Neuroscience
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Parkinson's disease (PD) is a progressive aging disorder that affects millions worldwide, thus, disease-modifying-therapies are urgently needed. PD pathology includes α-synuclein (aSyn) accumulation as synucleinopathy. Loss of GM1 gangliosides occurs in PD brain, which is modeled in GM2 synthase transgenic mice. ⋯ FTY720 treated GM2+/- brachial plexus sustained myelin associated protein levels and reduced aggregated aSyn and PSer129 aSyn levels. FTY720 increases brain derived neurotrophic factor (BDNF) and we noted increased BDNF in GM2+/- brachial plexus and cerebellum, which contribute to rotarod performance. These findings provide further support for testing low dose FTY720 in patients with PD.
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The ventrolateral periaqueductal gray matter (vlPAG) plays a critical role in the pathogenesis of migraine and few studies have shown that vlPAG might be involved in the pathophysiology of epilepsy. But its roles in epileptogenesis and comorbid relationship between migraine and epilepsy have never been reported. In this study, the impairments of vlPAG neuronal network during spontaneous recurrent seizure (SRS) development after status epilepticus (SE) were investigated, and the pain sensitivity as well as the SRS investigated after neurochemical lesion to vlPAG to determine the role of vlPAG in epileptogenesis and in migraine comorbidity with epilepsy. ⋯ On the other hand, neurochemical lesion to vlPAG enhanced frequency and duration of spontaneous seizure event and frequency of epileptiform inter-ictal spike discharges in electroencephalography (EEG), but decreased pain threshold in epileptic rats. This indicates an involvement of the pain regulating structure, vlPAG, in the pathogenesis of epilepsy. This may imply that vlPAG network alterations could be a possible underlying mechanism of the interactive comorbid relationship between epilepsy and migraine.
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Prescription opioid abuse is a serious public health issue. Recently, we showed that female and male Sprague-Dawley rats acquire conditioned place preference (CPP) to the mu opioid receptor agonist oxycodone. Anatomical analysis of the hippocampus from these rats unveiled sex differences in the opioid system in a way that would support excitation and opiate associative learning processes especially in females. ⋯ Oxycodone CPP females have: a) increases in ARC (activity regulated cytoskeletal-associated protein)-immunoreactivity (ir) in CA3 pyramidal cells; b) decreases in Npy (neuropeptide Y) gene expression in the medial hippocampus but higher numbers of NPY-containing hilar interneurons compared to males; c) increases in Crhr2 (corticotropin releasing factor receptor 2) expression in CA2/3; d) increases in Akt1 (AKT serine/threonine kinase 1) expression in medial hippocampus; and e) decreases in phosphorylated MAPK (mitogen activated protein kinase)-ir in CA1 and dentate gyrus. Oxycodone CPP males have: a) increases in Bdnf (brain derived-neurotrophic factor) expression, which is known to be produced in granule cells, relative to females; b) elevated Mapk1 expression and pMAPK-ir in the dentate hilus which harbors newly generated granule cells; and c) increases in CRHR1-ir in CA3 pyramidal cell soma. These sex-specific changes in plasticity, stress and kinase markers in hippocampal circuitry parallel previously observed sex differences in the opioid system after oxycodone CPP.
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Acute aerobic exercise induces short-term neuroplasticity, although it remains unknown whether biological sex and ovarian hormones influence this response. The present study investigated the effects of biological sex and ovarian hormones on short-term neuroplasticity induced by acute aerobic exercise. Young active adults (n = 17 males and n = 17 females; 21 ± 2 years) participated in two sessions in which transcranial magnetic stimulation (TMS) measures were acquired immediately before and after a 20-min bout of moderate-intensity cycling at 65-70% of maximal heart rate. ⋯ SIGNIFICANCE STATEMENT: Acute exercise induces short-term changes indicative of neuroplasticity within the primary motor cortex and corticospinal pathway. This research reveals that increases in corticospinal excitability and decreases in intracortical inhibition occur similarly in males and females, and that female hormones do not influence these changes. These findings may be used to assist with developing exercise interventions aimed at promoting neuroplasticity in both sexes.
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γ-Synuclein (γ-syn) is expressed by astrocytes in the human nervous system, and increased extracellularly in the brain and cerebrospinal fluid of individuals diagnosed with Alzheimer's disease. Upregulation of γ-syn also coincides with proliferation of glioblastomas and other cancers. In order to better understand regulation and function of extracellular γ-syn, primary human cortical astrocytes were treated with γ-syn conditioned media at various physiological concentrations (50, 100, 150 nM) after cell synchronization. ⋯ Further analysis of cell cycle markers with immunocytochemistry of BrdU and Ki67 after treatment with 100 nM γ-syn confirmed increased initial cell proliferation and decreased non-proliferating cells. Western blot analysis demonstrated increased γ-syn levels after 100 nM treatment at 24 and 48 h, and increased pro-BDNF, mature BDNF and cell viability at 48 h. The results demonstrate that γ-syn internalization by human cortical astrocytes causes upregulation of the cell cycle, followed by subsequent BDNF expression and release.