intractable Tourette's syndrome (TS). Any conservative treatment had failed or had been stopped because of unbearable side effects in the 2 patients. In both cases, there was no comorbidity except for associated behavioral symptoms (compulsions). Electrodes were implanted at the level of the medial part of the thalamus (centromedian nucleus, the substantia periventricularis, and the nucleus ventro-oralis internus) in one patient and in the posteroventral part of the globus pallidus internus (GPi) in the other patient. In both cases, deep brain stimulation (DBS) resulted in a substantial reduction of tics and compulsions. These data show that bilateral DBS of the thalamus as well as of the GPi can have a good effect on tics and behavioral symptoms in patients suffering from intractable TS.

Adult↗
PubMed2006

Role of the brain in the control of erection.

In contrast to the spinal control of erection, relatively little is known about the brain control. In the present review, we have outlined the role of brain structures involved in penile erection and provided a synopsis on the brain circuit of erection. Findings from both animal and human studies are discussed. Evidence suggests that the most important structures are the frontal lobe, cingulate gyrus, amygdala, thalamus and hypothalamus. Within the brain circuit of erection, the thalamus serves as a gate-controller in which all relevant information is evaluated and further processed to higher and lower centres.

Brain↗
PubMed2006

Targets for deep brain stimulation in Parkinson's disease.

The use of stimulation electrodes implanted in the brain to control severely disabling neurological and psychiatric conditions is an exciting and fast emerging area of neuroscience. An excellent example is Parkinson's disease (PD), in which tens of thousands of patients have now been implanted with stimulation electrodes. Patients with PD underwent deep brain stimulation (DBS) at the level of the thalamus, globus pallidus internus, subthalamic nucleus, pedunculopontine nucleus and prelemniscal radiation. The results of these interventions revealed that each target has its own specific stimulation-related positive and negative effects. Clinicians can choose their DBS target based on the situation of their individual PD patients. In the authors' opinion, patient-specific targeting should be preferred over disease-specific targeting. In this review, the authors give an overview of the targets that have been used for DBS in PD and discuss patient-specific targeting.

Deep Brain Stimulation↗
PubMed2005

Differential effects of subthalamic nucleus stimulation in advanced Parkinson disease on reaction time performance.

The aim of the present study was to assess the effect of bilateral subthalamic nucleus (STN) stimulation and dopaminergic medication on speed of mental processing and motor function. Thirty-nine patients suffering from advanced Parkinson disease (PD) were operated on. Motor function and reaction time (RT) performance [simple RT (SRT) and complex RT (CRT)] were evaluated under four experimental conditions with stimulation (stim) and medication (med) on and off: stim-on/med-on, stim-on/med-off, stim-off/med-off and stim-off/med-on. In the last condition, the patients received either low medication (usual dose) or high medication (suprathreshold dose). STN stimulation improved the motor performance in the SRT and CRT tasks. Furthermore, STN deep brain stimulation (DBS) also improved response preparation as shown by the significant improvement of the RT performance in the SRT task. This effect of STN DBS on the RT performance in the SRT task was greater as compared with the CRT task. This is due to the more complex information processing that is required in the CRT task as compared to the SRT task. These data suggest that treatment of STN hyperactivity by DBS improves motor function, confirming earlier reports, but has a differential effect on cognitive functions. The STN seems to be an important modulator of cognitive processing and STN DBS can differentially affect motor and associative circuits.

Activities of Daily Living↗
PubMed2005

The functional role of the subthalamic nucleus in cognitive and limbic circuits.

Once it was believed that the subthalamic nucleus (STN) was no more than a relay station serving as a "gate" for ascending basal ganglia-thalamocortical circuits. Nowadays, the STN is considered to be one of the main regulators of motor function related to the basal ganglia. The role of the STN in the regulation of associative and limbic functions related to the basal ganglia has generally received little attention. In the present review, the functional role of the STN in the control of cortico-basal ganglia-thalamocortical associative and limbic circuits is discussed. In the past 20 years the concepts about the functional role of the STN have changed dramatically: from being an inhibitory nucleus to a potent excitatory nucleus, and from being involved in hyperkinesias to hypokinesias. However, it has been demonstrated only recently, mainly by reports on the behavioral (side-) effects of STN deep brain stimulation (DBS), which is a popular surgical technique in the treatment of patients suffering from advanced Parkinson Disease (PD), that the STN is clinically involved in associative and limbic functions. These findings were confirmed by results from animal studies. Experimental studies applying STN DBS or STN lesions to investigate the neuronal mechanisms involved in these procedures found profound effects on cognitive and motivational parameters. The anatomical, electrophysiological and behavioral data presented in this review point towards a potent regulatory function of the STN in the processing of associative and limbic information towards cortical and subcortical regions. In conclusion, it can be stated that the STN has anatomically a central position within the basal ganglia thalamocortical associative and limbic circuits and is functionally a potent regulator of these pathways.

Animals↗
PubMed2005

Acute and separate modulation of motor and cognitive performance in parkinsonian rats by bilateral stimulation of the subthalamic nucleus.

The subthalamic nucleus (STN) is involved in motor and cognitive performance through its key role in the basal ganglia-thalamocortical circuits, but how these different modalities (motor and cognition) are controlled (similar vs. dissimilar) has not yet been elucidated. In the present study, the effects of bilateral STN deep brain stimulation (DBS) on motor and cognitive performance were investigated in a rat model of Parkinson disease (PD). After being trained in a choice reaction time (CRT) task, rats received bilateral injections of 6-hydroxydopamine (6-OHDA) into the striatum. One group of 6-OHDA animals was implanted bilaterally with stimulation electrodes at the level of the STN. Stimulations were performed at 130 Hz (frequency), 60 micros (pulse width), and varying amplitudes of 1, 3, 30, and 150 microA during the CRT task. Finally, rats were sacrificed and the brains processed for staining to determine the dopaminergic lesion (TH immunohistochemistry) and localization of the electrode tip (HE histochemistry). Bilateral 6-OHDA infusion significantly decreased (70%) the number of dopaminergic cells in the substantia nigra pars compacta (SNc) and increased motor time (MT), proportion of premature responding (PR), and reaction time (RT). Bilateral STN stimulation with an amplitude of 3 microA normalized 6-OHDA-induced deficits in PR and RT. Simulation with an amplitude of 30 microA reversed the lesion-induced deficits in MT and RT. Our data show for the first time that bilateral STN stimulation differentially affected the 6-OHDA-induced motor and cognitive deficits. This means that basal ganglia-thalamocortical motor and associative circuits responsible for specific motor and cognitive performance, which are processed through the STN, have unique physiological properties that can acutely and separately be modulated by specific electrical stimuli.

Animals↗
PubMed2005

Long-term effects of bilateral subthalamic nucleus stimulation in advanced Parkinson disease: a four year follow-up study.

In this study we aimed to investigate the effects of bilateral STN HFS in patients with advanced Parkinson disease (PD) at long-term, with a minimum follow-up of 4 years. Twenty patients (15 men, five women) were included, with a mean age of 60.9+/-8.1 years. Surgery was performed under local anesthesia. The target was defined on computerized tomography (CT). At 3 months, significant improvements were found on the total Unified Parkinson disease rating scale (UPDRS) III (motor) score, in the medication. off (from 42.3+/-9.3 to 19.5+/-6.4), as well as the medication on (from 18.6+/-12.1 to 10.1+/-5.9) phase. The UPDRS IVa (dyskinesias) and IVb (motor fluctuations) scores decreased significantly. At long-term follow-up, there were still significant improvements on the total UPDRS III motor score (from 42.3+/-9.3 to 24.2+/-13.2), as well as in all motor subscores, in the off phase, during stimulation. In the on phase, the only significant improvement was seen for rigidity. Complications included hypomania to mania in four patients. Our results indicate that HFS STN results in long-lasting improvement of the motor symptoms, ADL activities and functional performance in patients suffering from advanced PD. The stimulation induced behavioural changes need special consideration.

Activities of Daily Living↗
PubMed2005

The supraspinal network in the control of erection.

Penile erection is a complex event controlled by vascular, hormonal and neuronal systems. The neuronal system involved in erection is often divided into spinal and supraspinal networks. It is generally accepted that the spinal system directly controls erection and that the supraspinal network modulates this control mechanism through different ascending and descending pathways. In contrast to the spinal control of erection, relatively little is known about the supraspinal network. In the present review, the authors outline the supraspinal network involved in the control of penile erection. Firstly, the brain regions reported to be involved in erection are described and the brain circuit of erection is outlined. Subsequently, the neuromediators involved in erection are summarised. Finally, these data are discussed in the light of therapeutic possibilities in the management of erectile dysfunction by targeting the supraspinal system.

Animals↗
PubMed2004

Monopolar versus bipolar high frequency stimulation in the rat subthalamic nucleus: differences in histological damage.

The aim of the present study was to determine the effects of monopolar and bipolar high frequency stimulation (HFS) on histological damage and current flow using a commonly applied stimulus amplitude (300 microA). Bipolar HFS resulted in a large amount of histological damage whereas with monopolar HFS no damage was observed except for the electrode trajectory. Oscilloscopic readings confirmed that this was due to the application of twice as much current to the target with bipolar HFS. Our results demonstrate that there are differences in tissue damage dependent of polarity. In order to create a better comparison to the clinical condition, we suggest that the present rodent models for studying the effect of chronic HFS require further adjustment. This can be achieved by decreasing the present current densities to a level comparable to the human situation.

Animals↗