Although the medial subdivision of the central nucleus of the amygdala (CeM) and serotonin-1A (5-HT1A) receptors are involved in the regulation of anxiety, their roles in Parkinson's disease (PD)-associated anxiety are still unknown. Here we assessed the importance of CeM 5-HT1A receptors for anxiety in rats with unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle (MFB). The lesion induced anxiety-like behaviors, increased the firing rate and burst-firing pattern of CeM γ-aminobutyric acid (GABA) neurons, as well as decreased dopamine (DA) levels in the striatum, medial prefrontal cortex (mPFC), amygdala and ventral part of hippocampus (vHip). Intra-CeM injection of the selective 5-HT1A receptor agonist 8-OH-DPAT produced anxiolytic effects in the lesioned rats, and decreased the firing rate of CeM GABAergic neurons in two groups of rats. Compared to sham-operated rats, the duration of the inhibitory effect on the firing rate of GABAergic neurons was shortened in the lesioned rats. The injection increased DA levels in the mPFC and amygdala in two groups of rats and the vHip in the lesioned rats, and increased 5-HT level in the lesioned rats, whereas it decreased NA levels in the mPFC in two groups of rats and the vHip in the lesioned rats. Moreover, the mean density of 5-HT1A receptor and GABA double-labeled neurons in the CeM was reduced after the lesioning. These results suggest that activation of CeM 5-HT1A receptor produces anxiolytic effects in the 6-OHDA-lesioned rats, which involves decreased firing rate of the GABAergic neurons, and changed monoamine levels in the limbic and limbic-related brain regions.
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http://dx.doi.org/10.1016/j.neuropharm.2015.03.007 | DOI Listing |
Int Immunopharmacol
December 2024
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sinai University- Arish Branch, Arish 45511, Egypt.
Unlabelled: Despite a deep understanding of Parkinson's disease (PD) and levodopa-induced dyskinesia (LID) pathogenesis, current therapies are insufficient to effectively manage the progressive nature of PD or halt LID. Growing hypotheses suggested the NOD-like receptor 3 (NLRP3) inflammasome and orphan nuclear receptor-related 1 (Nurr1)/glycogen synthase kinase-3β (GSK-3β) and peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α)/sirtuin 3 (SIRT3) pathways as potential avenues for halting neuroinflammation and oxidative stress in PD.
Aims: This study investigated for the first time the neuroprotective effect of canagliflozin against PD and LID in rotenone-intoxicated rats, emphasizing the crosstalk among the NLRP3/caspase-1 cascade, PGC-1α/SIRT3 pathway, mammalian target of rapamycin (mTOR)/beclin-1, and Nurr1/β-catenin/GSK-3β pathways as possible treatment strategies in PD and LID.
PLoS One
December 2024
Department of Neurological Surgery, UCSF, San Francisco, CA, United States of America.
Experimental rat models of stroke and hemorrhage are important tools to investigate cerebrovascular disease pathophysiology mechanisms, yet how significant patterns of functional impairment induced in various models of stroke are related to changes in connectivity at the level of neuronal populations and mesoscopic parcellations of rat brains remain unresolved. To address this gap in knowledge, we employed two middle cerebral artery occlusion models and one intracerebral hemorrhage model with variant extent and location of neuronal dysfunction. Motor and spatial memory function was assessed and the level of hippocampal activation via Fos immunohistochemistry.
View Article and Find Full Text PDFPharmacol Biochem Behav
December 2024
Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Boulevard Juriquilla, No. 3001, C.P. 76230, Querétaro, Mexico.
Pain is one of the principal non-motor symptoms of Parkinson's disease (PD), negatively impacting the patient's quality of life. This study aimed to demonstrate whether an effective dose of pramipexole (PPX) can modulate the NF-κB/p-p65 activation in glial cells (astrocytes and microglia) and diminish the hypersensitivity (allodynia and hyperalgesia) in male Wistar rats with PD. For this, 2 μl of 6-hydroxydopamine (6-OHDA, 8 μg/μL/0.
View Article and Find Full Text PDFiScience
December 2024
Department of Neuroscience, Shriners Hospitals Pediatric Research Center, Center for Neural Rehabilitation and Repair, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Skilled forelimb patterning is regulated by the corticospinal tract (CST) with support from brainstem regions. When the CST is lesioned, there is a loss of forelimb function; however, if indirect pathways remain intact, rehabilitative training can facilitate recovery. Following spinal cord injury, rehabilitation is thought to enhance the reorganization and plasticity of spared supraspinal-propriospinal circuits, aiding functional recovery.
View Article and Find Full Text PDFSub-anesthetic ketamine has been demonstrated to reduce abnormal involuntary movements (AIMs) in preclinical models of L-DOPA-induced dyskinesia (LID) and retrospective Parkinson's disease case reports. In this study, we examined the effects on L-DOPA-induced dyskinesia of two statins alone and in combination with ketamine in unilateral 6-hydroxydopamine-lesioned male rats, the standard preclinical LID model. Sub-anesthetic ketamine attenuated the development of AIMs, while lovastatin only showed anti-dyskinetic activity at the beginning of the priming but did not prevent the development of LID.
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