Neuroscience
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The common marmoset has emerged as a popular model in neuroscience research, in part due to its reproductive efficiency, genetic and neuroanatomical similarities to humans and the successful generation of transgenic lines. Stereotaxic procedures in marmosets are guided by 2D stereotaxic atlases, which are constructed with a limited number of animals and fail to account for inter-individual variability in skull and brain size. Here, we developed a frameless imaging-guided stereotaxic system that improves upon traditional approaches by using subject-specific registration of computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) data to identify a surgical target, namely the putamen, in two marmosets. ⋯ Injection of alpha-synuclein fibrils into the putamen triggered progressive neurodegeneration of the nigro-striatal system, a key feature of Parkinson's disease. Four months post-surgery, a PET scan found evidence of nigro-striatal denervation, supporting accurate targeting of the putamen during co-registration and subsequent surgery. Our results suggest that this approach, coupled with frameless stereotaxic neuronavigation, is accurate in localising surgical targets and can be used to assess endpoints for longitudinal studies.
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RAD6B is an E2 ubiquitin-conjugating enzyme, playing an important role in DNA damage repair, gene expression, senescence, apoptosis and protein degradation. However, the specific mechanism between ubiquitin and retinal degeneration requires more investigation. Pigment epithelium-derived factor (PEDF) has a potent neurotrophic effect on the retina, protecting retinal neurons and photoreceptors from cell death caused by pathological damage. ⋯ Affymetrix microarray analysis showed that the PEDF signal was changed in RAD6B deficient groups. The expression of γ-H2AX, β-Gal, P53, Caspase-3, P21 and P16 was increased significantly in retinas of RAD6B knockout (KO) mice. Our studies suggest that RAD6B and PEDF play an important role in the health of retina, whereas the absence of RAD6B accelerates the degeneration.
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Morphine rewarding properties are the main reasons for drug-craving in behaviors occurring during morphine addiction. It has been suggested that morphine addiction relies on signals to the mesolimbic dopamine system, although the mechanisms outside the dopaminergic system are still unclear. ⋯ Accordingly, optogenetic inhibition of DRN 5-HT neurons following morphine injection reversed conditioned place preference (CPP) during chronic morphine treatment. These findings aid our understanding of the new functions of the DRN 5-HT neurons for morphine rewarding effect and provide a potential approach for the treatment of morphine addiction.
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Human umbilical cord mesenchymal stem cells (UC-MSCs) transplantation has been shown to ameliorate intracerebral hemorrhage (ICH) in animal and clinical studies. We previously reported an easy one-step method to induce UC-MSCs into neurospheres with much enhanced neurogenic and angiogenic potential. In the present study, we further evaluated the neuro-protective effects of these UC-MSCs derived neurospheres (UC-MSCs-NS) using a murine collagenase induced ICH model. ⋯ However, long-term follow-up experiment showed delayed UC-MSCs-NS transplantation was superior to UC-MSCs transplantation alone in terms of increased neurogenic reconstitution. Our results suggest both UC-MSCs and UC-MSCs-NS can exert favorable effects in ICH therapy but the infusion of UC-MSCs-NS should avoid the super-early phase of ICH. We believe UC-MSCs derived neurospheres should be further exploited for chronic refractory neurological disorders such as chronic phase of stroke and various neurodegenerative disorders such as Alzheimer's disease.
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The endocannabinoid system within the periaqueductal grey (PAG) has been implicated in fear-conditioned analgesia (FCA), the profound suppression of pain upon re-exposure to a context previously paired with an aversive stimulus. Since the endocannabinoid and nociceptive systems exhibit sexual dimorphism, the aim of the present study was to assess possible sex differences in the expression of FCA, fear in the presence of nociceptive tone, and associated sex-dependent alterations in the endocannabinoid system within the PAG. Male and female Sprague-Dawley rats received footshock (10 × 1s; 0.4 mA; every 60 s) or no-footshock in a conditioning arena and 23.5 h later received intraplantar injection of formalin (2.5%) under brief isoflourane anaesthetic into the right hind paw. ⋯ There was no effect of fear conditioning on the levels of FAAH or CB1 receptor expression (CB1R) in the PAG of male or female formalin-treated rats. Non-fear-conditioned females had higher levels of CB1R and PPARγ expression than non-fear-conditioned male counterparts. In summary, our results provide evidence of sexual dimorphism in the expression of FCA and fear-related behaviours, and associated alterations in components of the endocannabinoid system and GABA within the PAG.