Neuroscience
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During cerebral ischemia, brain lactate concentration increases, and astrogliosis is triggered. Herein, we investigated lactate's role in astrogliosis and explored the functions of lactate-activated astrocytes in vitro. In rat models of cerebral ischemia, we observed increased glial fibrillary acidic protein (GFAP) expression, reflecting astrogliosis, and increased lactate levels in the ischemic brain region. ⋯ Genes upregulated by lactate treatment included those regulating astrogliosis and axon guidance. Consistently, lactate-treated astrocytes induced neuronal outgrowth upon coculture. Our results suggest that lactate promotes reactive astrogliosis and confers axon guidance potential to astrocytes under OGD.
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The interconnectivity between brain development and the immune system has become an area of interest for many neuroscientists. However, to date, a limited number of known immune mediators of the peripheral nervous system (PNS) have been found to influence the development of the central nervous system (CNS). FOXP3 is a well-established mediator of regulatory T-cells in the PNS. ⋯ In the PNS, Foxp3 protein levels were low embryonically and increased steadily over the life of the animal with maximal levels reached in adulthood. Patterns observed for both the PNS and CNS were similar in males and females across all developmental timepoints. Our novel findings have implications for understanding how the neural immune system impacts neurodevelopmental disorders such as autism and schizophrenia.
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The bacterial exoenzyme C3 transferase (C3) irreversibly inhibits RhoA GTPase leading to stimulation of axonal outgrowth in injured neurons. C3 has been used successfully in models of neurotrauma and shows promise as an option to support cell survival and axonal growth of dopaminergic (DA) neurons in Parkinson's disease (PD) cell therapy. Whether the continuous expression of C3 in DA neurons is well-tolerated is unknown. ⋯ To evaluate the impact of C3 expression on striatal terminals of the nigrostriatal pathway, we compared the rotational behavior of wildtype mice injected unilaterally with either C3 or 6-hydroxydopamine (6-OHDA). Mice injected with C3 exhibited similar ipsiversive rotations to the site of injection in comparison to control mice injected with EYFP and significantly fewer ipsiversive rotations compared to 6-OHDA lesioned mice. Non-significant difference between C3 and EYFP controls in behavioral and histological analyses demonstrate that transduced DA neurons express C3 continuously without apparent adverse effects, supporting the use of C3 in efficacy studies targeting DA neurons.
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During prolonged dehydration, body fluid homeostasis is challenged by extracellular fluid (ECF) hyperosmolality, which induce important functional changes in the hypothalamus, in parallel with other effector responses, such as the activation of the local renin-angiotensin system (RAS). Therefore, in the present study we investigated the role of sodium-driven ECF hyperosmolality on glial fibrillary acid protein (GFAP) immunoreactivity and protein expression, membrane capacitance, mRNA expression of RAS components and glutamate balance in cultured hypothalamic astrocytes. Our data show that hypothalamic astrocytes respond to increased hyperosmolality with a similar decrease in GFAP expression and membrane capacitance, indicative of reduced cellular area. ⋯ Incubation with hypertonic solution also decreases the immunoreactivity to the membrane glutamate/aspartate transporter (GLAST) as well as tritiated-aspartate uptake by astrocytes. This latter effect is completely restored to basal levels when astrocytes previously exposed to hypertonicity are incubated under isotonic conditions. Together with a direct effect on two important local signaling systems (glutamate and RAS), these synaptic rearrangements driven by astrocytes may accomplish for a coordinated increase in the excitatory drive onto the hypothalamic neurosecretory system, ultimately culminating with increased AVP release in response to hyperosmolality.
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The basal nucleus of Meynert (BNM) shows structural abnormalities in Parkinson's disease with mild cognitive impairment (PD-MCI). However, it is yet unknown whether functional connectivity (FC) in the BNM (BNM-FC) is altered in patients with PD-MCI. Therefore, in this study, we compared the BNM-FC of patients with PD-MCI and PD patients with normal cognition (PD-NC), to evaluate the relationship between the observed differences of BNM-FC and neuropsychological test scores. ⋯ We found that 86.36% subjects were correctly classified based on the BNM-FC using the leave-one-out cross-validation (LOOCV) method, with a sensitivity of 90.91% and specificity of 81.82%. Our study provides new insights into the neural basis of cognitive dysfunction in PD patients. We also found that BNM-FC can be an effective feature to distinguish PD-MCI from PD-NC.