Neuroscience
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14-3-3s are a highly conserved protein family that plays important roles in cell survival and interact with several proteins implicated in Parkinson's disease (PD). Disruption of 14-3-3 expression and function has been implicated in the pathogenesis of PD. We have previously shown that increasing the expression level of 14-3-3θ is protective against rotenone and 1-methyl-4-phenylpyridinium (MPP(+)) in cultured cells. ⋯ Conversely, we investigated whether disrupting 14-3-3 function in transgenic mice expressing the pan 14-3-3 inhibitor difopein exacerbates MPTP-induced toxicity. We found that difopein expression promoted dopaminergic cell loss in response to MPTP treatment. Together, these findings suggest that 14-3-3θ overexpression promotes recovery of DA metabolites whereas 14-3-3 inhibition exacerbates neuron loss in the MPTP mouse model of PD.
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Transient receptor potential canonical channel-6 (TRPC6) forms Ca(2+)-permeable non-selective cation channels in neurons. Although TRPC6 plays an important role in neurite outgrowth and neuronal survival during development, TRPC6 expression profiles available to identify distinctive hippocampal neuronal damage and hippocampal excitability in epilepsy are less defined. ⋯ Furthermore, TRPC6 knockdown promoted programmed neuronal necrosis in dentate granule cells, but prevented it in CA1 and CA3 neurons following status epilepticus. The present data suggest for the first time that TRPC6 may inhibit seizure susceptibility and neuronal vulnerability in the rat DG.
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Spinal cord injury (SCI) that disrupts input from higher brain centers to the lumbar region of the spinal cord results in paraplegia, one of the most debilitating conditions affecting locomotion. Non-human primates have long been considered to be the most appropriate animal to model lower limb dysfunction. More recently, however, there has been a wealth of scientific information gathered in the rat regarding the central control of locomotion. ⋯ For each muscle under scrutiny, injections of Fluoro-Gold were then performed along the length of the MEP region. Targeting the MEPs gave rise to columns of motor neurons that span more spinal cord segments than previously reported. The importance of this study is discussed in terms of its application to gene therapy for SCI.
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Neuro-vascular rearrangement occurs in brain disorders, including epilepsy. Platelet-derived growth factor receptor beta (PDGFRβ) is used as a marker of perivascular pericytes. Whether PDGFRβ(+) cell reorganization occurs in regions of neuro-vascular dysplasia associated with seizures is unknown. ⋯ Our descriptive study points to microvascular-pericyte changes in the epileptic pathology. The possible link between PDGFRβ(+) cells, neuro-vascular dysplasia and remodeling during seizures is discussed.
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Cerebral venous sinus thrombosis (CVST) is a rare but life-threatening disease and an animal model for in-depth study of CVST is needed. This study aimed to develop a rat model suitable for studying clinically relevant aspects of CVST and investigating its dynamic pathophysiological changes during a 7-day period. ⋯ In this study, we describe a rat model that produces clinically relevant pathophysiology and pathology that will facilitate evaluation of therapeutic regimens for CVST. Furthermore, our results indicate a period of optimal clinical intervention for patients with CVST, which may reduce the probability of dependency and death.