Neuroscience
-
Ontogenetic life and stress can have different effects on the nerve growth factor (NGF) and its tyrosine kinase receptor A (TrkA) in the structures of the limbic system. This study aimed to explore the influence of two different stressors, acute and chronic exposure to forced swim (FS) stress or high-light open-field (HL-OF) stress, on cells containing NGF and TrkA. Immunofluorescence staining was used to reveal the density of NGF and TrkA immunoreactive (ir) cells in the paraventricular nucleus (PVN) of the hypothalamus or hippocampal subfields CA1, CA3 and dentate gyrus (DG) in adult (postnatal day 90; P90) and aged (P720) rats. ⋯ Despite lack of change in the density of NGF-ir and TrkA-ir cells between P90 and P720 non-stressed rats, a significant age-related decrease in NGF-ir and TrkA-ir cells in the PVN of FS- and HL-OF-stressed rats was noted. However, in the hippocampus, an age-related decrease in NGF-ir or TrkA-ir cells was observed in all rats except acute FS-stressed rats. The changes are possibly associated with involutional aging processes caused by insufficient control of hypothalamic-pituitary-adrenal (HPA) axis functioning in P720 rats and may contribute to disturbances in NGF signaling.
-
Dysregulation of sphingolipid metabolism has been shown to trigger the pathophysiology of many neurodegenerative disorders. The present study focuses on the role of one of the two sphingosine kinases, Sphk2 and its metabolite sphingosine-1-phosphate (S1P) signaling in Parkinson's disease (PD). Our study indicated a marked down regulation of Sphk2 expression in the substantia nigra region of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and in the cellular PD model. ⋯ It was also observed that levels of ROS were significantly decreased in the MPP(+)-treated cells in the presence of exogenous S1P. Our study also demonstrated that S1P exerted its protective effect through the S1P1 receptor. Taken together, these results show that Sphk2/S1P has an important role to play in the survival of the dopaminergic neurons, in the pathogenesis of PD.
-
Besides motor disturbances, other symptoms found in the early stage of Parkinson's disease (PD) are deficits in both learning and memory. The nigro-striatal-cortical pathway is affected in this pathology, with this neuronal circuit involved in cognitive processes such as spatial working memory (SWM). However, cognitive dysfunction appears even when the patients are receiving L-DOPA treatment. ⋯ Nitrite levels and immunoreactivity of 3-Nitrotyrosine (3-NT), Inducible Nitric Oxide Synthase (iNOS), Glial Fibrillary Acidic Protein (GFAP), and Tyrosine Hydroxylase (TH) were evaluated in the substantia nigra pars compacta, the dorsal striatum and the medial prefrontal cortex. Our results show that chronic L-DOPA administration in rats with intra-nigral 6-OHDA-lesion caused significant increases in SWM deficit, nitrite levels and the immunoreactivity of 3-NT, iNOS and GFAP in the nigro-striatal-cortical pathway. These facts suggest that as L-DOPA can induce NS in rats with dopaminergic intra-nigral lesion, it could play a key role in the impairment of the SWM, and thus can be considered as a toxic mechanism that induces cognitive deficit in PD patients.
-
Studies demonstrated that chronic high-dose homocysteine administration induced learning and memory impairment in animals. Atractylenolide III (Aen-III), a neuroprotective constituent of Atractylodis macrocephalae Koidz, was isolated in our previous study. In this study, we investigated potential benefits of Aen-III in preventing learning and memory impairment following chronic high-dose homocysteine administration in rats. ⋯ Moreover, Aen-III protected primary cultured neurons from apoptotic death induced by homocysteine treatment. This study provides the first evidence for the neuroprotective effect of Aen-III in preventing learning and impairment induced by chronic administration of homocysteine. Aen-III may have therapeutic potential in treating homocysteine-mediated cognitive impairment and neuronal injury.
-
Anesthetic doses of ketamine induce apoptosis, as well as gene expression of activity-dependent neuroprotective protein (ADNP), a putative homeodomain transcription factor in rat pups (P7). This study investigated if ketamine induced ADNP protein in a dose-dependent manner in vitro and in vivo using primary cultures of cortical neurons and neonatal pups (P7). In vivo immunohistochemistry demonstrated a sub-anesthetic dose of ketamine increased ADNP in the somatosensory cortex (SCC) which was previously identified to be damaged by repeated exposure to anesthetic doses of ketamine. ⋯ Primary cultures of cortical neurons treated with ketamine (10 μM-10mM) at 3 days-in vitro (3 DIV) displayed a concentration-dependent decrease in expanded growth cones. Furthermore, neuronal production and localization of ADNP varied as a function of both ketamine concentration and length of exposure. Taken together, these data support the model that ADNP induction may be partially responsible for the efficacy of a low-dose ketamine pre-treatment in preventing ketamine-induced neuronal cell death.